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Melioidosis, caused by the intracellular bacterial pathogen and Tier 1 select agent Burkholderia pseudomallei (Bp), is a highly fatal disease endemic in tropical areas. No licensed vaccine against melioidosis exists. In preclinical vaccine studies, demonstrating protection against respiratory infection in the highly sensitive BALB/c mouse has been especially challenging. To address this challenge, we have used a safe yet potent live attenuated platform vector, LVS ΔcapB, previously used successfully to develop vaccines against the Tier 1 select agents of tularemia, anthrax, and plague, to develop a melioidosis vaccine. We have engineered melioidosis vaccines (rLVS ΔcapB/Bp) expressing multiple immunoprotective Bp antigens among type VI secretion system proteins Hcp1, Hcp2, and Hcp6, and membrane protein LolC. Administered intradermally, rLVS ΔcapB/Bp vaccines strongly protect highly sensitive BALB/c mice against lethal respiratory Bp challenge, but protection is overwhelmed at very high challenge doses. In contrast, administered intranasally, rLVS ΔcapB/Bp vaccines remain strongly protective against even very high challenge doses. Under some conditions, the LVS ΔcapB vector itself provides significant protection against Bp challenge, and consistent with this, both the vector and vaccines induce humoral immune responses to Bp antigens. Three-antigen vaccines expressing Hcp6-Hcp1-Hcp2 or Hcp6-Hcp1-LolC are among the most potent and provide long-term protection and protection even with a single intranasal immunization. Protection via the intranasal route was either comparable to or statistically significantly better than the single-deletional Bp mutant Bp82, which served as a positive control. Thus, rLVS ΔcapB/Bp vaccines are exceptionally promising safe and potent melioidosis vaccines.ImportanceMelioidosis, a major neglected disease caused by the intracellular bacterial pathogen Burkholderia pseudomallei, is endemic in many tropical areas of the world and causes an estimated 165,000 cases and 89,000 deaths in humans annually. Moreover, B. pseudomallei is categorized as a Tier 1 select agent of bioterrorism, largely because inhalation of low doses can cause rapidly fatal pneumonia. No licensed vaccine is available to prevent melioidosis. Here, we describe a safe and potent melioidosis vaccine that protects against lethal respiratory challenge with B. pseudomallei in a highly sensitive small animal model-even a single immunization is highly protective, and the vaccine gives long-term protection. The vaccine utilizes a highly attenuated replicating intracellular bacterium as a vector to express multiple key proteins of B. pseudomallei; this vector platform has previously been used successfully to develop potent vaccines against other Tier 1 select agent diseases including tularemia, anthrax, and plague.

Introduction: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). Methods: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. Results: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. Conclusions: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) are a significant global health issue, especially among women, with growing concerns related to antibiotic resistance and adverse effects. The Uromune®, a sublingual, heat-inactivated, polybacterial vaccine, represents a promising therapeutic alternative by enhancing immune responses against uropathogens. Methods: This pilot retrospective study, conducted at Hospital Universitari de Sant Joan de Reus from January 2018 to August 2022, assessed the association between Uromune® administration and changes in recurrent UTIs. Patients received personalized autovaccines administered as two sublingual puffs daily for three months. Clinical, microbiological, and demographic data were analyzed to assess treatment outcomes and identify recurrence-associated factors. Results: Forty-nine patients (mean age, 61 years, and 59.2% women) were included in the study. Uromune® treatment decreased UTI episodes from 3.73 ± 0.97 the year before to 0.98 ± 1.36 (p < 0.001) the year after its administration. The number of patients who suffered three or more episodes per year dropped from 43 (87.7%) before the intervention to 7 (14.3%) afterwards. The maximum effectiveness of the autovaccine was observed three months post-administration, with 44 patients not experiencing any UTI episodes. Regression analysis identified having had a urostomy, chronic kidney disease, and being immunosuppressed as predictors of recurrence. Conclusion: Uromune® autovaccine was associated with a significant reduction in the frequency of recurrent UTIs and related hospitalizations, offering substantial relief to patients. These findings suggest that Uromune® may be a promising option for managing recurrent UTIs, though controlled studies are needed to confirm its efficacy compared to standard treatments. [ABSTRACT FROM AUTHOR]

Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies. Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to rNa-GST-1. Following two immunizations, mRNA vaccines induced similar or superior levels of antigen-specific antibodies compared to rNa-GST-1. Secretory Na-GST-1 was comparable to rNa-GST1 in producing neutralizing antibodies against Na-GST-1's thiol transferase activity, while native Na-GST-1 induced a more robust CD8+ T cell response due to its intracellular accumulation. Although PM Na-GST-1 elicited one of highest titers of antigen-specific antibody and a diverse set of memory T-cell populations, it resulted in a lower ratio of neutralizing antibodies after IgG purification compared to the other vaccine candidates. Conclusions/significance: These findings emphasize the importance of antigen localization in tailoring immune responses and suggest that extracellular antigens are more effective for inducing humoral responses, whereas cytosolic antigen accumulation enhances MHC-1 peptide presentation. Future studies will determine if these in vitro and immunogenicity findings translate to in vivo efficacy. Altogether, mRNA vaccines offer numerous possibilities in the development of multivalent vaccines with single or multiple antigens. Author summary: Our work on Na-GST-1 mRNA vaccines addresses a critical need in the fight against hookworm infections, which affect more than 100 million people worldwide. Na-GST-1, a protein essential for the survival of hookworms, has been explored as a target for vaccine development. By using mRNA technology, we designed vaccine candidates that express and deliver Na-GST-1 to different locations in cells and tissues of immunized mice, including forms that are secreted, anchored to the plasma membrane, or retained within cells (the native form). Our findings reveal that the location of antigens within cells significantly impacts the immune response. Secreted and membrane-anchored forms of Na-GST-1 generated strong antibody responses, which are important for neutralizing Na-GST-1 in the hookworm. Meanwhile, the intracellular and membrane anchored forms elicited a robust cytotoxic cell response, which would be more important for targeting intracellular pathogens. This research not only advances our understanding of how protein localization affects immune responses but also highlights the versatility and potential of mRNA vaccines to target various pathogens by manipulating how and where vaccine antigens are presented to the immune system. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is a major global health issue and is recognized as the leading cause of cervical cancer. While prophylactic vaccination programs have led to substantial reductions in both HPV infection rates and cervical cancer incidence, considerable burdens of HPV-related diseases persist, particularly in developing countries with inadequate vaccine coverage and uptake. The development of therapeutic vaccines for HPV represents an emerging strategy that has the potential to bolster the fight against cervical cancer. Unlike current prophylactic vaccines designed to prevent new infections, therapeutic vaccines aim to eradicate or treat existing HPV infections, as well as HPV-associated precancers and cancers. This review focuses on clinical studies involving therapeutic HPV vaccines for cervical cancer, specifically in three key areas: the treatment of cervical intraepithelial neoplasia; the treatment of cervical cancer in combination with or without chemotherapy, radiotherapy, or immune checkpoint inhibitors; and the role of prophylaxis following completion of treatment. Currently, there are no approved therapeutic HPV vaccines worldwide; however, active progress is being made in clinical research and development using multiple platforms such as peptides, proteins, DNA, RNA, bacterial vectors, viral vectors, and cell-based, each offering relative advantages and limitations for delivering HPV antigens and generating targeted immune responses. We outline preferred vaccine parameters, including indications, target populations, safety considerations, efficacy considerations, and immunization strategies. Lastly, we emphasize that therapeutic vaccines for HPV that are currently under development could be an important new tool in fighting against cervical cancer. [ABSTRACT FROM AUTHOR]

