Vaccine Formulations Research Articles

Efficacy of LaAg Vaccine Associated with Saponin Against Leishmania amazonensis Infection

Background/Objectives: The total lysate of Leishmania amazonensis (LaAg) is one of the most extensively studied vaccine formulations against leishmaniasis. Despite demonstrating safety and immunogenicity when administered intramuscularly, LaAg has failed to show efficacy in clinical trials and, in some cases, has even been associated with an enhanced susceptibility to infection. Adjuvants, which are molecules or compounds added to antigens to enhance the immunogenicity or modulate the immune response, are frequently employed in vaccine studies. This study aimed to evaluate different adjuvants to improve the protective efficacy of LaAg in L.amazonensis infection using a BALB/c mouse model. Methods: BALB/c mice were immunized with LaAg in combination with various adjuvants. The delayed-type hypersensitivity (DTH) test was assessed by measuring the infected paw and was used to evaluate the immunogenicity and to determine the most effective adjuvant. The immune response was analyzed through flow cytometry, focusing on cytokine production, immune cell recruitment and lesion size, alongside the control of parasite load at the infection site. The expression levels of iNOS and TGF-β were quantified using RT-qPCR, while IgG1, IgG2a and IgE antibody levels were determined via ELISA. Results: Among the adjuvants tested, only saponin (SAP) elicited a significant DTH response following LaAg challenge. SAP enhanced the immunogenicity of LaAg, as evidenced by increased IFN-γ-producing CD4+ and CD8+ T cells in the draining lymph nodes at 18 h post-challenge. Additionally, SAP facilitated the recruitment of lymphocytes, macrophages, neutrophils and eosinophils to the infection site. Conclusions: The LaAg + SAP combination conferred partial protection, as demonstrated by a reduction in lesion size and the partial control of parasite load. In conclusion, the addition of SAP as an adjuvant to LaAg effectively modulates the immune response, enhancing the vaccine’s protective efficacy. These findings provide valuable insights into the development of improved vaccines against L.amazonensis infection.

New High-Throughput Method for Aluminum Content Determination in Vaccine Formulations

Objective: This manuscript describes an innovative, non-destructive, high-throughput method for the quantification of aluminum hydroxide in aluminum-adjuvanted vaccines, eliminating the need of reagents and providing real-time results. The method is based on a spectrophotometric principle, and several model proteins were studied and tested with the aim to simulate the behavior of aluminum-adjuvanted antigens. Methods: As a proof of concept, the MenB vaccine was used, and the titration of aluminum hydroxide (AH) with ethylenediaminetetraacetic acid (EDTA) was used as an orthogonal reference, as it is one of the current release methods for the content determination of aluminum-hydroxide-adjuvanted vaccine drug products (DPs). The factors influencing the spectrophotometric analysis, such as different plate 96/well containers, variation in the sedimentation of the suspension due to component addition errors during formulation, and batch-to-batch variation were studied to assess the method’s robustness. Five concentration levels (ranging from 2.0 to 4.0 mg/mL AH) with two different batches of aluminum hydroxide were each measured with independent preparations performed by three different operators, for a total of four sessions/operator and 20 formulations/session. An in-depth statistical study was carried out with generated data to assess the precision (in terms of intermediate precision and repeatability), accuracy, linearity, and specificity of the method. Results: The novel spectrophotometric method and the official release one (potentiometric) yielded comparable results, demonstrating the potential of this new method as a release test for AH-adjuvanted products. A simple calibration curve enabled the measurement of samples in a 96-well plate in just a few minutes. Conclusions: We developed a novel method for Aluminum concentration determination in Aluminum-containing pharmaceutical products, like alum-adjuvanted vaccines. This method is fast, completely automatable, and as precise and accurate as already-in-place release methods.

Comparative evaluation of protective efficacy of experimental inactivated vaccines against haemorrhagic septicaemia.

