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The childhood immunization schedule is well known and generally well implemented in developed countries. For various reasons, the same is not true of vaccines aimed at preventing infections in adults, in which vaccination coverage is incomplete and generally very deficient. In order to assess the situation of adult vaccination in Spain, the Fundación de Ciencias de la Salud has brought together a series of experts in different fields, including doctors, nurses, representatives of patient associations, health managers and economists, health authorities and journalists to deal with this issue. The format was that of a round table in which a series of questions previously formulated by the coordinators were to be answered and debated. The document presented is not an exhaustive review of the topic, nor is it intended to make recommendations, but only to give a multidisciplinary opinion on topics that could be particularly debatable or controversial. The paper reviews the main vaccine-preventable adult diseases, their clinical and economic impact, the possibilities of reducing them with vaccination programmes and the difficulties in carrying them out. The role of nursing, pharmacy services, patient associations and the health administration itself in changing the current situation was discussed. Prospects for new vaccines were discussed and we speculated on the future in this field. Finally, particularly relevant ethical aspects in decision-making regarding vaccination were discussed, which must be faced by both individuals and states. We have tried to summarize, at the end of the presentation of each question, the environment of opinion that was agreed with all the members of the table., (©The Author 2019. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

The study aims to isolate the cellulose-degradation bacteria that produce the cellulase enzyme as well as the production of SCP protein from Ramadi city soils and to obtain efficient local bacterial isolates in production and efficient isolation was selected in the production of cellulase enzyme and single cell protein which is Bacillus subtillis bacteria tested the efficiency of the isolated isolation to produce the enzyme and single cell protein. The cell using local media contains the paper waste available in the environment and contaminated with it. Initial transactions were made for this paper waste and these factors included (heating to boiling point, dilute sulfuric acid and dilute sodium hydroxide). The paper waste used included the white cardboard, yellow cardboard and white paper Which was used as a single source of carbon and energy, after testing the waste paper used, it was found that the white cardboard treated with heating gave the best production of the cellulase enzyme and single-cell protein. The bacterial isolation used showed the best growth and gave the highest production of the enzyme and the single cell protein at pH 7, while the best temperature for the production of the enzyme was 45 ° C. The optimum temperature for the production of the single cell protein was 40 ° C. As for the carbon concentration, which is the white cardboard treated with heating, it was better to produce than Concentration is 2%. As for the production of single cell protein, the highest output at concentration was 4%. The best bacterial vaccine size for enzyme production was 3 ml / 100 ml medium. As for the production of single cell protein, the size of the inoculum gave 1.5 ml / 100 ml the best production. The addition of the organic nitrogen source (urea) gave a clear increase in enzyme production and single cell protein, and when adding 0.5 g urea / 100 mL medium. Finally, the results showed that the best period duration to obtain the highest cellulase enzyme production was after 96 hours, while it was found that the best production of single-cell protein was after 24 hours incubation. [ABSTRACT FROM AUTHOR]

Q fever (caused by Coxiella burnetii) is a serious zoonotic disease that occurs almost worldwide. Occupational contact with animals increases the risk of exposure, and Q fever vaccination is recommended for veterinary workers in Australia. This study aimed to investigate C. burnetii seroprevalence among unvaccinated veterinary workers in Australia and determine factors associated with a positive serological result. During 2014 and 2015, convenience sampling at veterinary conferences and workplace vaccination clinics was undertaken. Participants completed a questionnaire and provided a blood sample for C. burnetii serology. Participants were predominantly veterinarians (77%), but veterinary support staff, animal scientists, and administration workers also participated. Blood samples (n = 192) were analysed by an immunofluorescence assay and considered positive where the phase I or phase II IgG titre was ≥1/50. Seroprevalence was 19% (36/192; 95% CI 14%-25%). A positive serological result was significantly associated with (a) working in outer regional/remote areas (odds ratio [OR] 6.2; 95% CI 1.9-20.8; reference = major cities; p = .009) and (b) having spent more than 50% of total career working with ruminants (OR 4.8; 95% CI 1.7-13.5; reference = <15% of career; p = .025). These findings confirm an increased risk of exposure to C. burnetii compared to the general population, providing new evidence to support Q fever vaccination of veterinary workers in Australia., (© 2019 Blackwell Verlag GmbH.)

The use of antibiotics has enabled the successful treatment of bacterial infections, saving the lives and improving the health of many patients worldwide. However, the emergence and spread of antimicrobial resistance (AMR) has been highlighted as a global threat by different health organizations, and pathogens resistant to antimicrobials cause substantial morbidity and death. As resistance to multiple drugs increases, novel and effective therapies as well as prevention strategies are needed. In this Review, we discuss evidence that vaccines can have a major role in fighting AMR. Vaccines are used prophylactically, decreasing the number of infectious disease cases, and thus antibiotic use and the emergence and spread of AMR. We also describe the current state of development of vaccines against resistant bacterial pathogens that cause a substantial disease burden both in high-income countries and in low- and medium-income countries, discuss possible obstacles that hinder progress in vaccine development and speculate on the impact of next-generation vaccines against bacterial infectious diseases on AMR.

Troponin T, which is a biomarker of cardiovascular disease, is vital for acute myocardial infarction (AMI). AMI is the most well-known cause of death in the world. In the present work, we designed a novel immunosensor using disposable, cheap, and very conductive graphite paper electrodes (GP). The proposed immunosensor was modified with hydrochloric acid (HCl) for immobilization of anti-TnT antibody. After carboxyl group formation on the surface, the GP electrodes were incubated with EDC/NHS pair as a cross-linker. Electrochemical impedance spectroscopy (EIS), single frequency impedance (SFI), cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques were used for electrochemical characterization of the label-free immunosensor. Furthermore, the fabrication process of the proposed immunosensor was examined by using scanning electron microscopy (SEM). The proposed electrochemical immunosensor had a wide detection range (0.5 fg - 1000 fg/mL), and low limit of detection (LOD) and low limit of quantification (LOQ) at 1.28 fg/mL and 4.29 fg/mL, respectively. The designed immunosensor exhibited very good sensitivity, reproducibility, repeatability, reusability and long storage life. Additionally, the immunosensor was successfully applied to detection of TnT in human serum. Image 1 • Disposable graphite paper electrodes were firstly used to detection TnT antigen for a novel immunosensor system. • TnT immunosensor exhibited high analytical performance with a linear range 0.5 fg/mL – 1000 fg/mL and low detection limit (1.28 fg/mL). [ABSTRACT FROM AUTHOR]