Recoding strategies have emerged as a promising approach for developing safer and more effective vaccines by altering the genetic structure of microorganisms, such as viruses, without changing their proteins. This method enhances vaccine safety and efficacy while minimizing the risk of reversion to virulence. Recoding enhances the frequency of CpG dinucleotides, which in turn activates immune responses and ensures a strong attenuation of the pathogens. Recent advancements highlight synonymous recoding's potential, offering improved genetic stability and immunogenicity compared to traditional methods. Live vaccines attenuated using classical methods pose a risk of reversion to virulence and can be time-consuming to produce. Synonymous recoding, involving numerous codon alterations, boosts safety and vaccine stability. One challenge is balancing attenuation with yield; however, innovations like Zinc-finger antiviral protein (ZAP) knockout cell lines can enhance vaccine production. Beyond viral vaccines, recoding can apply to bacterial vaccines, as exemplified by modified Escherichia coli and Streptococcus pneumoniae strains, which show reduced virulence. Despite promising results, challenges like ensuring genetic stability, high yield, and regulatory approval remain. Briefly, ongoing research aims to harness these innovations for comprehensive improvements in vaccine design and deployment. In this commentary, we sought to further engage the community's interest in this elegant approach by briefly highlighting its main advantages, disadvantages, and future prospects. [ABSTRACT FROM AUTHOR]

Background: In the past decade, immunotherapy has become a major choice for the treatment of lung cancer, yet its therapeutic efficacy is still relatively limited due to the various immune escape mechanisms of tumors. Based on this, we introduce Neo-BCV, a novel bacterial composite vaccine designed to enhance immune responses against lung cancer. Methods: We investigated the immune enhancing effect of Neo-BCV through in vivo and in vitro experiments, including flow cytometry, RNA-seq, and Western blot. Results: We have demonstrated that Neo-BCV can promote Dendritic cells (DCs) maturation and induce DCs differentiation into pro-inflammatory subgroups, significantly enhancing cytotoxic T lymphocyte (CTL)-mediated anti-tumor responses. Transcriptome sequencing revealed that Neo-BCV exerts its effects by specifically inhibiting the JAK2-STAT3 signaling pathway, a crucial regulator of cancer progression, metabolism, and inflammation. Moreover, Neo-BCV significantly improved the immune microenvironment in both tumor and spleen tissues without inducing notable toxic effects in major organs. Conclusions: These findings highlight Neo-BCV's potential as a safe and effective therapeutic strategy, offering a novel avenue for clinical translation in lung cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Background/Objectives Bacterial ghosts (BGs), non-living empty envelopes of bacteria, are produced either through genetic engineering or chemical treatment of bacteria, retaining the shape of their parent cells. BGs are considered vaccine candidates, promising delivery systems, and vaccine adjuvants. The practical use of BGs in vaccine development for humans is limited because of concerns about the preservation of viable bacteria in BGs. Methods: To increase the efficiency of Klebsiella pneumoniae BG formation and, accordingly, to ensure maximum killing of bacteria, we exploited previously designed plasmids with the lysis gene E from bacteriophage φX174 or with holin–endolysin systems of λ or L-413C phages. Previously, this kit made it possible to generate bacterial cells of Yersinia pestis with varying degrees of hydrolysis and variable protective activity. Results: In the current study, we showed that co-expression of the holin and endolysin genes from the L-413C phage elicited more rapid and efficient K. pneumoniae lysis than lysis mediated by only single gene E or the low functioning holin–endolysin system of λ phage. The introduction of alternative lysing factors into K. pneumoniae cells instead of the E protein leads to the loss of the murein skeleton. The resulting frameless cell envelops are more reminiscent of bacterial sacs or bacterial skins than BGs. Although such structures are less naive than classical bacterial ghosts, they provide effective protection against infection by a hypervirulent strain of K. pneumoniae and can be recommended as candidate vaccines. For our vaccine candidate generated using the O1:K2 hypervirulent K. pneumoniae strain, both safety and immunogenicity aspects were evaluated. Humoral and cellular immune responses were significantly increased in mice that were intraperitoneally immunized compared with subcutaneously vaccinated animals (p < 0.05). Conclusions: Therefore, this study presents novel perspectives for future research on K. pneumoniae ghost vaccines. [ABSTRACT FROM AUTHOR]

Background: Vaccines development in this millennium started by the milestone work on Neisseriameningitidis B, reporting the invention of Reverse Vaccinology (RV), which allows to identify vaccine candidates (VCs) by screening bacterial pathogens genome or proteome through computational analyses. When NERVE (New Enhanced RV Environment), the first RV software integrating tools to perform the selection of VCs, was released, it prompted further development in the field. However, the problem-solving potential of most, if not all, RV programs is still largely unexploited by experimental vaccinologists that impaired by somehow difficult interfaces, requiring bioinformatic skills. Results: We report here on the development and release of NERVE 2.0 (available at: https://nerve-bio.org) which keeps the original integrative and modular approach of NERVE, while showing higher predictive performance than its previous version and other web-RV programs (Vaxign and Vaxijen). We renewed some of its modules and added innovative ones, such as Loop-Razor, to recover fragments of promising vaccine candidates or Epitope Prediction for the epitope prediction binding affinities and population coverage. Along with two newly built AI (Artificial Intelligence)-based models: ESPAAN and Virulent. To improve user-friendliness, NERVE was shifted to a tutored, web-based interface, with a noSQL-database to consent the user to submit, obtain and retrieve analysis results at any moment. Conclusions: With its redesigned and updated environment, NERVE 2.0 allows customisable and refinable bacterial protein vaccine analyses to all different kinds of users. [ABSTRACT FROM AUTHOR]

The efficacy of two Mycoplasma gallisepticum commercially available vaccines administered singly or in combination was evaluated in two trials; in both trials, specific-pathogen-free (SPF) chickens were vaccinated with the live attenuated F-strain vaccine at 5 weeks of age (WOA), an inactivated M. gallisepticum bacterin at 9 and 13 WOA, or both vaccines. In the first trial, groups of vaccinated birds, along with controls, were challenged via aerosol with virulent R-strain at 22 and 41 weeks of age. All of the vaccine programs evaluated showed a statistically significant reduction in colonization with the challenge strain following challenge at either timepoint. However, only the programs including the live vaccine also showed significant protection from respiratory lesions and ovarian regression; and although there were numerical differences indicating benefits of a combined (live + bacterin) program, the addition of bacterins did not enhance (or reduce) the efficacy of the F-strain vaccine in a statistically significant manner (P ≤ 0.05). In the second trial, groups of vaccinated birds, along with controls, were challenged via aerosol with different doses of virulent M. gallisepticum R-strain at 17 weeks of age. Both vaccination programs in this trial (live only and live + bacterin) resulted in significant protection against challenge strain colonization and air sac lesions (P ≤ 0.05); In addition, the live + bacterin program showed significantly improved results with respect to colonization with the challenge strain as well as protection from air sac lesions compared to the live vaccine alone (P ≤ 0.05). [ABSTRACT FROM AUTHOR]

Background Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention. Methods This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed. Results The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], −38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE = 28.6% (96.4% CI, −28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P =.02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups. Conclusions Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. Clinical Trials Registration NCT03090191. [ABSTRACT FROM AUTHOR]

