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Recombinant mutant holotoxin BoNTs (rBoNTs) are being evaluated as possible vaccines against botulism. Previously, several rBoNTs containing 2–3 amino acid mutations in the light chain (LC) showed significant decreases in toxicity (2.5-million-fold–12.5-million-fold) versus wild-type BoNT/A1, leading to their current exclusion from the Federal Select Agent list. In this study, we added four additional mutations in the receptor-binding domain, translocation domain, and enzymatic cleft to further decrease toxicity, creating 7M rBoNT/A1. Due to poor expression in E. coli, 7M rBoNT/A1 was produced in an endogenous C. botulinum expression system. This protein had higher residual toxicity (LD50: 280 ng/mouse) than previously reported for the catalytically inactive rBoNT/A1 containing only three of the mutations (>10 µg/mouse). To investigate this discrepancy, several additional rBoNT/A1 constructs containing individual sets of amino acid substitutions from 7M rBoNT/A1 and related mutations were also endogenously produced. Similarly to endogenously produced 7M rBoNT/A1, all of the endogenously produced mutants had ~100–1000-fold greater toxicity than what was reported for their original heterologous host counterparts. A combination of mutations in multiple functional domains resulted in a greater but not multiplicative reduction in toxicity. This report demonstrates the impact of production systems on residual toxicity of genetically inactivated rBoNTs. [ABSTRACT FROM AUTHOR]

Accurate computational prediction of B-cell epitopes can greatly enhance biomedical research and rapidly advance efforts to develop therapeutics, monoclonal antibodies, vaccines, and immunodiagnostic reagents. Previous research efforts have primarily focused on the development of computational methods to predict linear epitopes rather than conformational epitopes; however, the latter is much more biologically predominant. Several conformational B-cell epitope prediction methods have recently been published, but their predictive performances are weak. Here, we present a review of the latest computational methods and assess their performances on a diverse test set of 29 non-redundant unbound antigen structures. Our results demonstrate that ISPIPab performs better than most methods and compares favorably with other recent antigen-specific methods. Finally, we suggest new strategies and opportunities to improve computational predictions of conformational B-cell epitopes. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emerging coronavirus that caused coronavirus disease 2019 (COVID-19). Whole-genome tracking of SARS-CoV-2 enhanced our understanding of the mechanism of the disease, control, and prevention of COVID-19. Methods: we analyzed 3368 SARS-CoV-2 protein sequences from Iran and compared them with 15.6 million global sequences in the GISAID database, using the Wuhan-Hu-1 strain as a reference. Results: Our investigation revealed that NSP12-P323L, ORF9c-G50N, NSP14-I42V, membrane-A63T, Q19E, and NSP3-G489S were found to be the most frequent mutations among Iranian SARS-CoV-2 sequences. Furthermore, it was observed that more than 94% of the SARS-CoV-2 genome, including NSP7, NSP8, NSP9, NSP10, NSP11, and ORF8, had no mutations when compared to the Wuhan-Hu-1 strain. Finally, our data indicated that the ORF3a-T24I, NSP3-G489S, NSP5-P132H, NSP14-I42V, envelope-T9I, nucleocapsid-D3L, membrane-Q19E, and membrane-A63T mutations might be responsible factors for the surge in the SARS-CoV-2 Omicron variant wave in Iran. Conclusions: real-time genomic surveillance is crucial for detecting new SARS-CoV-2 variants, updating diagnostic tools, designing vaccines, and understanding adaptation to new environments. [ABSTRACT FROM AUTHOR]

Mayaro virus (MAYV) is an arbovirus first isolated in Trinidad and Tobago in 1954. MAYV is the causative agent of Mayaro fever, which is characterised by high fever, maculopapular rash, myalgia and arthralgia. The potential for chronic arthralgia is of particular clinical concern. Currently, MAYV outbreaks are restricted to South and Central America, with some cases reported in Africa as well as several imported cases in Europe. However, in recent years, MAYV has become a growing global concern due to its potential to emerge into urban transmission cycles. Challenges faced with diagnostics, as well as a lack of specific antivirals or licensed vaccines further exacerbate the potential global health threat posed by MAYV. In this review, we discuss this emerging arboviral threat with a particular focus on the current treatment and vaccine development efforts. Overall, MAYV remains a neglected arbovirus due to its limited area of transmission. However, with the potential of its urbanisation and expanding circulation, the threat MAYV poses to global health cannot be overlooked. Further research into the improvement of current diagnostics, as well as the development of efficacious antivirals and vaccines will be crucial to help prevent and manage potential MAYV outbreaks. [ABSTRACT FROM AUTHOR]