Vaccination has become a widely used method to induce immune protection against microbial pathogens, including viral and bacterial microorganisms. Both humoral and cellular immunity serve a critical role in neutralizing and eliminating these pathogens. An effective vaccine should be able to induce a long-lasting immune memory response. Recent investigations on different subsets of T cells have identified a new subset of T cells using multi-parameter flow cytometry, which possess stem cell-like properties and the ability to mount a rapid immune response upon re-exposure to antigens known as stem cell-like memory T cells (T SCM ). One of the major challenges with current vaccines is their limited ability to maintain long-term memory in the adaptive immune system. Recent evidence suggests that a specific subgroup of memory T cells has the unique ability to retain their longevity for up to 25 years, as observed in the case of the yellow fever vaccine. Therefore, in this study, we tried to explore and discuss the potential role of this new T cell memory subset in the development of viral and bacterial vaccines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mucosal vaccination presents a promising complement to parenteral vaccination. Bacterium-like particles (BLPs), peptidoglycan structures prepared from lactic acid bacteria, are explored as potential nasal vaccine adjuvants for respiratory infections. To date, studies on BLP-adjuvanted nasal vaccines against intestinal infections have remained limited. In this study, we demonstrated the efficacy of intranasal BLP-adjuvanted vaccination in controlling intestinal infections using the Citrobacter rodentium (C. rodentium) model in C57BL/6 mice. Intranasal vaccination of Intimin, an adhesin critical for intimate bacterial adhesion to colonic epithelial cells, combined with BLP (BLP+I) elicited robust Intimin-specific intestinal secretory IgA production, reduced bacterial load in feces and almost completely inhibited colonic hyperplasia, a characteristic symptom of C. rodentium infection in mice. Conversely, parenteral vaccination with Alhydrogel-adjuvanted Intimin failed to induce intestinal Intimin-specific IgA production, resulting in poor protection against C. rodentium infection. This underscores the pivotal role of mucosal IgA responses elicited by intranasal immunization in its protective efficacy. As this study did not delineate the precise protective mechanism conferred by BLP+I intranasal immunization against C. rodentium infection, further elucidation of the mechanisms underlying intranasal BLP+I immunization is required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aeromonas salmonicida is one of the most prevalent pathogens that causes huge economic losses to aquaculture. Effective vaccination is the first choice for preventing infection. Bacterial ghost (BG), an empty bacterial shell devoid of cytoplasm, is a promising vaccine antigen with distinct advantages. Herein, we established strategies for producing a substantial yield of A. salmonicida ghost (ASG) and investigated the immune-protective properties of it. As a result, 2.84 mg/ml NaOH was discovered to be capable of inducing considerable amounts of ASG. Furthermore, the ASG vaccine elicited adaptive immunity in turbots after rapid activation of innate immunity. Even though formalin-killed cells (FKC) produced a few more antibodies than ASG, ASG ultimately provided a much stronger immune protection effect because it strengthened cellular immunity, with a relative percentage survival (RPS) of 50.1 % compared to FKC. These findings demonstrated that ASG effectively activated cell-mediated immunity, which helped get rid of microorganisms inside cells. Therefore, this study presented novel perspectives for future research on furunculosis vaccine products based on ASG as an antigen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

An effective prophylactic vaccine for prevention of Neisseria gonorrhoeae infection would have a major impact on sexual and reproductive health worldwide. Interest in developing gonorrhoea vaccines is growing due to the reported high rates of N. gonorrhoeae infections globally, and the threat of antimicrobial resistance. Several gonorrhoea vaccine candidates are currently under evaluation and various mathematical models have been used to assess the potential population-level impact a gonorrhoea vaccine may have once available. Here we review key aspects of gonorrhoea vaccine mathematical modelling studies, including model structures, populations considered, and assumptions used as well as vaccine characteristics and implementation scenarios investigated. The predicted vaccine impact varied between studies, ranging from as little as ∼17 % reduction in N. gonorrhoeae prevalence after 30 years up to 100 % reduction after 5 years. However, all studies predicted that even a partially effective gonorrhoea vaccine could have a substantial impact in reducing N. gonorrhoeae prevalence or incidence, particularly when high coverage is achieved within either important risk groups or the overall sexually active population. As expected, higher vaccine efficacy against acquisition of N. gonorrhoeae and longer duration of protection were linked to greater reductions in infections. A vaccine that alters onward transmission could also substantially reduce infections. Several gaps and research needs have been identified by researchers in the field and via this narrative literature review. For example, future modelling to inform gonorrhoea vaccine development and implementation should consider additional populations that are at high risk of N. gonorrhoeae infection, especially in low- and middle-income settings, as well as the impact of vaccination on the potential adverse sexual and reproductive health outcomes of infection. In addition, more detailed and robust epidemiological, biological, and behavioural data is needed to enable more accurate and robust modelling of gonorrhoea vaccine impact to inform future scientific and public health decision-making., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Thilini Padeniya reports financial support was provided by National Institutes of Health. Kate Seib reports financial support was provided by National Institutes of Health. Kate Seib reports financial support was provided by National Health and Medical Research Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neisseria gonorrhoeae infection (gonorrhoea) is a global public health challenge, causing substantial sexual and reproductive health consequences, such as infertility, pregnancy complications and increased acquisition or transmission of HIV. There is an urgency to controlling gonorrhoea because of increasing antimicrobial resistance to ceftriaxone, the last remaining treatment option, and the potential for gonorrhoea to become untreatable. No licensed gonococcal vaccine is available. Mounting observational evidence suggests that N. meningitidis serogroup B outer membrane vesicle-based vaccines may induce cross-protection against N. gonorrhoeae (estimated 30%-40% effectiveness using the 4CMenB vaccine). Clinical trials to determine the efficacy of the 4CMenB vaccine against N. gonorrhoeae are underway, as are Phase 1/2 studies of a new gonococcal-specific vaccine candidate. Ultimately, a gonococcal vaccine must be accessible, affordable and equitably dispensed, given that those most affected by gonorrhoea are also those who may be most disadvantaged in our societies, and most cases are in less-resourced settings. This vaccine value profile (VVP) provides a high level, holistic assessment of the current data to inform the potential public health, economic and societal value of pipeline vaccines. This was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations. All contributors have extensive expertise on various elements of the N. gonorrhoeae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using published data obtained from peer-reviewed journals or reports., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JJO reports financial support from the World Health Organization and Australian National Health and Medical Research Foundation. Some of the authors are present or former staff members of the World Health Organization. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) and 4.95 million (95% UI: 3.62-6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K.pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K.pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K.pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ziyaad Dangor reports financial support was provided by Bill & Melinda Gates Foundation. Ziyaad Dangor reports financial support was provided by World Health Organization. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Community-acquired pneumonia often stems from the macrolide-resistant strain of Mycoplasma pneumoniae, yet no effective vaccine exists against it., Methods: This study proposes a vaccine-immunoinformatics strategy for Mycoplasma pneumoniae and other pathogenic microbes. Specifically, dominant B and T cell epitopes of the Mycoplasma pneumoniae P30 adhesion protein were identified through immunoinformatics method. The vaccine sequence was then constructed by coupling with CTLA-4 extracellular region, a novel molecular adjuvant for antigen-presenting cells. Subsequently, the vaccine's physicochemical properties, antigenicity, and allergenicity were verified. Molecular dynamics modeling was employed to confirm interaction with TLR-2, TLR-4, B7-1, and B7-2. Finally, the vaccine underwent in silico cloning for expression., Results: The vaccine exhibited both antigenicity and non-allergenicity. Molecular dynamics simulation, post-docking with TLR-2, TLR-4, B7-1, and B7-2, demonstrated stable interaction between the vaccine and these molecules. In silico cloning confirmed effective expression of the vaccine gene in insect baculovirus vectors., Conclusion: This vaccine-immunoinformatics approach holds promise for the development of vaccines against Mycoplasma pneumoniae and other pathogenic non-viral and non-bacterial microbes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Achromobacter xylosoxidans is an aerobic, catalase-positive, non-pigment-forming, Gram-negative, and motile bacterium. It potentially causes a wide range of human infections in cystic fibrosis and non-cystic fibrosis patients. However, developing a safe preventive or therapeutic solution against A. xylosoxidans remains challenging. This study aimed to construct an epitope-based vaccine candidate using immunoinformatic techniques. A. xylosoxidans was isolated from an auto workshop in Lahore, and its identification was confirmed through 16S rRNA amplification and bioinformatic analysis. Two protein targets with GenBank accession numbers AKP90890.1 and AKP90355.1 were selected for the vaccine construct. Both proteins exhibited antigenicity, with scores of 0.757 and 0.580, respectively and the epitopes were selected based on the IC50 value using the ANN 4.0 and NN-align 2.3 epitope prediction method for MHC I and MHC II epitopes respectively and predicted epitopes were analyzed for antigenicity, allergenicity and pathogenicity. The vaccine construct demonstrated structural stability, thermostability, solubility, and hydrophilicity. The vaccine produced 250 B-memory cells per mm 3 and approximately 16,000 IgM + IgG counts, indicating an effective immune response against A. xylosoxidans. Moreover, the vaccine candidate interacted stably with toll-like receptor 5, a pattern recognition receptor, with a confidence score of 0.98. These results highlight the potency of the designed vaccine candidate, suggesting its potential to withstand rigorous in vitro and in vivo clinical trials. This epitope-based vaccine could serve as the first preventive immunotherapy against A. xylosoxidans infections, addressing this bacterium's health and financial burdens. The findings demonstrate the value of employing immunoinformatic tools in vaccine development, paving the way for more precise and tailored approaches to combating microbial threats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Pseudomoans plecoglossicida has been identified as a fish pathogen since 2000 and has caused serious infections in cultured Large Yellow Croakers Larimiththys crocea in coastal eastern China during recent years., Methods: Published literatures of this pathogen have been reviewed., Result: Several strains with high genomic similarity have been isolated and identified; the bacteria induce natural infection at lower water temperatures (12.0-25.5°C) and induce numerous granulomas and nodules in the visceral organs of croakers. Researchers have investigated the epidemiology of P. plecoglossicida infection, identified major virulence factors, searched for pathogenic genes, analyzed host-pathogen interactions, and endeavored to develop efficient vaccines., Conclusion: This paper provides an overview of these research advances to elucidate the virulence mechanisms of the pathogen and to promote vaccine development against infection., (© 2024 American Fisheries Society.)