Fasciola hepatica is a trematode parasite of significant veterinary and public health importance, causing economic losses in livestock due to liver damage, weight loss and reduced milk production. Although triclabendazole (TCZ) is available for treatment, it does not prevent the disease or reinfection. Infected animals exhibit strong immunoregulation, increasing susceptibility to secondary infections and altering vaccine‐induced antibody responses. This study investigates the humoral immune response in cattle infected with F. hepatica at different stages of infection and evaluates the effect of TCZ treatment on this response. It also examines how fasciolosis affects the antibody response induced by bacterial vaccines during early and chronic infection stages. Experimental infections in steers were conducted, with faecal and plasma samples collected at various intervals. The results showed a decrease in parasite‐specific antibody avidity during infection. However, F. hepatica infection did not substantially modify antibody response to bacterial vaccines. This study underscores the need for further research on the impact of fasciolosis and its treatment on livestock vaccination efficacy. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Given the potential consequences associated with urinary tract infections (UTIs), it has become standard practice to use continuous antibiotic prophylaxis (CAP) in children, even if controversial. We reviewed the effectiveness of CAP on recurrent UTI in a pediatric population to determine if equipoise remains and allows for a placebo control group to study the effectiveness of the vaccine MV140. METHODS: We completed a rapid review. We searched Medline, Embase and the Cochrane Library and data extraction was completed by a single reviewer. Our search criteria were 2005–2022, English and French language, randomized controlled trials (RCTs) and systematic reviews only. The population was 19 years and younger, including: vesicoureteral reflux (VUR), congenital anomalies of the kidneys and urinary tracts (CAKUT), and bladder and bowel dysfunction (BBD). RESULTS: Three RCTs and three systematic reviews found a benefit for CAP, mostly for a population with VUR, and those with severe VUR have more benefit. Most studies were not able to show a difference in the rate of UTIs or new renal scars (NRS). Three RCTs found a deleterious effect with CAP. Other studies were able to prove a benefit for patients with dilatation of the urinary tract without obstruction and high-grade VUR combined with BBD. The major adverse event found was antimicrobial resistance. CONCLUSIONS: High-risk patients benefit from CAP. The potential consequences of UTIs makes it unethical to use a placebo-only control group for them; however, CAP use seems difficult to justify in a low-risk population. [ABSTRACT FROM AUTHOR]

Bacterial infections have accompanied humanity for centuries. The discovery of the first antibiotics and the subsequent golden era of their discovery temporarily shifted the balance in this confrontation to the side of humans. Nevertheless, the excessive and improper use of antibacterial drugs and the evolution of bacteria has gotten the better of humans again. Therefore, today, the search for new antibacterial drugs or the development of alternative approaches to the prevention and treatment of bacterial infections is relevant and topical again. Vaccination is one of the most effective strategies for the prevention of bacterial infections. The success of new-generation vaccines, such as mRNA vaccines, in the fight against viral infections has prompted many researchers to design mRNA vaccines against bacterial infections. Nevertheless, the biology of bacteria and their interactions with the host's immunity are much more complex compared to viruses. In this review, we discuss structural features and key mechanisms of evasion of an immune response for nine species of bacterial pathogens against which mRNA vaccines have been developed and tested in animals. We focus on the results of experiments involving the application of mRNA vaccines against various bacterial pathogens in animal models and discuss possible options for improving the vaccines' effectiveness. This is one of the first comprehensive reviews of the use of mRNA vaccines against bacterial infections in vivo to improve our knowledge. [ABSTRACT FROM AUTHOR]

Bacteria-based cancer therapy employs various strategies to combat tumors, one of which is delivering tumor-associated antigen (TAA) to generate specific immunity. Here, we utilized a poly-arginine extended HPV E7 antigen (9RE7) for attachment on Salmonella SL7207 outer membrane to synthesize the bacterial vaccine Salmonella-9RE7 (Sal-9RE7), which yielded a significant improvement in the amount of antigen presentation compared to the previous lysine-extended antigen coating strategy. In TC-1 tumor mouse models, Sal-9RE7 monotherapy decreased tumor growth by inducing E7 antigen-specific immunity. In addition, pairing Sal-9RE7 with adjuvant Albumin-IFNβ (Alb-IFNβ), a protein cytokine fusion, the combination significantly increased the antitumor efficacy and enhanced immunogenicity in the tumor microenvironment (TME). Our study made a significant contribution to personalized bacterial immunotherapy via TAA delivery and demonstrated the advantage of combination therapy. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. Salmonella Dublin latent carrier cows represent a high risk for infection of newborn calves via intrauterine transmission and shedding of bacteria in feces and colostrum at calving. Vaccination of these latent carrier dams during late gestation boosts immunity against Salmonella Dublin. This could reduce the activation of the dormant bacteria during the periparturient immune dysfunction period, thereby reducing the risk of early-life infection in the offspring. Thus, the objective of this study was to evaluate the extent to which vaccinating Salmonella Dublin latent carrier cows at dry-off with a commercial live culture vaccine reduces bacterial shedding at calving and intrauterine infection to calves. To identify latent carriers, we screened 1,084 cows in 4 Michigan commercial dairy farms with a history of Salmonella Dublin. Cows were defined as latent carriers when they showed 3 consecutive positive milk antibody ELISA tests conducted every 2 mo. Subsequently, 148 latent carriers were randomly allocated to the vaccine or control group. Vaccine cows received a commercial live culture vaccine s.c. at dry-off and a booster 2 wk later. Control cows received saline s.c. at the same times. At calving, we collected fecal and colostrum samples from the dam and a precolostral serum sample from the calf. Bacterial shedding was evaluated in feces and colostrum both qualitatively and quantitatively through bacterial culture and quantitative PCR (qPCR), respectively. Intrauterine transmission was defined when a calf was positive for serum antibody ELISA at birth. Vaccination decreased the likelihood of calves being born Salmonella Dublin seropositive (relative risk [95% CI]) = 0.19 [0.04–0.84]). However, no Salmonella Dublin positive isolates were identified through either bacteriological culture or qPCR in feces or colostrum. Vaccination of Salmonella Dublin latent carrier cows at dry-off reduced intrauterine transmission to calves. Further research is warranted into the potential of vaccination to decrease vertical transmission of Salmonella Dublin in dairy farms. Additionally, the absence of Salmonella Dublin positive fecal and colostrum samples warrants further evaluation of the detection methods for identifying latent carriers or Salmonella Dublin isolation, as well as the role of latent carriers in infecting newborn calves in the maternity area at birth. [ABSTRACT FROM AUTHOR]

Background: Live viral vector-based vaccines are known to elicit strong immune responses, but their use can be limited by anti-vector immunity. Here, we analyzed the immunological responses of a live-attenuated recombinant Pichinde virus (PICV) vector platform (rP18tri). Methods: To evaluate anti-PICV immunity in the development of vaccine antigen-specific immune responses, we generated a rP18tri-based vaccine expressing the lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) and administered four doses of this rP18tri-NPLCMV vaccine to mice. Using MHC-I tetramers to detect PICV NP38-45 and LCMV NP396-404 epitope-specific CD8+ T cells, we monitored vector- and vaccine-antigen-specific immune responses after each vaccination dose. Results: LCMV NP396-404-specific effector and memory CD8+ T cells were detected after the first dose and peaked after the second dose, whereas PICV NP38-45-specific memory CD8+ T cells increased with each dose. PICV-binding IgG antibodies peaked after the second dose, while anti-PICV neutralizing antibodies (NAbs) remained low even after the fourth dose. Immunization with the rP18tri-NPLCMV vaccine significantly reduced LCMV viral titers in a chronic LCMV Clone 13 infection model, demonstrating the protective role of LCMV NP-specific T cells. Conclusion: These findings provide important insights into the antigen- and vector-specific immunity of the rP18tri-NPLCMV vaccine and support the development of NP-based vaccines against arenavirus pathogens. [ABSTRACT FROM AUTHOR]