Most national prophylactic HPV vaccination programs started in approximately 2008, with either the bivalent Cervarix HPV16/18 or quadrivalent Gardasil (HPV6/11/16/18) vaccines, which were then followed by introduction of the nonavalent Gardasil 9 (HPV6/11/16/18/ 31/33/45/52/58) vaccine from 2015. Since that time, these products have demonstrated their ability to prevent infection with vaccine-covered HPV types and subsequent development of HPV-related cervical and genital pathologies. The data indicate that vaccination of young girls prior to sexual debut is more effective than vaccination of older HPV+ve women. Although some studies have shown a decline in the prevalence of vaccine-covered HPV types, there are national and regional differences in overall vaccine efficacy. Furthermore, several recently published studies show an increase in the prevalence of non-vaccine-covered HPV types in vaccinated populations, which is indicative of HPV type-replacement. It is also notable that vaccine-related changes in HPV type prevalence spread between vaccinated and unvaccinated women at the same geographical location—presumably via sexual transmission. In conclusion, it is not yet clear what effect dissemination of vaccine-associated changes in HPV type prevalence will have on vaccine efficacy and cervical pathology, particularly in mixed populations of vaccinated and unvaccinated women. However, it is very clear these observations do underscore the need for long-term continuation of cervical screening combined with regular reassessment of testing practices. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional-survey-based study aimed to investigate the severity of side-effects from Coronavirus disease (COVID-19) mRNA (Pfizer, Moderna), viral vector DNA (Oxford-AstraZeneca, J&J/Janssen), inactivated virus (Sinopharm, Sinovac), and other vaccines among healthcare workers (HCWs) in Saudi Arabia, focusing on their impact on work attendance. Methods: A total of 894 HCWs residing in Saudi Arabia participated in this study from March 2023 to May 2023. Participants completed an online questionnaire assessing demographic information, vaccination status, comorbidities, vaccine side-effects, and missed work information after vaccination. Descriptive statistics and chi-square tests were used for data analysis. Results: The majority of participants were female (83.7%) and aged 25–34 years (42.8%). Most participants were predominantly vaccinated with mRNA vaccines. Common side-effects included pain at the injection site, fatigue, fever, and chills. However, no significant association was found between vaccine type, side-effects, and work absenteeism. While demographic factors such as age and healthcare profession did not influence work absenteeism, variations were observed among different racial groups. Conclusion: COVID-19 vaccination among HCWs in Saudi Arabia is associated with common side-effects, but their impact on work attendance is not significant. Understanding these implications can inform strategies to support the healthcare workforce and mitigate the impact on patient care and staffing during the ongoing COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The introduction of a new vaccine into immunization programs represents a significant advancement in the global effort to combat vaccine-preventable diseases. Data from the World Health Organization support that immunization prevents between 2 and 3 million deaths each year across various diseases, underscoring its pivotal role in global health. The present study aims to assess the knowledge, attitudes, and anticipated vaccination practices among health professionals in Central Greece in response to the potential introduction of new Respiratory Syncytial Virus (RSV) vaccination guidelines by the National Vaccines Committee. Among the 450 health professionals solicited for the study, 219 provided responses, yielding a response rate of approximately 55%. A substantial majority (70.3%) accurately identified the vaccine's current availability, and 62.1% were aware of the current recommendation for RSV vaccination in pregnant women. In response to whether health professionals support the inclusion of an RSV vaccine in the national vaccination program if it becomes commercially available and is recommended by the Greek National Immunization Program, general practitioners showed the most support, with an average score of 4.86 (95% CI, 4.69–5.00), followed by pediatricians at 4.76 (95% CI, 4.63–4.89), pulmonologists at 4.68 (95% CI, 4.36–5.00), and obstetricians at 4.33 (95% CI, 3.95–4.71). Concerning general opinions on vaccinations, a high level of agreement was noted among the majority of health professionals, excluding nurses. Pharmacists recorded the highest agreement, with a perfect score of 5 (CI, 5.00–5.00), followed closely by pediatricians at 4.99 (CI, 4.97–5.00), GPs at 4.95 (CI, 4.85–5.00), pulmonologists at 4.93 (CI, 4.83–5.00), obstetricians at 4.74 (CI, 4.42–5.00), and nurses at 3.80 (CI, 3.06–4.54). A tailored approach to education is needed to ensure that healthcare professionals can communicate more effectively about RSV risks and vaccination benefits, fostering a proactive stance towards disease prevention and patient care. In essence, our study underscores the importance of knowledge in shaping a compassionate and responsive healthcare environment, ready to meet the challenges of RSV head-on. [ABSTRACT FROM AUTHOR]

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are largely used in the treatment of both relapsing remitting (RR) and progressive (PR) forms of MS. Although effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and a high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality; this, however, suggested the presence of differences in immune responses driven by age and disease severity. [ABSTRACT FROM AUTHOR]

Vaccination is a critical public health measure for preventing infectious diseases, but its acceptance varies globally, influenced by factors like vaccine hesitancy. This study examines attitudes and vaccination literacy among Kazakh students, providing insights into global immunization strategies. A cross-sectional survey was conducted with 3142 students from various Kazakh universities. The HLS19-VAC instrument assessed vaccination literacy, while additional questions evaluated beliefs and attitudes toward vaccines. Data were analyzed to determine associations between vaccine-related beliefs and literacy. The mean vaccination literacy score was 84.74. Most students agreed on the importance (83.4%), safety (79.1%), effectiveness (80.9%), and religious compatibility (77.8%) of vaccines. Positive beliefs significantly correlated with higher literacy scores. Past vaccination behavior, age, gender, and location showed varied associations, with past vaccination status and higher age showing a positive correlation. Positive beliefs about vaccinations were strongly associated with higher vaccination literacy among Kazakh students. Educational interventions that reinforce positive beliefs may improve vaccination literacy and increase vaccination rates. This study underscores the importance of understanding vaccination attitudes to enhance public health strategies in middle-income countries. [ABSTRACT FROM AUTHOR]

High vaccine wastage can serve as a critical barrier to achieving the gains of vaccination, especially in a country like Nigeria, where data on vaccine wastage are sparsely available. We determined the country-wide vaccine wastage rates and their determinants through a mixed-methods study conducted across 576 health facilities (primary and secondary) in 24 states in Nigeria. We collected facility-based immunization records from June 2018 to May 2019, in addition to healthcare workers' interviews and observations of fixed and outreach sessions. The results show that open-vial wastage ranged from 21.2% (95% CI: 20.2%, 22.2%) for the pentavalent vaccine to 72.6% (95% CI: 71.5%, 73.6%) for BCG. Open-vial wastage rates for BCG, measles, and yellow fever vaccines were higher during outreach sessions, with rates of 76.2%, 64.3%, and 65.2%, respectively. For the outreach and fixed sessions, PCV and Penta had the least wastages of 22.0% for fixed sessions and 20.4% for outreach sessions. This study identified vaccine presentation (liquid vs. lyophilized vaccines), vial size (4 dose vs. 5 dose vs. 10 dose vs. 20 dose), RI service delivery strategies (fixed vs. outreach sessions), number of children vaccinated, and human resources (healthcare workers position/cadre) as key determinants of vaccine wastages in Nigeria. [ABSTRACT FROM AUTHOR]

mRNA vaccines are leading a medical revolution. mRNA technologies utilize the host's own cells as bio-factories to produce proteins that serve as antigens. This revolutionary approach circumvents the complicated processes involved in traditional vaccine production and empowers vaccines with the ability to respond to emerging or mutated infectious diseases rapidly. Additionally, the robust cellular immune response elicited by mRNA vaccines has shown significant promise in cancer treatment. However, the inherent instability of mRNA and the complexity of tumor immunity have limited its broader application. Although the emergence of pseudouridine and ionizable cationic lipid nanoparticles (LNPs) made the clinical application of mRNA possible, there remains substantial potential for further improvement of the immunogenicity of delivered antigens and preventive or therapeutic effects of mRNA technology. Here, we review the latest advancements in mRNA vaccines, including but not limited to target selection and delivery systems. This review offers a multifaceted perspective on this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) caused by bacterial pathogens Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum present significant public health challenges. These infections profoundly impact reproductive health, leading to pelvic inflammatory disease, infertility, and increased susceptibility to other infections. Prevention measures, including antibiotic treatments, are limited by the often-asymptomatic nature of these infections, the need for repetitive and continual screening of sexually active persons, antibiotic resistance for gonorrhea, and shortages of penicillin for syphilis. While vaccines exist for viral STIs like human papillomavirus (HPV) and hepatitis B virus (HBV), there are no vaccines available for bacterial STIs. This review examines the immune responses in the female genital tract to these bacterial pathogens and the implications for developing effective vaccines against bacterial STIs. [ABSTRACT FROM AUTHOR]