Developing an effective vaccine for haemorrhagic septicaemia (HS) in cattle and buffaloes is urgently needed. While preferred for their safety, achieving sufficient, cross-protective, and long-lasting immunity is still challenging when administering inactivated vaccines. This study aimed to assess the efficacy of four inactivating components comprising three inactivating agents: (1) Binary ethylenimine (BEI), (2) Formalin, (3) a combination of BEI and Formalin, and (4) Hydrogen peroxide (H2O2), in inactivating Pasteurella multocida to enhance HS vaccine potency. H2O2 demonstrated the fastest inactivation kinetics, killing Pasteurella multocida within a few minutes. The combination of BEI and Formalin showed relatively rapid inactivation compared to Formalin or BEI alone. BEI, known for targeting nucleic acids with minimal impact on protein integrity, showed promise but required higher concentrations (8 mM) and a longer duration (16h) for complete inactivation. Based on the inactivation kinetics, 8 mM BEI, 0.1% Formalin, 8 mM BEI + 0.1% Formalin, and 1% H2O2 were chosen for the experimental vaccine formulations. The inactivated Pasteurella multocida were adjuvanted with Montanide ISA-201 oil adjuvant and evaluated in mice model. All vaccine formulations elicited protective responses of over 6.5 log10 units, indicating the high potency of the vaccine formulations. Notably, the vaccine prepared with an H2O2 inactivating agent elicited protection of > 8 log10 units. Our study concludes that H2O2, with its rapid inactivation kinetics and safety profile, presents a promising alternative inactivating agent for HS vaccine development. Future studies should evaluate the protective efficacy of H2O2-inactivated vaccines in target animals.

Nanoparticles as Delivery Vehicles for Vaccines: The Use of Gold Nanoparticles.

Since their inception, therapeutic or prophylactic vaccines have emerged as promising candidates for the prevention or treatment of infections and various diseases, including cancer and autoimmune disorders. In recent times, gold nanoparticles (GNPs) have acquired active roles in the field of vaccine development due to their intrinsic capacity to adjust and enhance the immune response. Due to their characteristics, GNPs can exert optimal effects as both delivery vehicles and adjuvants. Despite their significant importance in vaccinology, numerous obstacles need to be overcome before GNPs can be used in the formulations of vaccines in clinical settings. The current review summarizes the latest and successful use of gold nanoparticles as a viable method for developing a new generation of vaccines.

Exploring How Adipose Tissue, Obesity, and Gender Influence the Immune Response to Vaccines: A Comprehensive Narrative Review.

Vaccines represent an essential tool for the prevention of infectious diseases. Upon administration, a complex interaction occurs between the vaccine formulation and the recipient's immune system, ultimately resulting in protection against disease. Significant variability exists in individual and population responses to vaccination, and these differences remain the focus of the ongoing research. Notably, well-documented factors, such as age, gender, and genetic predisposition, influence immune responses. In contrast, the effects of overweight and obesity have not been as thoroughly investigated. The evidence indicates that a high body mass index (BMI) constitutes a significant risk factor for infections in general, with adipose tissue playing a crucial role in modulating the immune response. Furthermore, suboptimal levels of vaccine seroconversion have been observed among individuals with obesity. This review provides a plausible examination of the immunity and protection conferred by various vaccines in individuals with an overweight status, offering a comprehensive analysis of the mechanisms to enhance vaccination efficiency.

The Development of Opioid Vaccines as A Novel Strategy for the Treatment of Opioid Use Disorder and Overdose Prevention.

Opioid use disorder (OUD) affects over 40 million people worldwide, creating significant social and economic burdens. Medication for opioid use disorder (MOUD) is often considered the primary treatment approach for OUD. MOUD, including methadone, buprenorphine, and naltrexone is effective for some, but its benefits may be limited by poor adherence to treatment recommendations. Immunopharmacotherapy offers an innovative approach by using vaccines to generate antibodies that neutralize opioids, blocking them from crossing the blood-brain barrier and reducing their psychoactive effects. To date, only three clinical trials for opioid vaccines have been published. While these studies demonstrated the potential of opioid vaccines for relapse prevention, there is currently no standardized protocol for evaluating their effectiveness. We have reviewed recent preclinical studies that demonstrated the efficacy of vaccines targeting opioids, including heroin, morphine, oxycodone, hydrocodone, and fentanyl. These studies showed that vaccines against opioids reduced drug reinforcement, decreased opioid-induced antinociception, and increased survival rates against lethal opioid doses. These studies also demonstrated the importance of vaccine formulation and the use of adjuvants in enhancing antibody production and specificity. Finally, we highlighted the strengths and concerns associated with the opioid vaccine treatment, including ethical considerations.