Clostridium perfringens is ubiquitously distributed and capable of secreting toxins, posing a significant threat to animal health. Infections caused by Clostridium perfringens, such as Necrotic Enteritis (NE), result in substantial economic losses to the livestock industry annually. However, there is no effective commercial vaccine available. Hence, we set out to propose an effective approach for multi-epitope subunit vaccine construction utilizing biomolecules. We utilized immunoinformatics to design a novel multi-epitope antigen against C. perfringens (CPMEA). Furthermore, we innovated novel bacterium-like particles (BLPs) through thermal acid treatment of various Lactobacillus strains and selected BLP23017 among them. Then, we detailed the structure of CPMEA and BLPs and utilized them to prepare a multi-epitope vaccine. Here, we showed that our vaccine provided full protection against C. perfringens infection after a single dose in a mouse model. Additionally, BLP23017 notably augmented the secretion of secretory immunoglobulin A (sIgA) and enhanced antibody production. We conclude that our vaccine possess safety and high efficacy, making it an excellent candidate for preventing C. perfringens infection. Moreover, we demonstrate our approach to vaccine construction and the preparation of BLP23017 with distinct advantages may contribute to the prevention of a wider array of diseases and the novel vaccine development., Competing Interests: Declaration of competing interest The authors of this paper declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine. [ABSTRACT FROM AUTHOR]

In this study, postsmolt male Atlantic salmon, previously identified as low responders (LRs) or high responders (HRs) based on poststress cortisol levels, had their head kidney and liver sampled at 12°C and 20°C before injection (time 0) and after injection (i.e., at 12- and 24-h postinjection, respectively) with either Forte Micro (a multivalent vaccine containing bacterin, to capture peak antibacterial responses) or an equal volume of PBS. Quantitative real-time PCR (qPCR) was then used to measure the expression of 15 biomarker genes in the head kidney and 12 genes in the liver at each temperature/sampling point. Target transcripts were chosen that were related to growth, stress, and innate antibacterial immune responses. Many temperature, phenotype, and injection effects were found for individual genes within these three broad categories, and multivariate statistical analyses (i.e., principal component analysis and permutational multivariate analysis of variance) were used to look for overall patterns in transcript expression. These analyses revealed that HR salmon at 20°C mounted a more robust response (P < 0.05) for the 10 head kidney immune-related transcripts when injected with Forte Micro than LR salmon. In contrast, the seven liver stress-related transcripts displayed a greater response (P = 0.057) in LR versus HR fish with Forte Micro at 12°C. Overall, although this research did find some differences between LR and HR fish, it does not provide strong (conclusive) evidence that the selection of a particular phenotype would have major implications for the health of salmon over the temperature range examined. NEW & NOTEWORTHY This is the first paper to describe the impact of both temperature and bacterial stimulation on head kidney and liver transcript expression in Atlantic salmon characterized as LRs versus HRs. Notably, we found that HR salmon at 20°C mounted a more robust innate antibacterial immune response than LR salmon. In addition, LR fish at 12°C may (P = 0.057) exhibit higher expression of stress-related transcripts in response to vaccine injection relative to HR fish. [ABSTRACT FROM AUTHOR]

Currently, the best method to well control the spread of COVID-19 without severe mental health problems is to reach herd immunity. Therefore, the vaccination rate of the COVID-19 vaccine is critical. Among the populations, children are the vulnerable ones to get vaccinated; therefore, it is important to assess parents' and guardians' willingness to have their children vaccinated. The present systematic review and meta-analysis synthesized evidence to estimate the parents' acceptance rate of COVID-19 vaccination toward their children. Additionally, factors explaining the acceptance rate were investigated. Four academic databases (PubMed, Scopus, Web of Science, and ProQuest) together with Google Scholar were searched, and the references of the included publications were searched as well. Using the PECO-S framework (population, exposure, comparison, outcome, and study design), observational studies of cross-sectional, cohort, or case-control studies were included. The outcome was parents' or guardians' willingness to let their children be vaccinated. The studies included in the present review were restricted to English and peer-reviewed papers published between December 2019 and July 2022. A total of 98 papers across 69 different countries with 413,590 participants were included. The mean age of the parents was 39.10 (range: 18–70) years and that of their children was 8.45 (range: 0–18) years. The pooled estimated prevalence of parental acceptance to vaccinate their children with the COVID-19 vaccine was 57% (98 studies, 95% CI: 52–62%, I2: 99.92%, τ2: 0.06). Moreover, data collection time was a significant factor explaining parental willingness in the multivariable meta-regression, with a 13% decrease in parental willingness by each month increase in time, explaining 11.44% of variance. Qualitative synthesis results showed that parents' COVID-19 vaccine knowledge, trust in theCOVID-19 vaccine, and facilitators in vaccination (e.g., low cost, good vaccine accessibility, and government incentive) were significant factors for higher willingness, while mental health problems (e.g., having worries and psychological distress) were significant factors for lower willingness. Given that the acceptance rate was relatively low (57%) and does not achieve the requirement of herd immunity (i.e., 70%), governments and healthcare authorities should try to elevate parents' knowledge and trust in the COVID-19 vaccine, facilitate in vaccination, and reduce their mental difficulties to improve the overall vaccination rate among children. [ABSTRACT FROM AUTHOR]