In this review article, we aim to provide an overview of fasciolosis in ruminants. Diagnosis through new coprological methods (such as Flukefinder®, FLOTAC®, and Mini-FLOTAC®) remains the most suitable approach for farms. Regarding treatment, there is a scarcity of available drugs, and resistance to them has prompted new approaches (including drug combinations, enhanced metabolism, or the use of natural compounds) to address this issue. Additionally, several researchers have developed vaccines to control the disease, but their efficacy varies, and none are currently sufficient for commercial use. Further studies are needed to better understand all aspects discussed in this manuscript, with the goal of improving diagnosis, treatment, and disease control. It is important to note that this manuscript does not delve into in-depth knowledge of the discussed aspects; rather, it provides an overview of the different methodologies related to these three aspects of parasitic disease. [ABSTRACT FROM AUTHOR]

Peptidyl-prolyl cis/trans isomerases (PPIases) are present in a wide variety of microorganisms, including protozoan parasites such as Trypanosoma cruzi, Trypanosoma brucei, Trichomonas vaginalis, Leishmania major, Leishmania donovani, Plasmodium falciparum, Plasmodium vivax, Entamoeba histolytica, Giardia intestinalis, Cryptosporidium parvum, and Cryptosporidium hominis, all of which cause important neglected diseases. PPIases are classified as cyclophilins, FKBPs, or parvulins and play crucial roles in catalyzing the cis-trans isomerization of the peptide bond preceding a proline residue. This activity assists in correct protein folding. However, experimentally, the biological structure–function characterization of PPIases from these protozoan parasites has been poorly addressed. The recombinant production of these enzymes is highly relevant for this ongoing research. Thus, this review explores the structural diversity, functions, recombinant production, activity, and inhibition of protozoan PPIases. We also highlight their potential as biotechnological tools for the in vitro refolding of other recombinant proteins from these parasites. These applications are invaluable for the development of diagnostic and therapeutic tools. [ABSTRACT FROM AUTHOR]

Background and Objective: An unexpected batch-dependent safety signal for the BNT162b2 mRNA COVID-19 vaccine was recently identified in a nationwide study from Denmark, but the generalizability of this finding is unknown. Therefore, we compared batch-dependent rates of suspected adverse events (SAEs) reported to national authorities in Denmark and Sweden. Materials and Methods: SAE and vaccine batch data were received from national authorities in Denmark and Sweden, and analyses of heterogeneity in the relationship between numbers of vaccine doses and SAEs per batch were performed, along with comparison of SAE rates and severities for batches that were shared between the two countries. Results: Significant batch-dependent heterogeneity was found in the number of SAEs per 1000 doses for both countries, with batches associated with high SAE rates detected in the early phase of the vaccination campaign and positive correlations observed between the two countries for the severity of SAEs from vaccine batches that they shared. Mild SAEs predominated in the batches used in the early part of the vaccination roll-out, where markedly higher SAE rates per 1000 doses in Denmark for the batches that were shared between the two countries suggested that a large proportion of these SAEs were under-reported in Sweden. Conclusions: The batch-dependent safety signal observed in Denmark and now confirmed in Sweden suggests that early commercial batches of BNT162b2 may have differed from those used later on, and these preliminary and hypothesis-generating results warrant further study. [ABSTRACT FROM AUTHOR]

To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Rotavirus remains a significant public health threat, especially in low-income countries, where it is the leading cause of severe acute childhood gastroenteritis, contributing to over 128,500 deaths annually. Although the introduction of the Rotarix and RotaTeq vaccines in 2006 marked a milestone in reducing mortality rates, approximately 83,158 preventable deaths persisted, showing ongoing challenges in vaccine accessibility and effectiveness. To address these issues, a novel subcutaneous vaccine formulation targeting multiple rotavirus genotypes has been developed. This vaccine consists of nine VP8* proteins from nine distinct rotavirus genotypes and sub-genotypes (P[4], P[6], P[8]LI, P[8]LIII, P[8]LIV, P[9], P[11], P[14], and P[25]) expressed in E. coli. Two groups of mice were immunized either with a single immunogen, the VP8* from the rotavirus Wa strain (P[8]LI), or with the nonavalent formulation. Preliminary results from mouse immunization studies showed promising outcomes, eliciting antibody responses against six of the nine immunogens. Notably, significantly higher antibody titers against VP8* P[8]LI were observed in the group immunized with the nonavalent vaccine compared to mice specifically immunized against this genotype alone. Overall, the development of parenteral vaccines targeting multiple rotavirus genotypes represents a promising strategy in mitigating the global burden of rotavirus-related morbidity and mortality, offering new avenues for disease prevention and control. [ABSTRACT FROM AUTHOR]