Introduction Technological innovations have been instrumental in advancing vaccine design and protective benefit. Improvements in the safety, tolerability, and efficacy/effectiveness profiles have profoundly reduced vaccine-preventable global disease morbidity and mortality. Here we present an original vaccine platform, the Multiple Antigen Presenting System (MAPS), that relies on high-affinity interactions between a biotinylated polysaccharide (PS) and rhizavidin-fused pathogen-specific proteins. MAPS allows for flexible combinations of various PS and protein components.Areas covered This narrative review summarizes the underlying principles of MAPS and describes its applications for vaccine design against bacterial and viral pathogens in non-clinical and clinical settings.Expert opinion The utilization of high-affinity non-covalent biotin–rhizavidin interactions in MAPS allows for combining multiple PS and disease-specific protein antigens in a single vaccine. The modular design enables a simplified exchange of vaccine components. Published studies indicate that MAPS technology may support enhanced immunogenic breadth (covering more serotypes, inducing B- and T-cell responses) beyond that which may be elicited via PS- or protein-based conjugate vaccines. Importantly, a more detailed characterization of MAPS-based candidate vaccines is warranted, especially in clinical studies. It is anticipated that MAPS-based vaccines could be adapted and leveraged across numerous diseases of global public health importance.

Francisella tularensis is one of the several biothreat agents for which a licensed vaccine is needed. To ensure vaccine protection is achieved across a range of virulent F. tularensis strains, we assembled and characterized a panel of F. tularensis isolates to be utilized as challenge strains. A promising tularemia vaccine candidate is rLVS ΔcapB/iglABC (rLVS), in which the vector is the LVS strain with a deletion in the capB gene and which additionally expresses a fusion protein comprising immunodominant epitopes of proteins IglA, IglB, and IglC. Fischer rats were immunized subcutaneously 1-3 times at 3-week intervals with rLVS at various doses. The rats were exposed to a high dose of aerosolized Type A strain Schu S4 (FRAN244), a Type B strain (FRAN255), or a tick derived Type A strain (FRAN254) and monitored for survival. All rLVS vaccination regimens including a single dose of 107 CFU rLVS provided 100% protection against both Type A strains. Against the Type B strain, two doses of 107 CFU rLVS provided 100% protection, and a single dose of 107 CFU provided 87.5% protection. In contrast, all unvaccinated rats succumbed to aerosol challenge with all of the F. tularensis strains. A robust Th1-biased antibody response was induced in all vaccinated rats against all F. tularensis strains. These results demonstrate that rLVS ΔcapB/iglABC provides potent protection against inhalational challenge with either Type A or Type B F. tularensis strains and should be considered for further analysis as a future tularemia vaccine.

Various neurological complications have been linked with vaccines ranging from encephalitis, stroke, ADEM to GBS and many more. Although both viral as well as bacterial vaccines have been reported to cause neurological adverse events, brachial plexitis following vaccination is very uncommon. Vaccination drive against COVID-19 was started on 16th Jan 2021 in India. Various adverse events have been reported following vaccination since then. We observed two cases of brachial plexitis following the first dose of the Covishield vaccine. Although the risk-benefit ratio is very low for the COVID-19 vaccine, it is of vital importance for every clinician to be aware of such a rare adverse event. [ABSTRACT FROM AUTHOR]

Malaria remains a major global health problem. Transmission occurs in 84 countries across five continents, with almost 250 million cases and over 600,000 deaths each year. Primary and secondary care clinicians in the UK need to be alert to the prospect of malaria presenting in returning travellers. They must be aware of the signs of severe malaria, the need for prompt diagnosis and treatment, and the importance of seeking specialist advice. With emerging resistance, climate change and the roll-out of the first malaria vaccines, the landscape of malaria is changing. Here we discuss the past, present and future of malaria. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila causes motile Aeromonas septicemia (MAS), a disease with a high mortality rate in tilapia culture. Feed-based vaccines with the incorporation of inactivated whole-cell bacteria into the feed offer promising tools to control MAS. Currently, the incorporation of genome-free bacteria as bacterial vaccine through the implementation of SimCells® technology into the feed has become a particular interest. Background/Objectives: This study investigates the efficacy of a feed-based vaccine incorporating genome-free A. hydrophila (FBV-GFAH) against MAS infection in red tilapia. Methods: The vaccine was prepared and delivered at 5% fish body weight for three consecutive days in weeks 0 (prime vaccination) and 2 (first booster vaccination), orally. Throughout a five-week experimental period, the immune-related genes (IL-1β, MHC-II, CD4, IgT, and IgM) expression in the hindgut and head kidney of the fish was determined using RT-qPCR assay. Lysozyme (serum) and overall IgM (serum, gut lavage, and skin mucus) productions were also detected. Results: Fish vaccinated with FBV-GFAH showed a significant (p ≤ 0.05) improvement in relative percent survival compared with unvaccinated fish following bacterial challenge. FBV-GFAH induced the expression of immune-related genes in the hindgut and head kidney, especially after booster vaccination. Furthermore, serum lysozyme activity and overall IgM production in serum, skin mucus, and gut lavage were also significantly (p ≤ 0.05) improved in the FBV-GFAH vaccinated fish than the unvaccinated fish. Conclusions: This study showed that FBV-GFAH is a promising feed-based vaccine technology to control MAS in cultured tilapia. [ABSTRACT FROM AUTHOR]

Background: Elderly individuals over 65, along with children under 5, are the most affected by invasive pneumococcal diseases (IPDs). Monitoring vaccination coverage and conducting surveillance are essential for guiding evidence-based prevention campaigns and public health measures. Methods: Since 2007, the Veneto Region has relied on three sources for surveillance of invasive bacterial infections, contributing to an increase in reported IPD cases. This study analyzed notifications related to individuals aged ≥65 years from 2007 to 2023. Results: A total of 1527 cases of IPDs in elderly individuals were reported between 2007 and 2023. The notification rate significantly increased from 5.61 to 14.63 per 100,000 inhabitants, despite underreporting during the COVID-19 pandemic. Cases associated with sepsis increased from 3.89 to 9.58 per 100,000, while notifications of meningitis and case fatality rates remained stable at 1.5 per 100,000 and 11.8%, respectively. Serotyping was not performed in 52% of the notifications. The most common serotypes were 3 (21.6%), 8 (11.1%), and 19A (5.0%), with fluctuations over time. There was a significant decline in serotypes covered by PCV7 and PCV13 and an increase in non-vaccine serotypes. Conclusions: The regional surveillance system allows for an increasingly comprehensive profile of the epidemiological landscape of IPDs in Veneto. However, the surveillance of pneumococcal infections still presents challenges. The currently available data are likely to be underestimated, mainly referring to the most severe cases, and the serotyping necessary to identify the etiological agent is still not often performed. [ABSTRACT FROM AUTHOR]