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Aeromonas veronii is a human and animal co-pathogenic bacterium that could have a significant negative impact on both human health and aquaculture. In this study, a mutant strain of A. veronii with deletion of the hemolysin co-regulated protein (hcp) gene was constructed (Δhcp-AV). Compared with the wild strain, Δhcp-AV showed significantly reduced growth capacity and biofilm formation ability. Motility tests showed that the hcp gene had no significant effect on the swimming and swarming ability. In addition, the pathogenicity was also reduced. To evaluate the efficacy of Δhcp-AV as a live attenuated vaccine for prevention of Aeromonas veronii infection, we compared the immune response of largemouth bass (Micropterus salmoides) after immunization with 500 μL of 1.47 × 10 5  CFU/mL of Δhcp-AV and 4 × 10 8  CFU/mL of inactivated A. veronii. Obvious increases of serum immune related enzyme activity were observed in immunization groups. Expression levels of immune-related genes in Δhcp-AV group were up-regulated, and higher than those in inactivated A. veronii group. After challenging with live A. veronii, the relative percent survival (RPS) was 100% in Δhcp- AV group, whereas the RPS was 76.67% in inactivated A. veronii group. Our data suggest that the live attenuated vaccine Δhcp- AV could elicit a stronger immune response and provide a higher RPS than inactivated A. veronii. These data suggest that hcp gene is an important virulence factor of A. veronii, and the live attenuated vaccine Δhcp-AV is safe and effective for prevention A. veronii infection in M. salmoides farming., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Listeria monocytogenes is the causative agent of listeriosis, which is dangerous for pregnant women, the elderly or individuals with a weakened immune system. Individuals with leukaemia, cancer, HIV/AIDS, kidney transplant and steroid therapy suffer from immunological damage are menaced. World Health Organization (WHO) reports that human listeriosis has a high mortality rate of 20-30% every year. To date, no vaccine is available to treat listeriosis. Thereby, it is high time to design novel vaccines against L. monocytogenes. Here, we present computational approaches to design an antigenic, stable and safe vaccine against the L. monocytogenes that could help to control the infections associated with the pathogen. Three vital pathogenic proteins of L. monocytogenes, such as Listeriolysin O (LLO), Phosphatidylinositol-specific phospholipase C (PI-PLC), and Actin polymerization protein (ActA), were selected using a subtractive proteomics approach to design the multi-epitope vaccine (MEV). A total of 5 Cytotoxic T-lymphocyte (CTL) and 9 Helper T-lymphocyte (HTL) epitopes were predicted from these selected proteins. To design the multi-epitope vaccine (MEV) from the selected proteins, CTL epitopes were joined with the AAY linker, and HTL epitopes were joined with the GPGPG linker. Additionally, a human β-defensin-3 (hBD-3) adjuvant was added to the N-terminal side of the final MEV construct to increase the immune response to the vaccine. The final MEV was predicted to be antigenic, non-allergen and non-toxic in nature. Physicochemical property analysis suggested that the MEV construct is stable and could be easily purified through the E. coli expression system. This in-silico study showed that MEV has a robust binding interaction with Toll-like receptor 2 (TLR2), a key player in the innate immune system. Current subtractive proteomics and immunoinformatics study provides a background for designing a suitable, safe and effective vaccine against pathogenic L. monocytogenes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Vaccination is the best way to prevent and reduce the damage caused by infectious diseases in animals and humans. So, several vaccines are used for prophylactic purposes before the pathogen infects, while therapeutic vaccines strengthen the immune system after infection with the pathogen. Adjuvants are molecules, compounds, or macromolecules that enhance non-specific immunity and, in collaboration with antigen(s), can improve the body's immune responses and change the type of immune response. The potential and toxicity of adjuvants must be balanced to provide the safest stimulation with the fewest side effects. In order to overcome the limitations of adjuvants and the effective and controlled delivery of antigens, attention has been drawn to nano-carriers that can be a promising platform for better presenting and stimulating the immune system. Some studies show that nanoparticles have a more remarkable ability to act as adjuvants than microparticles. Because nano-adjuvants inactively target antigen-presenting cells (APCs) and change their chemical surface, nanoparticles also perform better in targeted antigen delivery because they cross biological barriers more easily. We collected and reviewed various types of nano-adjuvants with their specific roles in immunogenicity as a prominent strategy used in veterinary vaccines in this paper. [ABSTRACT FROM AUTHOR]

It has been demonstrated that noncoding RNAs have significant physiological and pathological roles. Modulation of noncoding RNAs may offer therapeutic approaches as per recent findings. Small RNAs, mostly long noncoding RNAs, siRNA, and microRNAs make up noncoding RNAs. Inhibiting or promoting protein breakdown by binding to 3' untranslated regions of target mRNA, microRNAs post-transcriptionally control the pattern of gene expression. Contrarily, long non-coding RNAs perform a wider range of tasks, including serving as molecular scaffolding, decoys, and epigenetic regulators. This article provides instances of long noncoding RNAs and microRNAs that may be a biomarker of CVD (cardiovascular disease). In this paper we highlight various RNA-based vaccine formulation strategies designed to target these biomarkers—that are either currently in the research pipeline or are in the global pharmaceutical market—along with the physiological hurdles that need to be overcome. [ABSTRACT FROM AUTHOR]

Objective This paper highlights the occupational risk of Q fever from exposure to raw animal products in the context of multiple notified Q fever cases from 2020 to 2023 linked to four pet food manufacturing facilities in South-East Queensland, Australia. Methods The Queensland Government Notifiable Conditions System was used to identify Q fever cases linked to pet food manufacturing in the Metro North and Gold Coast Hospital and Health Service areas of Brisbane, Australia. Data on each case from routine public health follow-up were collected and descriptively analysed. Results Between 2020 and 2023, 12 confirmed Q fever infections (17% of total cases) were linked to four pet food manufacturing facilities. Eleven cases reported direct or environmental exposure to raw meat and animal products. None were previously vaccinated for Q fever. Conclusion These cases demonstrate the increased risk of Q fever infection as part of the pet food manufacturing process, highlighting an underappreciated preventable occupational risk, which can be mitigated with the use of pre-screening and vaccination of workers. All occupations should conduct workplace-based risk assessments to identify risks such as Q fever to prevent adverse negative health outcomes. [ABSTRACT FROM AUTHOR]

The antigens for acellular pertussis vaccines are made up of protein components that are purified directly from Bordetella pertussis (B. pertussis) bacterial fermentation. As such, there are additional B. pertussis toxins that must be monitored as residuals during process optimization. This paper describes a liquid chromatography mass spectrometry (LC-MS) method for simultaneous analysis of residual protein toxins adenylate cyclase toxin (ACT) and dermonecrotic toxin (DNT), as well as a small molecule glycopeptide, tracheal cytotoxin (TCT) in a Pertussis toxin vaccine antigen. A targeted LC-MS technique called multiple reaction monitoring (MRM) is used for quantitation of ACT and TCT, which have established limits in drug product formulations. However, DNT is currently monitored in an animal test, which does not have an established quantitative threshold. New approaches for DNT testing are discussed, including a novel standard based on concatenated quantitation sequences for ACT and DNT. Collectively, the method represents a "3-in-1" analytical simplification for monitoring process-related residuals during development of B. pertussis vaccines.

A low-cost fabrication method of microfluidic devices with micrometer-sized constrictions used for electrodeless dielectrophoresis (eDEP) is demonstrated here. A structure on a commercial printed circuit board (PCB) template of one-sided copper clad fiberglass-epoxy laminate was used as a molding master for polydimethylsiloxane (PDMS) soft lithography. This was achieved by printing a constriction-based microchannel pattern on glossy paper with a micrometer-scaled resolution laser printer and transferring it to the laminate's Cu face, rendering a microstructure of ∼17 µm height and various widths across tips. The Cu master's pattern was transferred to PDMS, and smooth constrictions were observed under the microscope. Following air plasma encapsulation, PDMS chips were loaded with an inactivated bacterial sample of fluorescently stained Brucella abortus vaccine strain S-19 and connected to an amplified voltage source to examine the sample's response to electric field variations. After an AC/DC electric field was applied to the bacterial solution in the microfluidic device, the combined effect of electrokinetic + hydrodynamic mechanisms that interact near the dielectric microconstrictions and exert forces to the sample was observed and later confirmed by COMSOL simulations. Our fabrication method is an alternative to be used when there is no access to advanced microfabrication facilities and opens ways for target selection and preconcentration of intracellular pathogens as well as sample preparation for metagenomics. [ABSTRACT FROM AUTHOR]