In recent years, several changes have occurred in the management of chronic immunological conditions with the emerging use of targeted therapies. This two-phase cross-sectional study was conducted through structured in-person interviews in 2018–2019 and 2022. Additional data sources included ambulatory medical records and the itemized reimbursement reporting interface of the National Health Insurance Fund. Drug interactions were analyzed using the UpToDate Lexicomp, Medscape drug interaction checker, and Drugs.com databases. The chi-square test was used, and odds ratios (ORs) were calculated. In total, 185 patients participated. In 53% of patients (n = 53), a serious drug–drug interaction (DDI) was identified (mean number: 1.07 ± 1.43, 0–7), whereas this value was 38% (n = 38) for potential drug–supplement interactions (mean number: 0.58 ± 0.85, 0–3) and 47% (n = 47) for potential targeted drug interactions (0.72 ± 0.97, 0–5) in 2018. In 2022, 78% of patients (n = 66) were identified as having a serious DDI (mean number: 2.27 ± 2.69, 0–19), 66% (n = 56) had a potential drug–supplement interaction (mean number: 2.33 ± 2.69, 0–13), and 79% (n = 67) had a potential targeted drug interactions (1.35 ± 1.04, 0–5). Older age (>60 years; OR: 2.062), female sex (OR: 3.387), and polypharmacy (OR: 5.276) were identified as the main risk factors. Screening methods and drug interaction databases do not keep pace with the emergence of new therapeutics. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the knowledge, attitudes, and behaviors of family physicians (FPs), pediatricians (PPs), and obstetricians and gynecologists (OGs) regarding vaccine administration during pregnancy in Turkey as factors that contribute to decision-making. The survey was distributed among FPs, OGs, and PPs, and participants were asked to rate their knowledge on specific topics using a five-point scale ranging from "Not Effective" to "Effective". The tetanus and diphtheria (Td) vaccine was highly recommended by 94.9% of physicians and considered very effective. Among the physicians surveyed, 80% of PPs and 66.0% of OGs were aware of the disease burden of pertussis. We also found that 74.5% of FPs and 77.2% of PPs believed they needed more information about vaccination during pregnancy. All physicians surveyed agreed or strongly agreed that explaining the disease risks and benefits of vaccination increases the vaccine acceptance rate. The results of this survey study indicate that the knowledge and awareness of physicians need to be improved to increase vaccination rates during pregnancy in Turkey, and it is essential to incorporate influenza and tetanus, diphtheria, and pertussis (TdaP) vaccines into the standard maternal immunization schedule for newborns. [ABSTRACT FROM AUTHOR]

Many vaccines require multiple doses for full efficacy, posing a barrier for patient adherence and protection. One solution to achieve full vaccination may be attained with single-administration vaccines containing multiple controlled release doses. In this study, delayed-release vaccines were generated using atomic layer deposition (ALD) to coat antigen-containing powders with alumina. Using in vitro and in vivo methods, we show that increasing the coat thickness controls the kinetics of antigen release and antibody response, ranging from weeks to months. Our results establish an in vitro–in vivo correlation with a level of tunable control over the antigen release and antibody response times with the potential to impact future vaccine design. [ABSTRACT FROM AUTHOR]

Vaccine-preventable diseases (VPDs) pose a serious public health concern for people living with HIV (PLH). PLH experience a delayed and weakened response to many vaccines available, compared to the general population. Lower seroconversion rates, along with a decreased efficacy and durability of vaccines, increases the susceptibility of PLH to VPDs. Vaccination guidelines specifically targeting this population have been modified to overcome these challenges. However, vaccine uptake remains suboptimal due to multiple barriers, highlighting the need for further studies and the additional implementation of public health measures specifically tailored to PLH. [ABSTRACT FROM AUTHOR]

We previously reported that dendritic cell (DC)-based vaccines targeting antigens expressed by tumor-associated vascular endothelial cells (VECs) and pericytes effectively control tumor growth in translational mouse tumor models. In the current report, we examined whether the therapeutic benefits of such tumor blood vessel antigen (TBVA)-targeted vaccines could be improved by the cotargeting of tumor antigens in the s.c. B16 melanoma model. We also evaluated whether combination vaccines incorporating anti-PD-L1 checkpoint blockade and/or a chemokine-modulating (CKM; IFNα + TLR3-L [rintatolimod] + Celecoxib) regimen would improve T cell infiltration/functionality in tumors yielding enhanced treatment benefits. We report that DC–peptide or DC–tumor lysate vaccines coordinately targeting melanoma antigens and TBVAs were effective in slowing B16 growth in vivo and extending survival, with superior outcomes observed for DC–peptide-based vaccines. Peptide-based vaccines that selectively target either melanoma antigens or TBVAs elicited a CD8+ T cell repertoire recognizing both tumor cells and tumor-associated VECs and pericytes in vitro, consistent with a treatment-induced epitope spreading mechanism. Notably, combination vaccines including anti-PD-L1 + CKM yielded superior therapeutic effects on tumor growth and animal survival, in association with the potentiation of polyfunctional CD8+ T cell reactivity against both tumor cells and tumor-associated vascular cells and a pro-inflammatory TME. [ABSTRACT FROM AUTHOR]

Deamidation is a post-translational chemical modification that occurs within proteins and can be influenced by many factors, including temperature and pH. In vaccines, deamidation is considered undesirable as it may lead to changes in structure, function, stability, and immunogenicity. Detecting deamidation in vaccines, especially adjuvanted vaccines, can be challenging due to the lack of simple quantitative techniques. In this study, the quantification of isoaspartic acid (isoAsp) was used to assess deamidation in model antigens in the presence and absence of common vaccine adjuvants. This study shows that the detection of isoAsp was possible in the presence of various types of adjuvants with little to no interference. High levels of isoAsp were detected in thermally and pH-stressed adjuvanted vaccines, suggesting significant deamidation and highlighting the stability-indicating capabilities of the assay. The quantification of isoAsp in stability programs of a vaccine drug product could possibly find applications in product shelf-life determination, using thermal kinetic modeling to predict deamidation over time. The ability to detect deamidation early in vaccine development enhances process improvements and ultimately improves the vaccine's stability. To summarize, this paper describes a rapid and simple method to determine deamidation in adjuvanted vaccines. This method could be applicable to formulation development, stability assessment, or shelf-life determination. [ABSTRACT FROM AUTHOR]