Background: Brucellosis in livestock and its transmission to humans through the consumption of contaminated dairy products is an important issue. The introduction of new approaches using immunogenic proteins against and diagnosing brucellosis is a serious issue in human health. Methods: Brucella abortus contains five proteins including: MOXR family ATPase-α2, T9SS C-terminal target domain-containing protein, Cobyric acid synthase, Hypothetical protein, and VirB11 type IV Secretion protein, which were considered and the designed recombinant polypeptide was produced and evaluated. The pure recombinant protein ABOR with 549aa in combination with chitin as an adjuvant was injected subcutaneously into guinea pigs to evaluate their immunity responses. Results: The results indicated that the ABOR recombinant protein induced Th1 immunity with high levels of specific IgG (IgG2a) as well as Interferon-γ (IFN-γ), Interleukin- 2 (IL-2), IL-12, and Tumor Necrosis Factor-alpha (TNF-α), compared to the control group. Th1/Th2 ratio analysis demonstrated the efficacy of ABOR protein combined with chitin in stimulating cellular immunity in the animals. Conclusion: Designed recombinant polypeptide combined with chitin showed ability for induction of cellular and humoral immunity an guinea pigs compared to RB51 vaccine. [ABSTRACT FROM AUTHOR]

The bacterium Vibrio vulnificus can cause severe infections internally and externally. The mortality rate of V. vulnificus -associated gangrene and septicemia has increased due to antibiotic resistance and the absence of human vaccine. Bacterial carbohydrates have been widely used in the development of bacterial vaccines. Here, a rare l -Gal p NAmA-containing disaccharide that exists in V. vulnificus biotype 2 serovar A O-antigen was synthesized from d -glucose and l -galactose. An investigation on the influence of different linkers on the disaccharide synthetic efficiency indicated that the amine linker has more practicality. Two α-glycosidic linkages were constructed with good stereoselectivity by using nonparticipating C2 azido group and solvent effect. An orthogonal protection strategy allowed introductions of carboxyl and acetamidino (Am) groups at the disaccharide stage. The synthesis of the amine-linked disaccharide will provide a basis for the preparation of the trisaccharide repeating unit and longer fragments of V. vulnificus biotype 2 serovar A O-antigen, as well as other complex glycans. [ABSTRACT FROM AUTHOR]

Mycoplasma gallisepticum (MG) is an avian respiratory pathogen causing significant global economic losses to the poultry industries. Current live-attenuated and bacterin vaccines provide some measures of protective immunity but exhibit suboptimal efficacy, utility, or safety. To address these shortcomings, we utilized knowledge of MG biology and virulence to develop a subunit vaccine containing recombinantly produced primary adhesin GapA, cytadhesin-related molecule CrmA, and four early-phase-expressed variable lipoprotein hemagglutinins (VlhAs) (3.03, 3.06, 4.07, 5.05) of the virulent strain Rlow. The vaccine was tested in chickens using a subcutaneous dose of 50 µg per protein, a prime-boost schedule, and strain Rlow challenge in multiple studies to compare adjuvant formulations. While different adjuvants resulted in variable levels of protection, only CpG oligodeoxynucleotide (CpG ODN 2007) resulted in significant reductions of both MG recovery and tracheal pathology. These results demonstrate that a rationally designed and safe subunit vaccine is efficacious against MG disease. [ABSTRACT FROM AUTHOR]

Introduction: Antibiotic resistance is regrettably increasing. Recently, application of postbiotics against various microbial pathogens can safely be considered to formulate/substitute with antibiotics. As such, we aimed to investigate the inhibitory effect of Lactobacillus Paracasei against the most common Staphylococcal and coliform pathogens. Methods & Materials: The standard strain of Lactobacillus (L.) paracasei was cultivated in MRS medium. Then, the inhibitory effects of different obtained postbiotics along with negative-and-positive controls on two pathogenic bacteria, Staphylococcus (S.) aureus and Escherichia (E.) coli, was evaluated by the MIC test using the microdilution method on 96-well plates. The results were determined at 630 nm. Results: The effect of all isolated postbiotics except group C (supernatant obtained with sonicationheat shock treatment) compared to the negative controls (without treatment) was statistically significant (p<0.05). Also, the postbiotic group D (supernatant obtained with sonication-thermal shock-freeze treatment) had as remarkably inhibitory effect as positive control (with meropenem treatment) on S. aureus (p=0.0006) and E. coli (P=0.0003). Also, different groups of postbiotics had almost similarly non-significant effect on S. aureus versus E. coli. Conclusion: Results of this study emphasize the antibacterial potential of Lactobacillus paracasei postbiotics against common pathogens, and these postbiotics can be considered as one of the promising candidates for development and further biomedical and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Salmonella is a significant zoonotic foodborne pathogen, and the global spread of multidrug-resistant (MDR) strains poses substantial challenges, necessitating alternatives to antibiotics. Among these alternatives, vaccines protect the community against infectious diseases effectively. This review aims to summarize the efficacy of developed Salmonella vaccines evaluated in various animal hosts and highlight key transitions for future vaccine studies. A total of 3221 studies retrieved from Web of Science, Google Scholar, and PubMed/Medline databases between 1970 and 2023 were evaluated. One hundred twenty-seven qualified studies discussed the vaccine efficacy against typhoidal and nontyphoidal serovars, including live-attenuated vaccines, killed inactivated vaccines, outer membrane vesicles, outer membrane complexes, conjugate vaccines, subunit vaccines, and the reverse vaccinology approach in different animal hosts. The most efficacious vaccine antigen candidate found was recombinant heat shock protein (rHsp60) with an incomplete Freund's adjuvant evaluated in a murine model. Overall, bacterial ghost vaccine candidates demonstrated the highest efficacy at 91.25% (95% CI = 83.69–96.67), followed by the reverse vaccinology approach at 83.46% (95% CI = 68.21–94.1) across animal hosts. More than 70% of vaccine studies showed significant production of immune responses, including humoral and cellular, against Salmonella infection. Collectively, the use of innovative methods rather than traditional approaches for the development of new effective vaccines is crucial and warrants in-depth studies. [ABSTRACT FROM AUTHOR]

Inducing T lymphocyte (T-cell) activation and proliferation with specificity against a pathogen is crucial in vaccine formulation. Assessing vaccine candidates' ability to induce T-cell proliferation helps optimize formulation for its safety, immunogenicity, and efficacy. Our in-house vaccine candidates use microparticles (MPs) and nanoparticles (NPs) to enhance antigen stability and target delivery to antigen-presenting cells (APCs), providing improved immunogenicity. Typically, vaccine formulations are screened for safety and immunostimulatory effects using in vitro methods, but extensive animal testing is often required to assess immunogenic responses. We identified the need for a rapid, intermediate screening process to select promising candidates before advancing to expensive and time-consuming in vivo evaluations. In this study, an in vitro overlay assay system was demonstrated as an effective high-throughput preclinical testing method to evaluate the immunogenic properties of early-stage vaccine formulations. The overlay assay's effectiveness in testing particulate vaccine candidates for immunogenic responses has been evaluated by optimizing the carboxyfluorescein succinimidyl ester (CFSE) T-cell proliferation assay. DCs were overlaid with T-cells, allowing vaccine-stimulated DCs to present antigens to CFSE-stained T-cells. T-cell proliferation was quantified using flow cytometry on days 0, 1, 2, 4, and 6 upon successful antigen presentation. The assay was tested with nanoparticulate vaccine formulations targeting Neisseria gonorrhoeae (CDC F62, FA19, FA1090), measles, H1N1 flu prototype, canine coronavirus, and Zika, with adjuvants including Alhydrogel® (Alum) and AddaVax™. The assay revealed robust T-cell proliferation in the vaccine treatment groups, with variations between bacterial and viral vaccine candidates. A dose-dependent study indicated immune stimulation varied with antigen dose. These findings highlight the assay's potential to differentiate and quantify effective antigen presentation, providing valuable insights for developing and optimizing vaccine formulations. [ABSTRACT FROM AUTHOR]