ALC-0315 Lipid-Based mRNA LNP Induces Stronger Cellular Immune Responses Postvaccination.

At the end of 2019, SARS-CoV-2 emerged and rapidly spread, having a profound negative impact on human health and socioeconomic conditions. In response to this unprecedented global health crisis, significant advancements were made in the mRNA vaccine technology. In this study, we have compared the difference between two SARS-CoV-2 receptor-binding domain (RBD) mRNA-Lipid nanoparticle (LNP) vaccines prepared from two different ionizable cationic lipids: ALC-0315 and MC3. Characterization of RBD mRNA-LNPs showed that both MC3-LNP and ALC-0315-LNP are highly uniform and stable. Furthermore, we assessed the humoral immune response in mice after immunization; our findings indicated that both vaccine formulations effectively enhanced the formation and differentiation of germinal center (GC). Notably, the mice immunized with the ALC-0315-LNP vaccine elicited higher levels of IgG and its subclasses and significantly enhanced the activation of dendritic cells and T cells in draining lymph nodes (dLNs) compared to those immunized with the MC3-LNP vaccine. Further analysis of the T cell phenotype after splenic restimulation showed that mice injected with both LNP mRNA vaccines had significantly increased activation of the splenic T cells and Th1-type cytokine production. In addition, our finding showed that both LNP mRNA vaccines significantly increased the proportions of follicular helper T cells (Tfh) and long-lasting plasma cells in the dLNs of mice on day 14 postimmunization compared to control. In conclusion, both ALC-0315 and MC3 exhibited good stability and immunogenicity as mRNA-LNP recipes, but the ALC-0315-based mRNA-LNP vaccine showed higher efficacy in humoral and cellular immune responses compared to MC3.

Optimizing Tongue Fluid Sampling and Testing Protocols for Enhanced PRRSV Isolation from Perinatal Swine Mortalities.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major concern for swine health. Isolating PRRSV is essential for identifying infectious viruses and for vaccine formulation. This study evaluated the potential of using tongue fluid (TF) from perinatal piglet mortalities for PRRSV isolation. Four collection protocols were tested: extracting TF from fresh tissues using phosphate-buffered saline (PBS group), extracting TF from fresh tissues using virus transportation medium (VTM group), extracting TF from freeze-thawed tissue (freeze-thaw group), and using tissue homogenates (homogenate group). Two cell lines (ZMAC and MARC-145) and primary alveolar macrophages (PAM) were evaluated for their effect on successful PRRSV isolation. An eligible PRRSV-positive unstable breeding herd in Midwestern USA was chosen for the study. Tongues were collected in 20 batches (~30 mortalities per batch). Within each batch, each tongue tissue was cut into four quarters, with each quarter randomly assigned to one of the four collection protocols and RT-qPCR tested. Virus isolation (VI) was attempted on 10 batches. The mean RT-qPCR cycle threshold (Ct) values for the PBS, VTM, freeze-thaw, and homogenate groups were 21.9, 21.8, 22.6, and 24.8, respectively. The VI success rate was 22.6%, 12.1%, 2.8%, and 2.8% in the PBS, VTM, freeze-thaw, and homogenate groups, respectively. The probability of successful VI was 3.1% and 21.0% in the MARC-145 and ZMAC cell lines, respectively, and 4.8% in the PAM cells. TF from perinatal mortalities is an option for PRRS VI, aiding in PRRSV monitoring and control programs.

Strong immune responses and robust protection following a novel protein in adjuvant tuberculosis vaccine candidate