Aquaculture has rapidly emerged as one of the fastest growing industries, expanding both on global and on national fronts. With the ever-increasing demand for proteins with a high biological value, the aquaculture industry has established itself as one of the most efficient forms of animal production, proving to be a vital component of global food production by supplying nearly half of aquatic food products intended for human consumption. As in classic animal production, the prevention of diseases constitutes an enduring challenge associated with severe economic and environmental repercussions. Nevertheless, remarkable strides in the development of aquaculture vaccines have been recently witnessed, offering sustainable solutions to persistent health-related issues challenging resilient aquaculture production. These advancements are characterized by breakthroughs in increased species-specific precision, improved vaccine-delivery systems, and innovations in vaccine development, following the recent advent of nanotechnology, biotechnology, and artificial intelligence in the -omics era. The objective of this paper was to assess recent developments and milestones revolving around aquaculture vaccinology and provide an updated overview of strengths, weaknesses, opportunities, and threats of the sector, by incorporating and comparatively discussing various diffuse advances that span across a wide range of topics, including emerging vaccine technologies, innovative delivery methods, insights on novel adjuvants, and parasite vaccine development for the aquaculture sector. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis, due to their weakened innate and adaptive immunity, are more prone to frequent and severe vaccine-preventable infections. Moreover, impaired adaptive immunity results in a limited antibody response to vaccines. Despite this suboptimal antibody response, vaccines have proven to be very effective in reducing severe outcomes and deaths in these patients. In the Western world, regulatory authorities and scientific liver societies (e.g., AASLD and EASL) have recommended vaccinations for cirrhotic patients. However, despite these strong recommendations, vaccine coverage remains suboptimal. Improving vaccine effectiveness and safety information, providing comprehensive counseling to patients, fact-checking to combat fake news and disinformation and removing barriers to vaccination for disadvantaged individuals may help overcome the low coverage rate. In view of this, vaccines should be administered early in the course of chronic liver diseases, as their efficacy declines with the increasing severity of the disease. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 new waves are primarily caused by changes to the spike protein (S), which can substantially decrease the efficacy of vaccines. Therefore, we tested several multivalent mRNA-LNP vaccines, targeting the full-length S proteins of different variants, and identified an optimal combination for protection against VOCs in BALB/c mice. The tested formulations included trivalent (WT + BA.5 + XBB.1.5), pentavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1), and octavalent (WT + BA.5 + XBB.1.5 + BQ.1.1 + CH.1.1 + Alpha + Delta + BA.2) vaccines. Among these multivalent vaccines, the pentavalent vaccine showed superior protection for almost all tested variants. Despite this, each multivalent vaccine elicited greater broad-spectrum neutralizing antibodies than the previously evaluated bivalent vaccine (WT + BA.5). Subsequently, we redesigned the multivalent vaccine to efficiently generate neutralizing antibodies against recent VOCs, including EG.5.1. Immunization with the redesigned pentavalent vaccine (WT + EG.5.1 + XBB.1.16 + Delta + BA.5) showed moderate levels of protection against recent Omicron VOCs. Results suggest that the neutralization activity of multivalent vaccines is better than those of the tested bivalent vaccines against WT + BA.5 and WT + EG.5.1. Moreover, the pentavalent vaccine we developed may be highly useful for neutralizing new Omicron VOCs. [ABSTRACT FROM AUTHOR]

Introduction: Currently approved SARS-CoV-2 vaccines have been proven effective in protecting against severe COVID-19; however, they show variable efficacy against symptomatic infection and disease transmission. We studied the breakthrough COVID-19 infection (BTI) after booster vaccination against SARS-CoV-2 in people living with HIV (PWH). Methods: This was a retrospective, single-center, descriptive cohort study involving PWH, who were followed in the HIV Clinic of "Attikon" University Hospital in Athens, Greece. A BTI was defined as a case of laboratory-confirmed COVID-19 occurring at least 14 days after the third (booster) vaccine dose. Results: We studied 733 PWH [males: 89%, mean age: 45.2 ± 11.3 years, mean BMI: 26.1 ± 4.1, HIV stage at diagnosis (CDC classification): A/B/C = 80/9/11%, MSM: 72.6%] with well-controlled HIV infection. At least one comorbidity was recorded in 54% of cases. A history of ≥1 vaccination was reported by 90%, with 75% having been vaccinated with ≥3 vaccines. Four hundred and two (55%) PWH had a history of COVID-19 and 302 (41.2%) had a BTI, with only 15 (3.7%) needing hospitalization. Only one patient was admitted to the ICU, and no death was reported. Regarding BTI after booster dose, increased age (OR = 0.97, 95% CI: 0.96–0.99, per 1-year increase), and COVID-19 infection prior to booster dose (OR = 0.38, 95% CI: 0.21–0.68) were associated with a lower likelihood for BTI, whereas higher BMI (OR = 1.04, 95% CI: 1.01–1.08) and MSM as a mode of HIV transmission were associated with increased risk (OR = 2.59, 95% CI: 1.47–4.56). The incidence rate of total COVID-19 and BTI followed the epidemic curve of the general population, with the highest incidence recorded in June 2022. Conclusions: A significant proportion of PWH with well-controlled HIV infection experienced a BTI, with the majority of them having mild infection. These data, which include the period of Omicron variant predominance, confirm the importance of vaccination in the protection against severe COVID-19. [ABSTRACT FROM AUTHOR]

Simple Summary: Stallion mules are infertile but still able to produce testosterone, which influences undesirable behavior. Surgical castration is required to eliminate testosterone synthesis, which results in pain and the risk of postoperative complications. To the best of our knowledge, there are no existing studies regarding immunocastration as an alternative method for surgical castration in mules. The objective of this study was to evaluate whether a gonadotropin-releasing hormone (GnRH) vaccine could be used as a method of immunocastration in stallion mules via the assessment of anti-GnRH antibody concentration, serum testosterone concentration, clinical adverse effects, and changes in the selected behaviors. Intact and unilateral cryptorchid mules received the GnRH vaccine at weeks 0, 4, and 8. The serum testosterone concentrations in GnRH-vaccinated mules were lower than before vaccination from weeks 6 to 14. Subcutaneous edema adjacent to the injection site was observed in intact mules after the second or third vaccination. The stallion mules responded to the GnRH vaccine, resulting in a temporary decrease in serum testosterone. Based on the results of this study, the GnRH vaccine may be administered as a temporary immunocastration method for stallion mules. Stallion mules have been used as working equids in several countries. Aggressiveness under the influence of testosterone results in the necessity for surgical castration before work training. The gonadotropin-releasing hormone (GnRH) vaccine may be an alternative method for immunocastration in mules. The objective of this study was to evaluate the effect of the GnRH vaccine on anti-GnRH antibody concentration, serum testosterone concentration, clinical adverse effects, and behavioral changes in response to receiving selected physical manipulations from humans. Twenty-five mules were separated into three groups: Control-intact, Control-castrated, and Treatment. The Treatment group was further divided according to condition (intact or unilateral cryptorchid) and age. The Treatment group received 195 µg of the GnRH vaccine intramuscularly at weeks 0, 4, and 8. The anti-GnRH antibody concentrations increased at weeks 6 and 10, and then they gradually decreased to baseline at week 24. The Treatment-intact-young group had the highest concentration of anti-GnRH antibody. The serum testosterone concentrations in the Treatment group were lower than before vaccination from weeks 6 to 14. Subcutaneous edema adjacent to the injection site was detected in the Treatment-intact group after booster vaccination. In conclusion, the mules responded to the GnRH vaccine, which could temporarily suppress testosterone for up to 14 weeks. [ABSTRACT FROM AUTHOR]