Plant-based virus-like particle (VLP) vaccines have been studied for years, demonstrating their potential as antigen-presenting platforms. In this paper, we describe the development of, and compare between, simple Escherichia coli-based antigen display platforms for the generation of potato virus Y (PVY) VLP-derived vaccines, thus allowing the production of vaccines from a single bacterial cell culture. We constructed four systems with the major cat allergen Fel d 1; namely, direct fusion with plant virus PVY coat protein (CP), mosaic PVY VLPs, and two coexpression variants of conjugates (SpyTag/SpyCatcher) allowing coexpression and conjugation directly in E. coli cells. For control experiments, we included PVY VLPs chemically coupled with Fel d 1. All constructed PVY–Fel d 1 variants were well expressed and soluble, formed PVY-like filamentous particles, and were recognized by monoclonal Fel d 1 antibodies. Our results indicate that all vaccine variants induced high titers of anti-Fel d 1 antibodies in murine models. Mice that were immunized with the chemically coupled Fel d 1 antigen exhibited the highest antibody titers and antibody–antigen interaction specificity, as detected by binding avidity and recognition of native Fel d 1. IgG1 subclass antibodies were found to be the dominant IgG class against PVY–Fel d 1. PVY CP-derived VLPs represent an efficient platform for the comparison of various antigen presentation systems to help evaluate different vaccine designs. [ABSTRACT FROM AUTHOR]

The Tol/Pal system (also written as "The Tol-Pal system") is a set of protein complexes produced by most Gram-negative bacteria. It comprises the inner membrane-associated and the outer membrane-anchored subunits composed of the TolA, TolQ, and TolR proteins and the TolB and Pal proteins, respectively. Although the Tol/Pal system was first defined as bacterial proteins involved in colicin uptake of Escherichia coli, its global roles have been characterized in several studies as mentioned in this article. Pathogenesis of many Gram-negative pathogens is sustained by the Tol/Pal system. It is also essential for cell growth and fitness in some pathogens. Therefore, the Tol/Pal system is proposed as a potential target for antimicrobial chemotherapy. Although the tol/pal mutants are low in virulence, they still have the ability to stimulate the immune system. The Pal protein is highly immunogenic and induces both adaptive and innate immune responses. Therefore, the tol/pal mutant strains and Pal proteins also have potential vaccine properties. For these reasons, the Tol/Pal system represents a promising research target in the development of antibacterial therapeutic strategies for refractory infections caused by multi-drug-resistant (MDR), Gram-negative pathogens. In this paper, we summarize studies on the Tol/Pal system associated with bacterial pathogenesis and vaccine development. [ABSTRACT FROM AUTHOR]

Although the therapeutic effect of mycobacteria as antitumor agents has been known for decades, recent epidemiological and experimental studies have revealed that mycobacterium-related chronic inflammation may be a possible mechanism of cancer pathogenesis. Mycobacterium tuberculosis and non-tuberculous Mycobacterium avium complex infections have been implicated as potentially contributing to the etiology of lung cancer, whereas Mycobacterium ulcerans has been correlated with skin carcinogenesis. The risk of tumor development with chronic mycobacterial infections is thought to be a result of many host effector mechanisms acting at different stages of oncogenesis. In this paper, we focus on the nature of the relationship between mycobacteria and cancer, describing the clinical significance of mycobacteria-based cancer therapy as well as epidemiological evidence on the contribution of chronic mycobacterial infections to the increased lung cancer risk.

Objective: Keeping in view, the constraints faced by the Indian broiler industry with lack of a suitable vaccine against Necrotic Enteritis (NE), a study has been proposed to explore the prevalence and detail characterization of C. perfringens type G in NE suspected broiler chicken in the process of suitable vaccine development., Methods: Intestinal scrapings/faecal contents of NE suspected broiler chickens were screened to establish the prevalence of C.perfringens type G in broiler birds. A most pathogenic, highly resistant type G isolate of C. perfringens, bearing both tpeL and gapC gene was selected for preparation of three different vaccine formulations, and to evaluate their immunogenic potential in broiler birds., Results: Screening of clinical samples of NE suspected broiler birds revealed C. perfringens type G, bearing gapC gene in 51.22% samples, of which 47.62% revealed tpeL gene. Seven of the tpeL pos type G isolates were comparatively more pathogenic for mice, of which, one exhibited multidrug resistance towards ciprofloxacin, norfloxacin, tetracycline and levofloxacin. The sonicated supernatant (SS) prepared from the selected tpeL and gapC positive isolate could maintain a significantly higher protective IgG response than toxoid and bacterin preparation from the 21st to 28 th day of age in immunized birds., Conclusion: The additional TpeL toxin in C. perfringens type G has been proved to be an additional key biological factor in the pathogenesis of NE in broiler chickens. Considering the release of more immunogenic proteins, the SS proved to be a better immunogenic preparation against NE with a multiple immunization dose., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Vaccination is one of the most effective public health interventions. We investigate the impact of vaccination activities for Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae , and yellow fever over the years 2000-2030 across 112 countries., Methods: Twenty-one mathematical models estimated disease burden using standardised demographic and immunisation data. Impact was attributed to the year of vaccination through vaccine-activity-stratified impact ratios., Results: We estimate 97 (95%CrI[80, 120]) million deaths would be averted due to vaccination activities over 2000-2030, with 50 (95%CrI[41, 62]) million deaths averted by activities between 2000 and 2019. For children under-5 born between 2000 and 2030, we estimate 52 (95%CrI[41, 69]) million more deaths would occur over their lifetimes without vaccination against these diseases., Conclusions: This study represents the largest assessment of vaccine impact before COVID-19-related disruptions and provides motivation for sustaining and improving global vaccination coverage in the future., Funding: VIMC is jointly funded by Gavi, the Vaccine Alliance, and the Bill and Melinda Gates Foundation (BMGF) (BMGF grant number: OPP1157270 / INV-009125). Funding from Gavi is channelled via VIMC to the Consortium's modelling groups (VIMC-funded institutions represented in this paper: Imperial College London, London School of Hygiene and Tropical Medicine, Oxford University Clinical Research Unit, Public Health England, Johns Hopkins University, The Pennsylvania State University, Center for Disease Analysis Foundation, Kaiser Permanente Washington, University of Cambridge, University of Notre Dame, Harvard University, Conservatoire National des Arts et Métiers, Emory University, National University of Singapore). Funding from BMGF was used for salaries of the Consortium secretariat (authors represented here: TBH, MJ, XL, SE-L, JT, KW, NMF, KAMG); and channelled via VIMC for travel and subsistence costs of all Consortium members (all authors). We also acknowledge funding from the UK Medical Research Council and Department for International Development, which supported aspects of VIMC's work (MRC grant number: MR/R015600/1).JHH acknowledges funding from National Science Foundation Graduate Research Fellowship; Richard and Peggy Notebaert Premier Fellowship from the University of Notre Dame. BAL acknowledges funding from NIH/NIGMS (grant number R01 GM124280) and NIH/NIAID (grant number R01 AI112970). The Lives Saved Tool (LiST) receives funding support from the Bill and Melinda Gates Foundation.This paper was compiled by all coauthors, including two coauthors from Gavi. Other funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication., Competing Interests: JT, SE, XL, KA, EC, HC, AC, Md, KE, MF, IG, TH, WH, DH, JH, KJ, AK, PK, AK, JL, XL, TM, CM, SM, SN, TP, AP, DR, SR, CS, SS, YT, HT, QT, ST, EV, NW, AW, KW, NF, KG No competing interests declared, MJ MLJ has received research funding from Sanofi Pasteur unrelated to the present work, MJ Reviewing editor, eLife, BL BAL reports grants and personal fees from Takeda Pharmaceuticals, personal fees from World Health Organization, outside the submitted work, TP TAP receives support from Emergent Biosolutions for work unrelated to his contribution to this study, HR HR is an employee of Center for Disease Analysis Foundation which has received grants from Gilead Sciences, AbbVie, Zeshan Foundation and EndHep2030 fund for projects unrelated to this work; HBV epidemiology data was funded by a grant from John Martin Foundation (Grant number 24), CT CLT received a consulting payment from GSK in 2018 (outside the submitted work), (© 2021, Toor et al.)