BCG remains the only licensed vaccine for tuberculosis (TB), but its efficacy wanes over time. Subunit vaccines, aim to improve BCG immunity and protection, by inducing responses to a few mycobacterial antigens delivered with a specific platform. Since the platform shapes the immune response induced, selecting the right platform has been challenging due to the lack of immune correlates of protection. Recently, the protein-adjuvated subunit vaccine. M72/AS01E, demonstrated 49.7% efficacy in preventing active TB in latently infected adults, indicating that protective immunity through subunit vaccines is possible. In this study we evaluated the immunogenicity and efficacy of the promising mycobacterial antigen PPE15, formulated with five adjuvants developed by the Vaccine Formulation Institute. While all adjuvants were immunogenic, PPE15 with LMQ protected vaccinated mice against an in vivo Mycobacterium tuberculosis challenge, both as a standalone vaccine and as a boost to BCG. Vaccinated mice had enriched lung parenchymal antigen-specific CD4 + CXCR3 + KLRG1− T cells previously associated with TB protection. Heterologous vaccination strategies were also explored by combining intranasal ChAdOx1.PPE15 viral vector, with intramuscular PPE15-LMQ resulting in improved protection compared to individual vaccines. These findings support the progression of this vaccine candidate to the next stages of development.

Retraction Notice to "New relapse of multiple sclerosis and neuromyelitis optica as a potential adverse event of AstraZeneca AZD1222 vaccination for COVID-19" [Multiple Sclerosis and Related Disorders 57 (2022) 103321

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the authors. The authors would like to express their deepest apologies for the error contained in their article and for any concerns or misunderstandings it may have caused. Specifically, the article mistakenly mentioned the presence of the MF59 adjuvant in the AZD1222 vaccine formulation, which is incorrect.

Assessment of heat-killed E. coli expressing Chikungunya virus E2 protein as a candidate vaccine for dual protection against Chikungunya virus and E. coli.

The Chikungunya virus (CHIKV) is a mosquito-borne virus with a long history of recurring epidemics transmitted through Aedes mosquitoes. The rapid spread of CHIKV has intensified the need for potent vaccines. Escherichia coli (E.coli), a vital part of human gut microbiota, is utilized in recombinant DNA technology for cloning. However, its high adaptability can lead to severe infections in humans. This study aimed to develop the candidate dual vaccine against CHIKV and E. coli. For this, we expressed the CHIKV E2 protein in the E. coli Rosetta Bl21 cells and the protein expression was confirmed by western blotting. The IgG immune response of the candidate vaccine was determined against CHIKV and E. coli by ELISA. Further, the potential of antibodies to neutralize CHIKV was evaluated via Tissue Culture Infectious Dose 50 (TCID50). We observed that cells expressing E2 protein with alum immunized mice serum showed a five-fold higher IgG immune response against CHIKV, compared to control cells. The CHIKV neutralization assay results showed a two-fold decrease in CHIKV TCID50 value after 12 hours and a three-fold reduction after 120 hours. Similarly, the vaccine formulation also elicited a significantly higher IgG immune response against E. coli. The results suggested that expressing CHIKV E2 protein in E. coli is a potential approach for generating an IgG immune response against CHIKV and E. coli both. This study proposes a faster, safer, and cost-effective recombinant protein-based vaccine development.

Pivotal role of Helicobacter pylori virulence genes in pathogenicity and vaccine development.

One of the most prevalent human infections is Helicobacter pylori (H. pylori), which affects more than half of the global population. Although H. pylori infections are widespread, only a minority of individuals develop severe gastroduodenal disorders. The global resistance of H. pylori to antibiotics has reached concerning levels, significantly impacting the effectiveness of treatment. Consequently, the development of vaccines targeting virulence factors may present a viable alternative for the treatment and prevention of H. pylori infections. This review aims to provide a comprehensive overview of the current understanding of H. pylori infection, with a particular focus on its virulence factors, pathophysiology, and vaccination strategies. This review discusses various virulence factors associated with H. pylori, such as cytotoxin-associated gene A (cagA), vacuolating cytotoxin gene (vacA), outer membrane proteins (OMPs), neutrophil-activated protein (NAP), urease (ure), and catalase. The development of vaccines based on these virulence characteristics is essential for controlling infection and ensuring long-lasting protection. Various vaccination strategies and formulations have been tested in animal models; however, their effectiveness and reproducibility in humans remain uncertain. Different types of vaccines, including vector-based vaccines, inactivated whole cells, genetically modified protein-based subunits, and multiepitope nucleic acid (DNA) vaccines, have been explored. While some vaccines have demonstrated promising results in murine models, only a limited number have been successfully tested in humans. This article provides a thorough evaluation of recent research on H. pylori virulence genes and vaccination methods, offering valuable insights for future strategies to address this global health challenge.