An estimation of the proportion of nonsynonymous to synonymous mutation (dn/ds, ω) of the SARS-CoV-2 genome would indicate the evolutionary dynamics necessary to evolve into novel strains with increased infection, virulence, and vaccine neutralization. A temporal estimation of ω of the whole genome, and all twenty-nine SARS-CoV-2 genes of major virulent strains of alpha, delta and omicron demonstrates that the SARS-CoV-2 genome originally emerged (ω ~ 0.04) with a strong purifying selection (ω < 1) and reached (ω ~ 0.85) in omicron towards diversifying selection (ω > 1). A marked increase in the ω occurred in the spike gene from alpha (ω = 0.2) to omicron (ω = 1.97). The ω of the replication machinery genes including RDRP, NSP3, NSP4, NSP7, NSP8, NSP10, NSP13, NSP14, and ORF9 are markedly increased, indicating that these genes/proteins are yet to be evolutionary stabilized and are contributing to the evolution of novel virulent strains. The delta-specific maximum increase in ω in the immunomodulatory genes of NSP8, NSP10, NSP16, ORF4, ORF5, ORF6, ORF7A, and ORF8 compared to alpha or omicron indicates delta-specific vulnerabilities for severe COVID-19 related hospitalization and death. The maximum values of ω are observed for spike (S), NSP4, ORF8 and NSP15, which indicates that the gene-specific temporal estimation of ω identifies specific genes for its super-infectivity and virulency that could be targeted for drug development. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) presents a significant threat to the global swine industry. The development of highly effective subunit nanovaccines is a promising strategy for preventing PRRSV variant infections. In this study, two different types of ferritin (Ft) nanovaccines targeting the major glycoprotein GP5, named GP5m-Ft and (Bp-IVp)3-Ft, were constructed and evaluated as vaccine candidates for PRRSV. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) demonstrated that both purified GP5m-Ft and (Bp-IVp)3-Ft proteins could self-assemble into nanospheres. A comparison of the immunogenicity of GP5m-Ft and (Bp-IVp)3-Ft with an inactivated PRRSV vaccine in BALB/c mice revealed that mice immunized with GP5m-Ft exhibited the highest ELISA antibody levels, neutralizing antibody titers, the lymphocyte proliferation index, and IFN-γ levels. Furthermore, vaccination with the GP5m-Ft nanoparticle effectively protected piglets against a highly pathogenic PRRSV challenge. These findings suggest that GP5m-Ft is a promising vaccine candidate for controlling PRRS. [ABSTRACT FROM AUTHOR]

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or live-attenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. Modern vaccines have evolved to contain purified antigenic subunits, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to these subunit vaccines. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present a repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterisation of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs, have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from human viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious viral diseases and enhancing vaccine efficacy and safety. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry. The complex and highly variable character of the ASFV genome makes vaccine development and disease surveillance extremely difficult. The overall trend in ASFV evolution is towards decreased virulence and increased transmissibility. Factors such as gene mutation, viral recombination, and the strain-specificity of virulence-associated genes facilitate viral variations. This review deeply discusses the influence of these factors on viral immune evasion, pathogenicity, and the ensuing complexities encountered in vaccine development, disease detection, and surveillance. The ultimate goal of this review is to thoroughly explore the genetic evolution patterns and variation mechanisms of ASFV, providing a theoretical foundation for advancement in vaccine and diagnostic technologies. [ABSTRACT FROM AUTHOR]

Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article discussing the delivery of drugs to the lower nasal space (LNS) and upper nasal space (UNS) and their potential benefits. It provides a list of various nasal delivery systems, including OptiNose's Xhance and Onzetra Xsail, which are approved for specific conditions. Other devices mentioned include Satsuma's STS101, AeroPump, PharmaSystems' Metered Nasal Dispenser, MeadWestvaco/Silgan's Mistette MkII Pump, Nemera's SP270+, SipNose, Teleflex's Mucosal Atomisation Device, BD's Accuspray, and Aptar's BiVax and LuerVax. The summary also mentions the target delivery areas and any limitations or issues associated with each device. This document is a valuable resource for library patrons researching nasal delivery systems. [Extracted from the article]

Following up on the first PBPK model for an oral vaccine built for alpha-tocopherol, three peptides are explored in this article to verify if they could support an oral vaccine formulation as adjuvants using the same PBPK modeling approach. A literature review was conducted to verify what peptides have been used as adjuvants in the last decades, and it was noticed that MDP derivatives have been used, with one of them even being commercially approved and used as an adjuvant when administered intravenously in oncology. The aim of this study was to build optimized models for three MDP peptides (MDP itself, MTP-PE, and murabutide) and to verify if they could act as adjuvants for an oral vaccine. Challenges faced by peptides in an oral delivery system are taken into consideration, and improvements to the formulations to achieve better results are described in a step-wise approach to reach the most-optimized model. Once simulations are performed, results are compared to determine what would be the best peptide to support as an oral adjuvant. According to our results, MTP-PE, the currently approved and commercialized peptide, could have potential to be incorporated into an oral formulation. It would be interesting to proceed with further in vivo experiments to determine the behavior of this peptide when administered orally with a proper formulation to overcome the challenges of oral delivery systems. [ABSTRACT FROM AUTHOR]