Mycoplasma hyopneumoniae (M. hyopneumoniae) is one of the primary agents involved in the porcine respiratory disease complex, economically one of the most important diseases in pigs worldwide. The pathogen adheres to the ciliated epithelium of the trachea, bronchi, and bronchioles, causes damage to the mucosal clearance system, modulates the immune system and renders the animal more susceptible to other respiratory infections. The pathogenesis is very complex and not yet fully understood. Cell-mediated and likely also mucosal humoral responses are considered important for protection, although infected animals are not able to rapidly clear the pathogen from the respiratory tract. Vaccination is frequently practiced worldwide to control M. hyopneumoniae infections and the associated performance losses, animal welfare issues, and treatment costs. Commercial vaccines are mostly bacterins that are administered intramuscularly. However, the commercial vaccines provide only partial protection, they do not prevent infection and have a limited effect on transmission. Therefore, there is a need for novel vaccines that confer a better protection. The present paper gives a short overview of the pathogenesis and immune responses following M. hyopneumoniae infection, outlines the major limitations of the commercial vaccines and reviews the different experimental M. hyopneumoniae vaccines that have been developed and tested in mice and pigs. Most experimental subunit, DNA and vector vaccines are based on the P97 adhesin or other factors that are important for pathogen survival and pathogenesis. Other studies focused on bacterins combined with novel adjuvants. Very few efforts have been directed towards the development of attenuated vaccines, although such vaccines may have great potential. As cell-mediated and likely also humoral mucosal responses are important for protection, new vaccines should aim to target these arms of the immune response. The selection of proper antigens, administration route and type of adjuvant and carrier molecule is essential for success. Also practical aspects, such as cost of the vaccine, ease of production, transport and administration, and possible combination with vaccines against other porcine pathogens, are important. Possible avenues for further research to develop better vaccines and to achieve a more sustainable control of M. hyopneumoniae infections are discussed.

Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines, as such a vaccine has been proven to be successful in the past. The expression of recombinant antigens in meningococcal Outer Membrane Vesicles (OMVs), with the OMV functioning both as adjuvant and delivery vehicle, greatly enhances their potential. Immunization studies in mice have shown that OMV-based vaccines can protect against various pathogens and an OMV-based meningococcal vaccine is approved and available for human use. Because of its surface localization in Borrelia and the detailed knowledge regarding its immunogenicity and structure, OspA was chosen as a suitable lipoprotein to be tested as an OMV-based vaccine against Lyme borreliosis. We have previously shown that the OMV-OspA vaccine was immunogenic in mice and here we assessed the efficacy of OMV-OspA. We generated a second-generation OMV-OspA vaccine and vaccinated C3H/HeN mice with (EDTA extracted) meningococcal OMVs expressing OspA from B. burgdorferi strain B31. The adjuvant effect of empty OMVs on recombinant OspA was tested as well. We subsequently challenged mice with a subcutaneous injection of B. burgdorferi. Average antibody end-point titers against the OspA-OMV construct were high, although lower compared to the antibodies raised against recombinant OspA. Interestingly, antibody titers between recombinant OspA adjuvanted with aluminum hydroxide and recombinant OspA with OMV as adjuvant were comparable. Finally, qPCR and culture data show that both the OspA-OMV and the vaccine based on recombinant OspA with OMV as adjuvant provided significant, yet partial protection, against Borrelia infection. OMV-based vaccines using Borrelia (lipo)proteins are an easy and feasible vaccination method protecting against B. burgdorferi infection and could be a promising strategy in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gram-negative bacteria produce outer membrane vesicles (OMVs) with 10 to 300 nm of diameter. The contribution of OMVs to bacterial pathogenesis is a topic of great interest, and their capacity to be combined with antigens impact in the future to the development of vaccines., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Noemi Furuyama and Marcelo Palma Sircili.)

Q fever is caused by the obligate intracellular bacterium, Coxiella burnetii , a designated potential agent of bioterrorism because of its route of transmission, resistance to disinfectants, and low infectious dose. The only vaccine licensed for human use is Q-VAX ® (Seqirus, licensed in Australia), a formalin-inactivated whole-cell vaccine, which produces severe local and systemic reactogenic responses in previously sensitized individuals. Accordingly, the U.S. Food and Drug Administration and other regulatory bodies around the world, have been reluctant to approve Q-VAX for widespread use. To obviate these adverse reactions, we prepared recombinant protein subunit vaccine candidates containing purified CBU1910, CBU0307, CBU0545, CBU0612, CBU0891, and CBU1398 proteins and TLR triagonist adjuvants. TLR triagonist adjuvants combine different TLR agonists to enhance immune responses to vaccine antigens. We tested both the protective efficacy and reactogenicity of our vaccine candidates in Hartley guinea pigs using intratracheal infection with live C. burnetii . While all of our candidates showed varying degrees of protection during challenge, local reactogenic responses were significantly reduced for one of our vaccine candidates when compared with a formalin-inactivated whole-cell vaccine. Our findings show that subunit vaccines combined with novel TLR triagonist adjuvants can generate protective immunity to C. burnetii infection while reducing reactogenic responses., Competing Interests: PF, DD, JF, LL, SJ, RN, and AJ own shares in Nanommune Inc. Nanommune does not sell the arrays described in this paper, nor funded any part of the work described herein. Neither Nanommune or its shareholders are likely to benefit from the results described in this publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fratzke, Jan, Felgner, Liang, Nakajima, Jasinskas, Manna, Nihesh, Maiti, Albin, Esser-Kahn, Davies, Samuel, Felgner and Gregory.)

Background: Asplenic or splenectomized patients have a higher risk (ranging from 10 to 50-fold) than the general population of developing an overwhelming post-splenectomy infection (OPSI). Thus, they should receive specific vaccinations to prevent bacterial infections and influenza. The aim of this meta-analysis was to estimate vaccination coverage (VC) with the recommended vaccines among splenectomized patients; strategies recommended in those studies to improve VC worldwide are considered as well., Research Design and Methods: Scopus, MEDLINE/PubMed, Google Scholar and ISI Web of Knowledge databases were searched. Research papers, short reports, reviews, and meta-analyses published between January 1, 2010 and July 18, 2020 were included; no geographic restrictions were included. Twenty-four studies were included in the meta-analysis., Results: For anti-pneumococcal vaccination, coverage was 55.1% (95%CI = 41.0-69.2%), for anti-Hib 48.3% (95%CI = 34.3-52.3%), for anti-meningococcal C/ACYW135 33.7% (95%CI = 23.6-43.9%), for anti-meningococcal B 13.3% (95%CI = 7.0-19.5%) and for anti-influenza 53.2% (95%CI = 22.0-84.4%). Most studies determined a lack of adherence to international guidelines by healthcare workers and suggested the need to better educate health professionals in the management of post-splenectomy patients., Conclusions: The meta-analysis showed the suboptimal immunization coverage for the vaccines recommended for asplenic patients. Greater efforts must be made by public health professionals to increase VC in this group of patients at risk. Introducing specific prophylaxis protocols in the clinical routine seems to guarantee better immunization compliance in those patients.

Immersion vaccination relies on the response of fish mucosa-associated lymphoid tissues, the Crucian carp ( Carassius auratus ) and Grouper ( Epinephelus coioides ) were researched in this paper to examine local mucosal immune responses and associated humoral system responses following immersion vaccination. We administered 1.5 × 10 7 CFU/ml formalin-inactivated Vibrio harveyi cells and measured mucus and serum antibody titers as well as IgM, MHC II mRNA levels in immune organs. The mucosal antibody response preceded the serum response indicating a role for local mucosal immunity in immersion vaccination. IgM and MHC II mRNA levels were relatively greater for the spleen and head kidney indicating the importance and central position of systemic immunity. Expression levels were also high for the gills while skin levels were the lowest. IgM and MHC II mRNA levels were altered over time following vaccination and the hindgut, liver and spleen were similar indicating a close relationship, so the absolute value of r is used to analyze the correlation among different organs immunized. It can be inferred the existence of an internal immune molecular mechanism for Immune synergy hindgut-liver-spleen, from the peak time (14 th day), the relative ratio of genes expression in the same tissues between the immunized grouper and the control group (26 times), and Pearson correlation coefficient (0.8<| r |<1). Injection challenges with live V. harveyi indicated that the relative protection rates for the crucian carp and Grouper was basically the same at 44.4% and 47.4%, respectively. It is believe that crucian carp may be used as a substitute for the valuable grouper in immunity experiment, just from aspect of the relative percent survival (RPS) and how it changes with time. But they were not consistent about the IgM mRNA expression between that of crucian carp and grouper after immersion the Vibrio vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gong, Wang, Lai, Zhao, Sun, Chen, Tao and Huang.)