Yavar-70A, a novel water-in-oil adjuvant: A potency study in HPV-16E7d vaccine model.

Adjuvants are some of the most important components used for vaccine formulation. In addition, the efficacy of vaccines is highly dependent on the nature of the adjuvants used. Therefore, new adjuvant formulations may help develop more potent vaccines. In the present study, the potency of an in-house and water-in-oil adjuvant (Yavar-70A) was compared with Montanide ISA 206 and Montanide ISA 266 in an HPV-16E7d vaccine model. Three HPV-16 E7d vaccines were formulated using three different adjuvants, Montanide ISA 206, Montanide ISA 266, and Yavar-70A, with standard protocols. Afterward, each formulation containing 10 μg of the E7d protein was administered thrice at two-week intervals to C57BL/6 mice. Serum levels of IFN-γ and IL-4 cytokines secreted from spleen cells, total IgG, and specific IgG1 and IgG2a isotypes were assessed using ELISA two weeks after the last immunization. Lymphocyte proliferative responses were also evaluated using the BrdU method. The results indicated that the vaccine formulated using the Yavar-70A adjuvant showed the highest lymphocyte proliferation responses compared with other groups and higher IFN-γ cytokine release compared with that formulated using Montanide ISA 206. However, the vaccine formulated using Montanide ISA 206 induced the highest total IgG responses compared with other groups. Importantly, the vaccine formulated using Yavar-70A decreased IL-4 secretion compared with other vaccinated groups. The present study demonstrated that Yavar-70A induces cellular and humoral immunologic parameters against the HPV-16 E7d vaccine model comparable to commercialized oil-based adjuvants.

Immunoinformatics design of a novel multiepitope vaccine candidate against non-typhoidal salmonellosis caused by Salmonella Kentucky using outer membrane proteins A, C, and F.

The global public health risk posed by Salmonella Kentucky (S. Kentucky) is rising, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans. In this study, we used a bioinformatics approach to develop a peptide-based vaccine targeting epitopes from the outer membrane proteins A, C, and F of S. Kentucky. Additionally, we employed flagellin protein (fliC) from Salmonella Typhimurium (S. Typhimurium) as an adjuvant to enhance the vaccine's effectiveness. Through this approach, we identified 14 CD8+ and 7 CD4+ T-cell epitopes, which are predicted to be restricted by various MHC class I and MHC class II alleles. The predicted epitopes are expected to achieve a population coverage of 94.91% when used in vaccine formulations. Furthermore, we identified seven highly immunogenic linear B-cell epitopes and three conformational B-cell epitopes. These T-cell and B-cell epitopes were then linked using appropriate linkers to create a multi-epitope vaccine (MEV). To boost the immunogenicity of the peptide construct, fliC from S. Typhimurium was included at the N-terminal. The resulting MEV construct demonstrated high structural quality and favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, and 5, followed by molecular dynamic simulations, suggested that the vaccine-receptor complexes are energetically feasible, stable, and robust. Immune simulation results showed that the MEV elicited significant responses, including IgG, IgM, CD8+ T-cells, CD4+ T-cells, and various cytokines (IFN-γ, TGF-β, IL-2, IL-10, and IL-12), along with a noticeable reduction in antigen levels. Despite these promising in-silico findings, further validation through preclinical and clinical trials is required to confirm the vaccine's efficacy and safety.

Efficacy of lipid nanoparticles-based vaccine to protect against vulvovaginal candidiasis (VVC): Implications for women's reproductive health.