Pharmacovigilance plays a central role in safeguarding public health by continuously monitoring the safety of vaccines, being critical in a climate of vaccine hesitancy, where public trust is paramount. Pharmacovigilance strategies employed to gather information on adverse events following immunization (AEFIs) include pre-registration data, media reports, clinical trials, and societal reporting. Early detection of AEFIs during clinical trials is crucial for thorough safety analysis and preventing serious reactions once vaccines are deployed. This review highlights the importance of societal reporting, encompassing contributions from community members, healthcare workers, and pharmaceutical companies. Technological advancements such as quick response (QR) codes can facilitate prompt AEFI reporting. While vaccines are demonstrably safe, the possibility of adverse events necessitates continuous post-marketing surveillance. However, underreporting remains a challenge, underscoring the critical role of public engagement in pharmacovigilance. This narrative review comprehensively examines and synthesizes key aspects of virus vaccine pharmacovigilance, with special considerations for specific population groups. We explore applicable legislation, the spectrum of AEFIs associated with major vaccines, and the unique challenges and perspectives surrounding pharmacovigilance in this domain. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer in women and is a leading cause of cancer death in women worldwide. Despite the implementation of multiple treatment options, including immunotherapy, breast cancer treatment remains a challenge. In this review, we aim to summarize present challenges in breast cancer immunotherapy and recent advancements in overcoming treatment resistance. We elaborate on the inhibition of signaling cascades, such as the Notch, Hedgehog, Hippo, and WNT signaling pathways, which regulate the self-renewal and differentiation of breast cancer stem cells and, consequently, disease progression and survival. Cancer stem cells represent a rare population of cancer cells, likely originating from non-malignant stem or progenitor cells, with the ability to evade immune surveillance and develop resistance to immunotherapeutic treatments. We also discuss the interactions between breast cancer stem cells and the immune system, including potential agents targeting breast cancer stem cell-associated signaling pathways, and provide an overview of the emerging approaches to breast cancer stem cell-targeted immunotherapy. Finally, we consider the development of breast cancer vaccines and adoptive cellular therapies, which train the immune system to recognize tumor-associated antigens, for eliciting T cell-mediated responses to target breast cancer stem cells. [ABSTRACT FROM AUTHOR]

Heterologous vaccines, which induce immunity against several related pathogens, can be a very useful and rapid way to deal with new pandemics. In this study, the potential impact of licensed COVID-19 vaccines on cytotoxic and helper cell immune responses against Khosta-2, a novel sarbecovirus that productively infects human cells, was analyzed for the 567 and 41 most common HLA class I and II alleles, respectively. Computational predictions indicated that most of these 608 alleles, covering more than 90% of the human population, contain sufficient fully conserved T-cell epitopes between the Khosta-2 and SARS-CoV-2 spike-in proteins. Ninety percent of these fully conserved peptides for class I and 93% for class II HLA molecules were verified as epitopes recognized by CD8+ or CD4+ T lymphocytes, respectively. These results show a very high correlation between bioinformatic prediction and experimental assays, which strongly validates this study. This immunoinformatics analysis allowed a broader assessment of the alleles that recognize these peptides, a global approach at the population level that is not possible with experimental assays. In summary, these findings suggest that both cytotoxic and helper cell immune protection elicited by currently licensed COVID-19 vaccines should be effective against Khosta-2 virus infection. Finally, by being rapidly adaptable to future coronavirus pandemics, this study has potential public health implications. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) is an emerging flavivirus that represents significant public health challenges, particularly in the Americas, and is a substantial risk to other parts of the world due to its rapid expansion and its established association with neurological disorders, including Guillain–Barré syndrome and an intrauterine fetal infection that can cause microcephaly, blindness, and other congenital neurological complications. To date, no vaccine to prevent ZIKV infections has been approved. Therefore, developing a safe and effective vaccine against this virus is a global health priority. This review analyzes the ZIKV outbreaks, as well as associated neurological complications, its genome, and immunological responses. The current vaccines in development have reported results from preclinical and clinical trials about novel approaches to obtain safer and more effective vaccines and the challenges faced by ZIKV vaccine development. [ABSTRACT FROM AUTHOR]

The elimination of both measles and rubella remains a priority for all 53 Member States of the World Health Organization (WHO) European Region. To provide an update on the epidemiological status of measles and rubella in the Region, we reviewed surveillance data on both diseases for 2023 submitted monthly by national surveillance institutions. We analyzed the cases of measles and rubella for 2023 by age group, case classification, vaccination, hospitalization, and importation status and report on measles-related deaths. In 2023, 60,860 measles cases, including 13 fatal cases, were reported in 41 countries. Most cases (95%; n = 57,584) were reported by six countries: Azerbaijan, Kazakhstan, Kyrgyzstan, Romania, the Russian Federation, and Türkiye. Of the 60,848 cases with data on age, 19,137 (31%) were 1–4 years old and 12,838 (21%) were 5–9 years old. A total of 10,412 (17%) were 20 years and older. The genotypes identified in the Region were largely dominated by D8 variants (n = 1357) and the remainder were B3 variants (n = 221). In 2023, 345 rubella cases were reported by 17 countries, mostly from Poland, Kyrgyzstan, Tajikistan, Türkiye, and Ukraine. A total of 262 cases (76%) were classified as clinically compatible and 79 (23%) were laboratory-confirmed. To achieve the elimination of measles and rubella in the Region, political commitment needs to be revived to enable urgent efforts to increase vaccination coverage, improve surveillance and outbreak preparedness, and respond immediately to outbreaks. [ABSTRACT FROM AUTHOR]

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8+ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8+ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8+ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8+ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Early studies have found that the initial COVID-19 vaccination series was protective against severe symptoms and long COVID. However, few studies have explored the association of booster doses on severe disease outcomes and long COVID. This cross-sectional analysis used data from the 2022 US National Health Interview Survey data to investigate how vaccination status correlates with COVID-19 infection severity and long COVID among previously infected individuals. Participants were categorized into three groups: those who had received at least one booster, those with only the initial complete vaccination series, and those with either an incomplete series or no vaccinations. Out of 9521 survey respondents who reported a past positive COVID-19 test, 51.2% experienced moderate/severe infections, and 17.6% experienced long COVID. Multivariable regression models revealed that receiving at least one booster shot was associated with lower odds of experiencing moderate/severe symptoms (aOR = 0.78, p < 0.001) compared to those unvaccinated or with an incomplete series. Additionally, having at least one booster reduced long COVID odds by 24% (aOR = 0.76, p = 0.003). Completing only the primary vaccine series did not significantly decrease the likelihood of severe illness or long COVID. These findings support the continued promotion of booster vaccinations to mitigate long COVID risks in vulnerable populations. [ABSTRACT FROM AUTHOR]