Background: This first in human study was designed as an open label clinical trial to assess the safety and tolerability of Serum Institute of India Pvt. Ltd. (SIIPL) Tdap vaccine in healthy adult volunteers, aged 18-45 years., Methods: A total of 24 healthy adults were administered a 0.5 ml single dose of SIIPL Tdap vaccine intramuscularly, and were followed for one month for safety outcomes viz., immediate, solicited, unsolicited and serious adverse events., Results: 23 subjects completed the study in compliance with the study protocol. None of the participants experienced any immediate adverse events or any local or systemic solicited adverse events., Conclusion: Tdap vaccine manufactured by Serum Institute of India Pvt. Ltd. is safe and well tolerable in adults. It was concluded that further clinical development of this vaccine should continue to assess its safety and immunogenicity, in the target population. Clinical Trial Registration - CTRI/2017/03/008003., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Contacts of leprosy patients have an increased risk of infection with Mycobacterium leprae. Contact tracing and chemo- or immunoprophylaxis are important means of preventing leprosy transmission., Aims: We aimed to evaluate the efficacy of immunoprophylaxis with Mycobacterium indicus pranii vaccine in reducing anti-phenolic glycolipid-1 titers in household contacts of leprosy patients., Methods: This prospective single-center study was conducted in a tertiary care center in North India from January 2015 to December 2016. Contacts of leprosy patients (both paucibacillary and multibacillary) were screened for anti-phenolic glycolipid-1 antibodies with enzyme-linked immunosorbent assay. Those found positive were given immunoprophylaxis with a single dose of Mycobacterium indicus pranii vaccine, and anti-phenolic glycolipid-1 titers were evaluated at six and 12 months. All contacts were clinically followed for three years., Results: Of the 135 contacts of 98 leprosy patients that were screened, 128 were recruited. Seventeen of these contacts were positive for anti-phenolic glycolipid-1 antibodies and were given Mycobacterium indicus pranii vaccine. Two contacts were lost to follow-up. After immunoprophylaxis, anti-phenolic glycolipid-1 titers were negative in all patients at all intervals, and no contact developed any clinical signs or symptoms of leprosy during the three-year follow-up., Limitations: The small number of contacts studied, the short follow-up period and the absence of a control group were limitations of this study. Dicussion: We could not find any papers on natural decline of PGL 1 titres in contacts, although in leprosy patients, these titres may even increase after completion of treatment. However the titres do correlate with bacterial load (reference: Int J Lepr Other Mycobact Dis. 1998 Sep;66(3):356-64) so if the tires decrease or become negative it may be considered as an indirect evidence of bacillary clearance. Hence we may suggest the protective efficacy. Furthermore, as the editor mentioned, considering the small number of positive patients, a control group was not possible in the present pilot study, but such studies may be carried out in the future., Conclusion: Immunoprophylaxis with Mycobacterium indicus pranii vaccine is effective and safe in preventing disease in contacts of leprosy patients. However, these findings need to be replicated in larger studies.

Clostridioides difficile ( C. difficile , previously known as Clostridium difficile ) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES : Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.

Today, Coronavirus Disease 2019 (COVID-19) is a global public health emergency and vaccination measures to counter its diffusion are deemed necessary. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of the disease, unleashes a T-helper 2 immune response in those patients requiring intensive care. Here, we illustrate the immunological mechanism to train the immune system towards a more effective and less symptomatic T-helper 1 immune response, to be exploited against SARS-CoV-2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Query fever is a zoonotic disease caused by Coxiella burnetii. There is no universal method for the prevention of this disease. Recombinant vaccine is a potent strategy that can be utilized for this purpose. The current study was conducted to develop a multi-epitope vaccine against Coxiella burnetii. Hence, OmpA, Tuf2, GroEL, Mip and sucB antigens were used for the prediction of epitopes. Then, a multi-epitope vaccine was developed based on a molecular adjuvant and fragments that contained the best MHCI, B cell, MHCII and IFN-γ epitopes. The features of the developed vaccine including physicochemical parameters, antigenicity and protein structures were assessed. Also, interaction between the developed vaccine and TLR4/MD2 receptor along with molecular dynamics of the ligand-receptor complex were investigated. Finally, the codon adaptation and cloning were conducted for the developed vaccine. According to the results, molecular weight, instability index, antigenicity and random coil percentage of the developed vaccine were 54.4 kDa, 32.84, 1.1936 and 34.92%, respectively. Besides, residues distribution in core region of the refined model was 85%. The results demonstrated that the developed vaccine could dock to its receptor with the lowest energy of -976.7 as well as RMSD value of the complex was between 0.15 and 0.22 nm. Also, the results showed that CIA index of the codon adapted sequence was 0.95. Finally, cloning results revealed that nucleotide sequence of the developed vaccine could be successfully cloned into pET-21a (+). Based on these results, it seems that the developed vaccine can be a suitable candidate to prevent Coxiella burnetii., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