Infections caused by Gram-negative bacteria are leading causes of mortality worldwide. Due to the rise in antibiotic resistant strains, there is a desperate need for alternative strategies to control infections caused by these organisms. One such approach is the prevention of infection through vaccination. While live attenuated and heat-killed bacterial vaccines are effective, they can lead to adverse reactions. Newer vaccine technologies focus on utilizing polysaccharide or protein subunits for safer and more targeted vaccination approaches. One promising avenue in this regard is the use of proteins released by the Type 5 secretion system (T5SS). This system is the most prevalent secretion system in Gram-negative bacteria. These proteins are compelling vaccine candidates due to their demonstrated protective role in current licensed vaccines. Notably, Pertactin, FHA, and NadA are integral components of licensed vaccines designed to prevent infections caused by Bordetella pertussis or Neisseria meningitidis. In this review, we delve into the significance of incorporating T5SS proteins into licensed vaccines, their contributions to virulence, conserved structural motifs, and the protective immune responses elicited by these proteins. [ABSTRACT FROM AUTHOR]

The article discusses the results of the global phase 3 CLOVER study evaluating PF-06425090, a recombinant detoxified toxin vaccine for Clostridioides difficile infection (CDI). Topics include the study's primary objective of reducing the incidence of primary CDI episodes, which was not met, but demonstrated a reduction in the duration of CDI and related medical interventions; the safety and tolerability of the vaccine; and comparisons to other recent CDI vaccine trials.

Bacterial vaccines have become a crucial tool in combating antimicrobial resistance (AMR) in poultry. The overuse and misuse of antibiotics in poultry farming have led to the development of AMR, which is a growing public health concern. Bacterial vaccines are alternative methods for controlling bacterial diseases in poultry, reducing the need for antibiotics and improving animal welfare. These vaccines come in different forms including live attenuated, killed, and recombinant vaccines, and they work by stimulating the immune system to produce a specific response to the target bacteria. There are many advantages to using bacterial vaccines in poultry, including reduced use of antibiotics, improved animal welfare, and increased profitability. However, there are also limitations such as vaccine efficacy and availability. The use of bacterial vaccines in poultry is regulated by various governmental bodies and there are economic considerations to be taken into account, including costs and return on investment. The future prospects for bacterial vaccines in poultry are promising, with advancements in genetic engineering and vaccine formulation, and they have the potential to improve the sustainability of the poultry industry. In conclusion, bacterial vaccines are essential in combating AMR in poultry and represent a crucial step towards a more sustainable and responsible approach to poultry farming.

[Display omitted] Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F. nucleatum , thereby enhancing cancer treatment. Although adjuvants have been employed to enhance the immune response, the vaccine's effectiveness is constrained by inadequate T-cell activation necessary for eradicating intracellular pathogens. In this study, we developed a minimalistic, biomimetic nanovaccine by integrating highly immunostimulatory adjuvant cholesterol-modified CpG oligonucleotides into the autologously derived F. nucleatum membranes. Compared to the traditional vaccines consisting of inactivated bacteria and Alum adjuvant, the nanovaccine coupled with bacterial membranes and adjuvants could remarkably improve multiple antigens and adjuvant co-delivery to dendritic cells, maximizing their ability to achieve effective antigen presentation and strong downstream immune progress. Notably, the nanovaccine exhibits outstanding selective prophylactic and therapeutic effects, eliminating F. nucleatum without affecting intratumoral and gut microbiota. It significantly enhances chemotherapy efficacy and reduces cancer metastasis in F. nucleatum -infected colorectal cancer. Overall, this work represents the rational application of bacterial nanovaccine and provides a blueprint for future development in enhancing the antitumor effect against bacterial-infected cancer. [ABSTRACT FROM AUTHOR]

Live vaccines are ideal for inducing immunity but suffer from the need to attenuate their pathogenicity or replication to preclude the possibility of escape. Unnatural amino acids (UAAs) provide a strategy to engineer stringent auxotrophies, yielding conditionally replication incompetent live bacteria with excellent safety profiles. Here, we engineer Pseudomonas aeruginosa to maintain auxotrophy for the UAA p-benzoyl-l-phenylalanine (BzF) through its incorporation into the essential protein DnaN. In vivo evolution using an Escherichia coli-based two-hybrid selection system enabled engineering of a mutant DnaN homodimeric interface completely dependent on a BzF-specific interaction. This engineered strain, Pa Vaccine, exhibits undetectable escape frequency (<10−11) and shows excellent safety in naïve mice. Animals vaccinated via intranasal or intraperitoneal routes are protected from lethal challenge with pathogenic P. aeruginosa PA14. These results establish UAA-auxotrophic bacteria as promising candidates for bacterial vaccine therapy and outline a platform for expanding this technology to diverse bacterial pathogens. In this work, authors develop a live vaccine candidate against Pseudomonas aeruginosa using an unnatural amino acid-based auxotrophic strategy. They provide insight on the vaccine's in vivo safety profile and protection of mice against lethal P. aeruginosa challenge. [ABSTRACT FROM AUTHOR]

Safe and effective vaccines have been developed that protect against high-risk strains of HPV, but uptake is relatively low. We previously identified factors such as sexual attitudes and HPV knowledge that impact the intent of Christian parents to vaccinate their children against HPV. We hypothesized that culturally specific interventions in the form of short videos would be effective at improving HPV vaccine intentions and attitudes. We made three short educational videos, one with a Christian focus, one informational about HPV, and one control. Videos were distributed electronically with accompanying surveys, and responses were measured before and after watching a randomly selected video. The religious-focused and educational interventions significantly (p < 0.0001, p = 0.0015) improved intentions towards HPV vaccination. The religiously-focused video also significantly diminished the belief that the HPV vaccine is unnecessary because of a family's values (p = 0.014). Parents significantly credited both interventions with improving their intent to vaccinate their children against HPV (p < 0.001 for both). These results suggest that culturally focused educational interventions are effective at influencing vaccine intentions and attitudes, even when those are based on religious or cultural feelings. Highly specific interventions are likely to be necessary for optimal improvement in vaccine hesitancy. [ABSTRACT FROM AUTHOR]

Objectives: Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores the urgency for innovative strategies, such as immunoinformatics. Consequently, this study aimed to design a targeted multi-epitope vaccine against TB infection utilizing an immunoinformatics approach. Methods: The multi-epitope vaccine targeted Ag85A, Ag85B, ESAT-6, and CFP-10 proteins. The design adopted various immunoinformatics tools for cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitope prediction, the assessment of vaccine characteristics, structure modeling, population coverage analysis, disulfide engineering, solubility prediction, molecular docking/dynamics with toll-like receptors (TLRs), codon optimization/cloning, and immune simulation. Results: The multi-epitope vaccine, which was assembled using 12 CTL, 25 HTL, and 21 LBL epitopes associated with CpG adjuvants, showed promising characteristics. The immunoinformatics analysis confirmed the antigenicity, immunogenicity, and lack of allergenicity. Physicochemical evaluations indicated that the proteins were stable, thermostable, hydrophilic, and highly soluble. Docking simulations suggested high-affinity binding to TLRs, including TLR2, TLR4, and TLR9. In silico immune simulation predicted strong T cell (cytokine release) and B cell (immunoglobulin release) responses. Conclusion: This immunoinformatics-designed multi-epitope vaccine targeting Ag85A, Ag85B, ESAT-6, and CFP-10 proteins showed promising characteristics in terms of stability, immunogenicity, antigenicity, solubility, and predicted induction of humoral and adaptive immune responses. This suggests its potential as a prophylactic and therapeutic vaccine against TB. [ABSTRACT FROM AUTHOR]