An outbreak of camelpox occurred in the Mangistau region of Kazakhstan in 2019. To control the outbreak of camelpox and to prevent its further spread to other regions, camels were vaccinated using live and inactivated camelpox vaccines produced in Kazakhstan. To evaluate the efficacy of these camelpox vaccines in the field, vaccine trials used 172 camels on camel farms in the Beineu district. Of these, 132 camels were vaccinated using a live attenuated camelpox vaccine and 40 camels were vaccinated using an inactivated vaccine to observe immunogenicity and safety. The live vaccine was inoculated into camels by scarification at a dose of 5 × 104 EID50, and the inactivated vaccine was injected intramuscularly at 5 mL twice, with an interval of 35 days. During the safety evaluation, camels administered either vaccine displayed no clinical signs of illness or any adverse effects. Post-vaccination seroconversion demonstrated that the live attenuated vaccine started to elicit antibody responses in some animals as early as day seven, while, by day 28, 99% of vaccinated camels responded. For camels immunized with the inactivated vaccine, seroconversion began on day 21 at low titers ranging from 1:2 to 1:4. Ninety days post vaccination, 77% of the camels demonstrated an immune response that was up to a titer of 1:16. The antibody response waned six months post vaccination in camels vaccinated with two types of vaccine. Nonetheless, both vaccines were 100% effective at preventing clinical disease in vaccinated camels during the camelpox outbreak. All unvaccinated camels became ill, with manifestations of clinical signs characteristic of camelpox. Following these successful field trials in Kazakhstan, a vaccination program for camels, to control camelpox using the domestically produced live attenuated camelpox vaccine, has started. [ABSTRACT FROM AUTHOR]

Graphene, a two-dimensional material consisting of a single layer of carbon atoms arranged in a honeycomb lattice, has shown great potential in various fields, including biomedicine. When it comes to vaccine development, graphene can offer several advantages due to its unique properties. Potential applications of graphene in vaccine development include improved vaccine delivery, adjuvant properties, improved vaccine stability, improved immune response, and biosensing capabilities. Although graphene offers many potential benefits in vaccine development, there are also some drawbacks and challenges associated with its use. Although graphene shows promising potential for vaccine development, overcoming the challenges and limitations associated with its use is critical to realizing its full potential in the field of immunization. Further research and development efforts are needed to overcome these drawbacks and take advantage of graphene for improved vaccine formulations. In this review, we focus on the advantages and disadvantages of graphene for vaccine development. [ABSTRACT FROM AUTHOR]

This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose–chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization. [ABSTRACT FROM AUTHOR]

The Expanded Programme on Immunization (EPI) and Vaccine Preventable Disease (VPD) Surveillance (VPDS) programs generate multiple data sources (e.g., routine administrative data, VPD case data, and coverage surveys). However, there are challenges with the use of these siloed data for programmatic decision-making, including poor data accessibility and lack of timely analysis, contributing to missed vaccinations, immunity gaps, and, consequently, VPD outbreaks in populations with limited access to immunization and basic healthcare services. Data triangulation, or the integration of multiple data sources, can be used to improve the availability of key indicators for identifying immunization coverage gaps, under-immunized (UI) and un-immunized (zero-dose (ZD)) children, and for assessing program performance at all levels of the healthcare system. Here, we describe the data triangulation processes, prioritization of indicators, and capacity building efforts in Bangladesh, Nigeria, and Rwanda. We also describe the analyses used to generate meaningful data, key indicators used to identify immunization coverage inequities and performance gaps, and key lessons learned. Triangulation processes and lessons learned may be leveraged by other countries, potentially leading to programmatic changes that promote improved access and utilization of vaccination services through the identification of UI and ZD children. [ABSTRACT FROM AUTHOR]

Inactivated and live attenuated vaccines are the mainstays of preventing viral poultry diseases. However, the development of recombinant DNA technology in recent years has enabled the generation of recombinant virus vector vaccines, which have the advantages of preventing multiple diseases simultaneously and simplifying the vaccination schedule. More importantly, some can induce a protective immune response in the presence of maternal antibodies and offer long-term immune protection. These advantages compensate for the shortcomings of traditional vaccines. This review describes the construction and characterization of primarily poultry vaccine vectors, including fowl poxvirus (FPV), fowl adenovirus (FAdV), Newcastle disease virus (NDV), Marek's disease virus (MDV), and herpesvirus of turkey (HVT). In addition, the pathogens targeted and the immunoprotective effect of different poultry recombinant virus vector vaccines are also presented. Finally, this review discusses the challenges in developing vector vaccines and proposes strategies for improving immune efficacy. [ABSTRACT FROM AUTHOR]

Bovine alphaherpesvirus 1 (BoAHV-1) infection affects the production and reproductive performance of dairy and beef livestock, resulting in considerable economic losses. In addition to biosecurity measures, vaccination programs are effective strategies for controlling and preventing BoAHV-1 infection and transmission. We evaluated the serological immune response against BoAHV-1 induced by eight different formulations of commercial vaccines: three modified live vaccines and five killed vaccines containing BoAHV type 1 or types 1 and 5. In the first experiment, 50 BoAHV-1-seronegative guinea pigs were assigned to eight groups; each individual in the treatment groups received two doses (one-fifth of the bovine dose). The second experiment was conducted using 29 crossbred Holstein × Gir heifers in four groups of six to nine animals each. The serological immune response against BoAHV-1 was measured using virus neutralization and enzyme-linked immunosorbent assays to measure the total IgG against BoAHV. We evaluated the effects of the vaccine, time, and interaction of the vaccine and time on neutralizing antibodies against BoAHV-1. Killed vaccines produced low levels of antibodies against BoAHV-1, whereas modified live vaccines produced high levels of antibodies capable of providing neutralizing titers in the vaccinated animals, with the thermosensitive modified live vaccine showing the highest levels of antibodies. [ABSTRACT FROM AUTHOR]