The aims of this research were to determine the uptake of a national strategy to reduce lameness in the UK flock, known as the Five-Point Plan (5 P P); explore the association between footrot vaccination (Footvax®) use and 5 P P adoption; investigate the management practices associated with farmer-reported percentage lameness through risk factor analysis; and identify the population attributable fractions of these management practices. In 2014, the 5 P P was launched to provide a practical, farm-level framework to help farmers reduce lameness to reach Farm Animal Welfare Committee (FAWC) targets. No published studies have explicitly explored its uptake in UK flocks nor its association with lameness prevalence. Understanding what parts of the 5 P P farmers adopt and which elements contribute towards the greatest reduction in lameness are integral in informing future strategies. Between November 2018 and February 2019, 532 UK sheep farmers completed a cross-sectional online and paper-based survey. The geometric mean of farmer-reported percentage lameness in ewes was 3.2 % (95 % CI: 2.8-3.6). Farmers adopted a median of 3 points of the plan, but was only fully-adopted by 5.8 % of farmers. The number of points adopted increased with flock size, with larger commercial flocks more likely to cull and vaccinate against footrot, but smaller, pedigree flocks were more likely to treat individual lame sheep. Vaccination was poorly associated with the uptake of other points of the 5 P P. Eight flock management factors were associated with significantly higher percentage lameness in ewes; not carrying out measures to avoid lameness transmission, not quarantining bought in stock, not treating individual lame sheep within three days, maintaining an open flock and foot trimming were all associated with a higher risk of lameness in flocks studied. In addition, using Footvax® for ≤5 years was associated with a higher risk of lameness, although vaccination could be a consequence of high flock lameness or these farmers were not implementing other effective managements, such as treating promptly. The highest PAFs were calculated for trimming lame sheep (16.9 %), maintaining an open flock (13.5 %) and not carrying out measures to avoid lameness transmission (11.8 %). We provide new evidence documenting the benefits of adopting parts of the 5 P P on reducing lameness prevalence in UK flocks, although uptake of these measures could be improved in flocks. Encouraging uptake of these measures could make an important contribution towards reducing the prevalence of lameness and reaching 2021 FAWC ≤ 2% lameness prevalence targets., Competing Interests: Declaration of Competing Interest Caroline Best is part-funded by MSD Animal Health., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Leptospira interrogans, Borrelia burgdorferi, and Treponema pallidum are important pathogenic spirochetes. The incidence of human diseases caused by pathogenic spirochetes, e.g., leptospirosis, Lyme disease, and syphilis, has been recently increased, posing a threat to public health. Mechanisms of spirochete pathogenicity are not yet fully understood, and no safe and effective vaccine to prevent and control the infection by pathogenic spirochetes is currently available. In this article, we review the progress of research into the pathogenic spirochete vaccine, mainly in terms of vaccine types. The development of relevant vaccines against pathogenic spirochetes has generally proceeded via several stages, such as the whole-cell inactivated vaccine, live attenuated vaccine, and gene-engineered vaccine, and will likely enter a new stage with the application of gene editing technology. In this review, we mainly summarized the types of pathogenic spirochete vaccines and conducted a preliminary analysis on the protective effect of immunity, and proposed a further prospect for the development of pathogenic spirochete vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bovine anaplasmosis is a globally economically important tick-borne disease caused by the obligate intraerythrocytic rickettsia, Anaplasma marginale. A live Anaplasma centrale blood-based vaccine is available, but it does not protect against all A. marginale field strains and may also transmit other blood-borne pathogens. Five potential outer membrane protein (OMP) vaccine candidates have been well-characterised in A. marginale strains from the USA, however, their levels of conservation in other countries must be ascertained in order to inform their use in a vaccine with regional or global efficacy. This study assessed the amino acid variation in vaccine candidate OMPs in South African strains of A. marginale, and also compared the immunogenic properties between South African and US strains. OMP genes Am779, Am854, omp7, omp8 and omp9 were amplified and sequenced from a set of genetically diverse South African samples with different msp1α-genotypes. OMPs Am854 and Am779 were highly conserved, with 99-100 % amino acid identity, while Omp7, Omp8 and Omp9 had 79-100 % identity with US strains. As has been shown previously, Omp7-9 possess conserved N- and C- termini, a central variable region, and a highly conserved CD4 T-cell epitope, FLLVDDA(I/V)V, in the N-terminal region. Western blot analysis of recombinant OMPs indicates strong antigenic conservation between South African and US strains of A. marginale, suggesting that they are good candidates for use in a novel global vaccine cocktail, although further work on the best formulation and delivery methods will be necessary., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Edwardsiellosis outbreaks cause significant losses in Japanese eel aquaculture. The causative agent, Edwardsiella tarda, is an intracellular pathogen, and the use of antibiotics has a limited effectiveness. As Japanese eels are sensitive to stress, injection vaccines are not recommended for treatment; immersion methods are less stressful, but not cost-effective. Alternatively, oral vaccination methods are more promising. The aim of this study was to develop a starch hydrogel-based oral (SHO) vaccine against edwardsiellosis in Japanese eel, using formalin-killed cells. To assess the protective effect, we compared SHO vaccine with the conventional formalin-killed cell (FKC) vaccine. A bacterial agglutination test showed that agglutination titers in SHO-vaccinated group were higher than in the FKC-vaccinated group. Japanese eel survival rate (%) was monitored after challenge by E. tarda at four weeks post-vaccination. Survival rates in the FKC group (60%, first trial; 70%, second trial) were lower than in SHO groups. Percentage survival rates in three SHO groups (first and second trials, respectively) were as follows: 70% and 80% in the group vaccinated once per day for one day; and 80% and 90% in both groups vaccinated for four and eight days. Additionally, a boost SHO vaccination at 46 days prompted a similar or even higher protection against edwardsiellosis than after the initial vaccination. Both FKC and SHO vaccination upregulated levels of pro-inflammatory cytokines (interleukin (IL)-6, tumor necrosis factor (TNF)-α), and host defense cytokine (interferon (IFN)-α) in all immunized groups of fish when compared with the control. These results reveal the immunostimulation effect of SHO vaccine in Japanese eel, emphasizing its potential as an oral vaccine in aquaculture., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Botulinum neurotoxins (BoNTs) are highly toxic proteins that mediate their effects by binding to neuronal receptors and block the neutralizing ability of therapeutic antibodies. Vaccination is currently the most effective strategy to prevent botulism. In this study, a series of recombinant functional domain antigens of BoNT/A were prepared and identified, and their immunoprotective efficacies were explored and compared. Our results showed that all antigens produced strong humoral immune responses, although their protective effects against the toxin were different. Only the Hc and HN-L antigens produced strong protective effects and afforded complete immunoprotection. In addition, the combined vaccine groups showed that there was no synergistic effect on immune responses after antigen combination, suggesting that the integrity of the toxin antigen or domain is crucial to the immune effects. Studies of the dose-dependent immunoprotective effects further confirmed that the Hc domain antigen afforded more effective protective potency than the HN-L antigen, equivalent to the immune effect of the full-length toxin (Hc + HN-L combination group). Overall, our results demonstrated that the Hc domain elicited a strong protective immune response and also provided basic data and theoretical support for the development of Hc-based BoNT/A subunit vaccine. Therefore, the receptor binding domain Hc is implicated as a promising target antigen of the BoNT/A recombinant subunit vaccine as an alternative to the toxoid vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Helicobacter pylori is a human class I carcinogen and no effective prophylactic or therapeutic H. pylori vaccine has yet been marketed. H. pylori can escape the host immune response, but the precise immune protection mechanisms in humans remain unknown. In this study, we developed a multivalent, subunit H. pylori vaccine candidate by formulating three commonly used H. pylori antigens, neutrophil-activating protein (NAP), urease subunit A (UreA) and subunit B (UreB) with the mucosal adjuvant, a double-mutant heat-labile toxin (dmLT) from Escherichia coli, and evaluated its immunogenicity and therapeutic efficacy in a mouse model of H. pylori infection. We found that oral immunization of H. pylori-infected mice significantly reduced gastric bacterial colonization at both 2 and 8 weeks after immunization. The reduction in bacterial burdens was accompanied with significantly increased serum antigen-specific IgG responses and mucosal IgA responses. Moreover, oral immunization also induced Th1/Th17 immune responses, which may play a synergistic role with the specific antibodies in the elimination of H. pylori. Thus, our vaccine candidate appears able to overcome the immune evasion mechanism of H. pylori, restore the suppression of Th2 immune responses with the induction of a strong humoral immune response. These results lay the foundation for the development of an optimized oral therapeutic H. pylori vaccine with increased immunogenicity of UreA and UreB, as well as providing long-term immunity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Toxoid vaccines against Clostridium difficile infections (CDI) appear promising in reducing the risk of developing toxin-mediated symptoms. We sought to evaluate the effectiveness and cost-effectiveness of a vaccine candidate in a hospital setting. We developed an agent-based simulation model of nosocomial CDI in a 300-bed hospital. Targeting high-risk patients for vaccination, we estimated the reduction of symptomatic CDI. Using the net reduction of CDI-associated isolation days, we evaluated the vaccine's cost-effectiveness from a healthcare provider perspective over a 2-year period with an average monthly incidence of 5 cases per 10,000 patient-days pre-vaccination. Assuming a vaccine efficacy in the range 60-90%, vaccinating 40% of high-risk patients pre-admission reduced symptomatic CDI by 16.6% (95% CI: 15.2, 17.9). When the vaccine coverage increased to 80%, the reduction of symptomatic CDI was 34.6% (95% CI: 33.7, 35.9). For a willingness to pay (WTP) of CDN$1000 (corresponding to the average costs of case isolation per day), vaccine was cost-effective for vaccination costs per individual (VCPI) up to CDN$111 in the scenario of 40% vaccine coverage. With the same WTP, vaccine was cost-effective for VCPI up to CDN$121 when the vaccine coverage increased to 80%. A significant portion (~80%) of hospital colonization is caused by environmental transmission of C. difficile, which markedly reduced the effectiveness of vaccine below its assumed efficacy. However, due to the number of CDI-associated isolation days averted, vaccination of high-risk patients can be cost-effective depending on the WTP and the VCPI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)