The increase in antimicrobial-resistant bacterial strains has highlighted the need for a new vaccine strategy. The primary goal of a candidate vaccine is to prevent disease, by inducing a persistent immunologic memory, through the activation of pathogen-specific immune response. Antibody titer is the main parameter used to assess the immunogenicity of bacterial vaccine candidates and it is the most widely used as a correlate of protection. On the other hand, the antibody titer alone cannot provide complete information on all the activity mediated by antibodies which can only be assessed by functional assays, like the serum bactericidal assay and the opsonophagocytosis assay. However, due to the involvement of many biological factors, these assays are difficult to standardize. Some improvements have been achieved in recent years, but further optimizations are needed to minimize inter- and intra-laboratories variability and to allow the applicability of these functional assays for the vaccine immunogenicity assessment on a larger scale. [ABSTRACT FROM AUTHOR]

In this study, we investigated how Radix pseudostellariae polysaccharide (RPP) enhances the immune response of the inactivated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine through interactions with the microbiome and metabolome. We pretreated sows with 10 mg/kg body weight of RPP via drinking water for 7 days prior to intramuscular injection of the PRRSV vaccine. This significantly increased the concentrations of PRRSV GP5 protein antibody, interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-g. Oral administration of RPP also significantly improved the abundance of beneficial bacteria in the stool, such as Parabacteroides distasonis, Prevotella_copri, Eubacterium_sp., and Clostridium_sp._CAG:226, and decreased the levels of potentially pathogenic bacteria, such as Paraeggerthella and [Clostridium] innocuum, compared to the vaccine alone. These bacterial changes were confirmed using quantitative real-time polymerase chain reaction (Q-PCR). Moreover, RPP treatment significantly increased the blood concentrations of L-theanine, taurodeoxycholic acid (TDCA), and N-arachidonoyl proline, and decreased the levels of L-glutamine, oclacitinib, lipoxin C4, and leukotriene C5 in sows after immunization (p< 0.05). The concentrations of various blood metabolites were validated using sandwich enzyme-linked immunosorbent assay (ELISA), confirming the accuracy of the metabolomics data. Intriguingly, the integration of microbiome and metabolome analyses highlighted the significance of Prevotella_copri and TDCA. We consequently developed a mouse immunity model using GP5 protein and discovered that oral administration of RPP significantly enhanced the levels of GP5 protein antibodies, IL-2, IL-4, IL-10, and IFN-g in mouse serum. It also increased the number of CD3+ and CD3+CD4+ cells in the spleen. Additionally, Prevotella_copri was administered into the large intestine via the anus for 7 days prior to the intramuscular injection of the PRRSV GP5 protein. The results demonstrated a significant increase in TDCA and GP5 antibody concentration in the mouse serum, indicating that RPP modulates Prevotella_copri to elevate its metabolite TDCA, thereby enhancing the GP5 antibody level. In conclusion, oral administration of 10 mg/kg RPP optimizes gut flora diversity and blood metabolites, particularly Prevotella_copri and TDCA, thereby improving the immune response to the inactivated PRRSV vaccine. [ABSTRACT FROM AUTHOR]

Objective To screen and identify new human sperm specific antigen epitopes from candidate sperm-specific antigen epitope peptides using phage display random peptide library technolog and bioinformatics methods. Methods Candidate sperm-specific epitope peptide monomers and trimers were synthesized by solid phase polypeptide synthesis. Dot immunoblotting and enzyme-linked immunosorbent assay (ELISA) were used to detect the immune reaction of the peptides with anti-sperm antibody (ASA) positive serum. ELISA was used to detect antibody titers against candidate sperm-specific epitope peptides in serum of immunized mice. The effects of the sera of the mice immunized with the candidate sperm-specific epitope peptide on human spermatozoa were examined by computer aided sperm analysis. Results High performance liquid chromatography and mass spectrometry showed that the purity and structure of the synthesized candidate sperm-specific epitope peptide were in accordance with the design. Blot and ELISA results indicated that the sperm-specific epitope peptide with the amino acid sequence n-TRRIHRHMTIRR-c and its trimers displayed strong immune response to 17 of 35 ASA positive sera. The serum from mice immunized with the peptide and its trimers significantly attenuated the sperm motility parameters compared with serum from the control group (P < 0. 05), with trimeric-induced decrease in motility parameters being particularly significant. (P<0.01). Conclusion The dodecapeptide with amino acid sequence n-TRRIHRHMTIRR-c is a novel human sperm-specific epitope peptide. [ABSTRACT FROM AUTHOR]

Background: Brucellosis vaccines are designed to induce cellular immunity. An effective brucellosis vaccine could induce both cellular and humoral immunity. Serum Bactericidal Assay (SBA) is an important method for determining vaccine humoral immunity. This study is the first to observe humoral immunity in brucellosis by SBA. Methods: Extracted Brucella abortus (B. abortus) Lipopolysaccharide (LPS) and Outer Membrane Proteins (OMPs) were injected into rabbits. Group 1 was injected with 25 µg of LPS, Group 2 was injected with 50 µg of OMPs, and Group 3 was injected with 1 ml of combined vaccine, 3 times every 2 weeks. The groups were challenged with B. abortus 544 in the second injection. Sera were separated 2 weeks after the last injection. SBA was performed, and each well was streak-cultured into a plate of Brucella agar. A colony count was done for each plate. Results: Results have shown, the third injection of the combined vaccine had the highest titer of 1/64, and the efficacy of the vaccine was 87.71%. Conclusion: As a conclusion, the results of this study showed that LPS and OMP's from B. abortus can provide acceptable immunity. [ABSTRACT FROM AUTHOR]

Ornithobacterium rhinotracheale (ORT) is a gram-negative bacterium that causes respiratory infection in chickens and turkeys. The Co-infection of ORT with other viral or bacterial pathogens results in the development of severe clinical symptoms and significant economic losses. The proportion of ORT strains resistant to the current antibiotics employed in poultry flocks has increased in successive years. Contingent on the source of the isolate. It is recommended that the inactivated wholecell vaccine (bacterin) be administered against multi-drug resistant strains of ORT that are present on poultry farms. In the present study, a formalin-inactivated bacterin formulated with an oil adjuvant (MontanideTM ISA 70 VG) was developed based on a local ORT isolate. A prime-boost regimen was employed for the immunization of specific pathogen-free chicken (SPF) groups. Subsequently, the immunogenic potency of the vaccine candidate was evaluated via ELISA and compared with that of a Nobilis® commercial inactivated ORT vaccine.The safety of the Vaccine was studied following the inoculation of a dose that was twice the recommended dose of the prepared bacterin. The commercial inactivated ORT vaccine and the prepared bacterin both elicited the production of induced specific antibodies after three weeks following the initial vaccination, with this response continuing until 16 weeks postvaccination. The immunization of chickens with the commercial vaccine resulted in a higher level of antibody compared to the experimental vaccine. However, no significant difference (P<0.05) was observed between the treated groups overall. The safety test revealed the absence of any adverse local or systemic reactions were found in chickens throughout the post-vaccination period. The data indicate that the prepared ORT-inactivated vaccine is safe and capable of inducing adequate and longlasting immune responses in experimental SPF chickens. It is imperative to conduct field trials to ensure the efficacy of this vaccine candidate in preventing ORT infection. [ABSTRACT FROM AUTHOR]

Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines. [ABSTRACT FROM AUTHOR]

Background: Pneumonic pasteurellosis in sheep is an important economical disease in Bangladesh where Pasteurella multocida killed vaccine is prescribed as a preventive measure. Objective: The present research was conducted in 20 non-descript native sheep to estimate antibody titre in response to haemorrhagic septicaemia oil adjuvant vaccine by Pasteurella multocida Indirect Antibody Enzyme Linked Immunosorbent Assay. Methodology: This animal study was performed during January to March 2024 at Bangladesh Livestock Research Institute, Savar, Dhaka, Bangladesh. Twenty non-descript native female lamb born to non-immunized mother aged 3 to 4 months was acclimatized for on station experiment. The blood was collected at up to 63 days with seven days’ interval post vaccination. The vaccine seed molecularly identified for capsular sero-grouping by Polymerase Chain Reaction. Results: The seed bacterium was Pasteurella multocida capsular serotype B. The vaccine generated statistically significant (p<0.05) increased level of antibody titer compared to control group from day 14 that peaked at 42 days and starts to decline after 49 days and onwards. The mean ± standard deviation of antibody titre of treatment group was 1.79±0.33. In Levene teat, there was no variance equality in the samples was found. Conclusion: The oil adjuvant Hemorrhagic Septicemia vaccine produced by Livestock Research Institute; Bangladesh contained killed Pasteurella multocida capsular serogroup B. It was found to generate statistically significant antibody response in vaccinated sheep that started to rise from day 14 and peaked at 42 days. After 49 days, it started its declining trend up to the study period (69 days). Investigation of the field isolates and their subsequent immunoinformatic study could generate better knowledge in designing more effective vaccine candidate that would give durable protection. [ABSTRACT FROM AUTHOR]

Vaccines are among the most cost-effective public health measures for controlling infectious diseases. Coxiella burnetii is the etiological agent of Q fever, a disease with a wide clinical spectrum that ranges from mild symptoms, such as fever and fatigue, to more severe disease, such as pneumonia and endocarditis. The formalin-inactivated whole-cell vaccine Q-VAX® contains hundreds of antigens and confers lifelong protection in humans, but prior sensitization from infection or vaccination can result in deleterious reactogenic responses to vaccination. Consequently, there is great interest in developing non-reactogenic alternatives based on adjuvanted recombinant proteins. In this study, we aimed to develop a multivalent vaccine that conferred protection with reduced reactogenicity. We hypothesized that a multivalent vaccine consisting of multiple antigens would be more immunogenic and protective than a monovalent vaccine owing to the large number of potential protective antigens in the C. burnetii proteome. To address this, we identified immunogenic T and B cell antigens, and selected proteins were purified to evaluate with a combination adjuvant (IVAX-1), with or without C. burnetii lipopolysaccharide (LPS) in immunogenicity studies in vivo in mice and in a Hartley guinea pig intratracheal aerosol challenge model using C. burnetii strain NMI RSA 493. The data showed that multivalent vaccines are more immunogenic than monovalent vaccines and more closely emulate the protection achieved by Q-VAX. Although six antigens were the most immunogenic, we also discovered that multiplexing beyond four antigens introduces detectable reactogenicity, indicating that there is an upper limit to the number of antigens that can be safely included in a multivalent Q-fever vaccine. C. burnetii LPS also demonstrates efficacy as a vaccine antigen in conferring protection in an otherwise monovalent vaccine formulation, suggesting that its addition in multivalent vaccines, as demonstrated by a quadrivalent formulation, would improve protective responses.

Engineered outer membrane vesicles (OMVs) derived from Gram-negative bacteria are a promising technology for the creation of non-infectious, nanoparticle vaccines against diverse pathogens. However, antigen display on OMVs can be difficult to control and highly variable due to bottlenecks in protein expression and localization to the outer membrane of the host cell, especially for bulky and/or complex antigens. Here, we describe a universal approach for avidin-based vaccine antigen crosslinking (AvidVax) whereby biotinylated antigens are linked to the exterior of OMVs whose surfaces are remodeled with multiple copies of a synthetic antigen-binding protein (SNAP) comprised of an outer membrane scaffold protein fused to a biotin-binding protein. We show that SNAP-OMVs can be readily decorated with a molecularly diverse array of biotinylated subunit antigens, including globular and membrane proteins, glycans and glycoconjugates, haptens, lipids, and short peptides. When the resulting OMV formulations are injected in mice, strong antigen-specific antibody responses are observed that depend on the physical coupling between the antigen and SNAP-OMV delivery vehicle. Overall, these results demonstrate AvidVax as a modular platform that enables rapid and simplified assembly of antigen-studded OMVs for application as vaccines against pathogenic threats.

The document discusses the importance of neutralizing antibodies in COVID-19 vaccination and the development of effective vaccines. It highlights various methods for detecting neutralizing antibodies, such as virus neutralization tests and surrogate virus neutralization tests. The text also emphasizes the need for ongoing research and development of vaccines to address the evolving nature of the SARS-CoV-2 virus. Additionally, it explores the role of adjuvants in enhancing vaccine immunogenicity and the dynamic relationship between vaccine evaluation methods and development processes. [Extracted from the article]

Background: The outer membrane vesicles (OMVs) produced by Gram-negative bacteria can modulate the immune system and have great potentials for bacterial vaccine development. Results: A highly active Acinetobacter baumannii phage lysin, LysP53, can stimulate the production of OMVs after interacting with A. baumannii, Escherichia coli, and Salmonella. The OMVs prepared by the lysin (LOMVs) from A. baumannii showed better homogeneity, higher protein yield, lower endotoxin content, and lower cytotoxicity compared to the naturally produced OMVs (nOMVs). The LOMVs contain a significantly higher number of cytoplasmic and cytoplasmic membrane proteins but a smaller number of periplasmic and extracellular proteins compared to nOMVs. Intramuscular immunization with either LOMVs or nOMVs three times provided robust protection against A. baumannii infections in both pneumonia and bacteremia mouse models. Intranasal immunization offered good protection in the pneumonia model but weaker protection (20–40%) in the bacteremia model. However, with a single immunization, LOMVs demonstrated better protection than the nOMVs in the pneumonia mouse model. Conclusions: The novel lysin approach provides a superior choice compared to current methods for OMV production, especially for vaccine development. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while nonlipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections. [ABSTRACT FROM AUTHOR]

MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that both cellular (Th1/Th17) and antibody (IgG/IgA) responses to UTI89 were induced in MV140-immunized mice. MV140 vaccination resulted in an early increased clearance of UTI89 viable bacteria in the bladder and urine following transurethral infection. This was accompanied by a highly significant increase in CD4+ T cells in the bladder and an increase in urinary neutrophils. Collectively, our results support that MV140 induces cross-reactive humoral and cellular immune responses and cross-protection against UPEC strains. [ABSTRACT FROM AUTHOR]