Vulvovaginal candidiasis (VVC) is a common women's health issue, with rising antifungal resistance. This study was aimed to prepare and evaluate the efficacy of a lipid nanoparticle-based vaccine in a murine model of VVC. Dried and reconstituted vesicles containing C. albicans antigens (DRNPs-Ca-Ags) vaccine, formulated with phosphatidylcholine and cholesterol-based lipid nanoparticles via film hydration and freeze-drying. The safety evaluation of DRNPs-CaAgs was conducted by determining hepatic (AST, ALT) or renal (BUN, creatinine) biomarkers. Female mice were immunized with DRNPs-CaAgs or Alum-CaAgs, and immune responses were evaluated via antibody titers, IgG isotypes, and splenocyte proliferation. Protective efficacy of vaccine formulations was assessed through fungal burden, biofilm formation, cytokine levels, and histopathological analysis of vaginal tissues. Mice vaccinated with DRNPs-CaAgs showed significantly enhanced immune responses, with higher antibody titers and IgG2a levels as compared to the Alum-CaAgs group. Vaginal fungal burden was dramatically reduced (665±78 CFUs in DRNPs-CaAgs immunized group vs. 12,944±3540 CFUs in Alum-CaAgs group, p<0.01). Biofilm formation decreased by 45% (p<0.05), and inflammatory cytokines were significantly lowered. Histopathological analysis revealed minimal tissue damage in DRNPs-CaAgs vaccinated mice. The findings suggest DRNPs-CaAgs as a promising vaccine for VVC, eliciting strong immunity, reducing fungal load, and minimizing inflammation. While the reliance on a murine model is a limitation, future clinical trials are essential to evaluate its efficacy and safety in humans, offering a potential strategy to combat drug-resistant infections and improve women's reproductive health.

Influenza vaccine outcomes: a meta-analysis revealing morbidity benefits amid low infection prevention.

The morbidity and mortality associated with influenza viruses are a significant public health challenge. Annual vaccination against circulating influenza strains reduces hospitalisations and increases survival rates but requires a yearly redesign of vaccines against prevalent subtypes. The complex genetics of influenza viruses with high antigenic drift create an ongoing challenge in vaccine development to address dynamic influenza epidemiology. Understanding the evolution of influenza viruses and the vaccine's effectiveness against different types and subtypes is pivotal to designing public health measures against influenza. We conducted a systematic review and meta-analysis of 192 705 patients, collecting information on the incidence and severity of the disease. The results of this meta-analysis were further validated using data from 6 594 765 patients from TriNetX. We analysed the prevalence of the most common influenza A virus (IAV) subtypes (H1N1 and H3N2) and influenza B virus (IBV), as well as vaccination effectiveness against them in three age groups, given that age is associated with influenza disease severity. Our analysis reflects that overall vaccination against H1N1 IAV and IBV is effective in reducing infection and influenza-related complications in children aged <5 years old, individuals between 5 and 65 years old and older adults aged >65 years old. By contrast, while vaccination against H3N2 IAV is effective in protecting against infection in infants <5 years old, it provides reduced protection against infection in older individuals. Despite higher infection rates, vaccination against H3N2 remains as highly effective as vaccination against H1N1 and IBV in reducing influenza-related morbidity and mortality in all age groups. Detailing vaccine effectiveness in terms of infection protection and disease burden across different age groups is necessary for understanding vaccine impacts in terms of other outcomes, e.g. hospitalisations, mortality and disease severity; for improving vaccine formulations and public awareness; and for enhancing vaccination campaigns to improve coverage and public acceptance.

Risk of adverse events after Omicron XBB-adapted BNT162b2 COVID-19 vaccination in the United States.

Limited data exists regarding the safety of the COVID-19 2023-2024 vaccine formulations and whether the safety profiles differ from the original formulations. We evaluated the association between the BNT162b2 XBB COVID-19 vaccine and the risk of 20 pre-specified adverse events of special interest (AESIs). We identified commercially-insured individuals in the US age≥6months who received the BNT162b2 XBB COVID-19 vaccine between September 11, 2023 and January 15, 2024 within the Optum pre-adjudicated database. The self-controlled risk interval design was used to compare the incidence of 20 pre-specified AESIs during a risk period following vaccination to a control period. Relative incidence and 95% confidence intervals (CI) were estimated using exact conditional Poisson regression. The analysis included 113,459 individuals who received the BNT162b2 XBB COVID-19 vaccine (median [interquartile range] age: 47.1 [33.0-59.1] years). Relative incidence was calculated when ≥1 event occurred in either the risk or control period. For these 10 AESIs, there was no significant association between receipt of the BNT162b2 XBB COVID-19 vaccine and the incidence of any of these AESIs. Point estimates were higher in the risk period compared to the control period for ischemic stroke (relative incidence: 1.52; 95% CI: 0.44-5.94), myocarditis/pericarditis (relative incidence: 1.50; 95% CI: 0.22-12.61), immune-mediated myositis (relative incidence: 1.44; 95% CI: 0.83-2.52), herpes zoster (relative incidence: 1.24; 95% CI: 0.69-2.28), and non-febrile convulsions/seizures (relative incidence: 1.22; 95% CI: 0.86-1.73). These estimates were not statistically significant, though most were based on few events. Results were generally similar in subgroup analyses of individuals administered a concomitant seasonal influenza vaccine. There was no increased risk of 20 pre-specified AESIs following receipt of the BNT162b2 XBB COVID-19 vaccine among US commercially insured individuals aged ≥6months. Findings are consistent with the current evidence on the safety of BNT162b2 COVID-19 vaccines. Public registration: EUPAS108135.

SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development.

The COVID-19 pandemic, driven by the rapid evolution of the SARS-CoV-2 virus, presents ongoing challenges to global public health. SARS-CoV-2 is characterized by rapidly evolving mutations, especially in (but not limited to) the spike protein, complicating predictions about its evolutionary trajectory. These mutations have significantly affected transmissibility, immune evasion, and vaccine efficacy, leading to multiple pandemic waves with over half a billion cases and seven million deaths globally. Despite several strategies, from rapid vaccine development and administration to the design and availability of antivirals, including monoclonal antibodies, already having been employed, the persistent circulation of the virus and the emergence of new variants continue to result in high case numbers and fatalities. In the past four years, immense research efforts have contributed much to our understanding of the viral pathogenesis mechanism, the COVID-19 syndrome, and the host-microbe interactions, leading to the development of effective vaccines, diagnostic tools, and treatments. The focus of this review is to provide a comprehensive analysis of the functional impact of mutations on diagnosis, treatments, and vaccine effectiveness. We further discuss vaccine safety in pregnancy and the implications of hybrid immunity on long-term protection against infection, as well as the latest developments on a pan-coronavirus vaccine and nasal formulations, emphasizing the need for continued surveillance, research, and adaptive public health strategies in response to the ongoing SARS-CoV-2 evolution race.

Dual-Engineered Phage Vaccine Platform Facilitates STING Activation for Influenza Protection.

Influenza epidemics remain a global public health challenge. Vaccination with nucleic acid-based vaccines, which trigger strong cellular and humoral immune responses, represents a promising approach for preventing virus infection. However, its effectiveness relies on efficient delivery and an immunoadjuvant. Here, we constructed a gene- and nanoengineered vaccine delivery platform via modifying MnO2 nanoparticles (NPs) onto the surface of the M13 phage, which carried the hemagglutinin stem gene of influenza A virus preceded by a eukaryotic initial transcriptional region. Specifically, the M13 phage protected the inserted nucleic acid vaccine against degradation due to the existence of capsid proteins. MnO2 NPs released Mn2+ ions under the acidic condition of endolysosomes, thereby promoting the cytoplasmic delivery of phage vaccines, which significantly improved the antigen expression. Moreover, Mn2+ acted as a potent adjuvant for dendritic cell maturation by activating the cGAS/STING pathway. Immunization with the engineered phage vaccine induced CD4+ T cell, CD8+ T cell, and humoral immune responses in mice. In infected mouse models, the vaccines ameliorated weight loss, survival rate, lung virus titers, and pulmonary pathologies and conferred full protection against influenza viruses. Collectively, we developed a dual-engineered phage vaccine platform, offering an alternative regimen for optimizing nucleic acid vaccines, which may have broad applications in the rational design of vaccine formulations.

Recombinant VSV as a platform for rabies vaccine development: Enhancing immunogenicity and safety

The research investigates the possibility of development of a recombinant vesicular stomatitis virus (VSV) expressing the rabies virus glycoprotein as a novel rabies vaccine. The recombinant VSV can show robust immunogenicity, eliciting strong virus-neutralizing antibody responses in both mice and dogs. The oral vaccine formulation proved stable in simulated gastric conditions and induced immune responses comparable to intramuscular injection. Long-term immunity studies indicated high antibody levels and protection against rabies virus challenge at six months and one-year post-immunization, suggesting potential for durable immunity, particularly in dogs. Toxicity studies can be used to analyze adverse effects, confirming the vaccine’s safety. The potential for the recombinant VSV vaccine to induce mucosal immunity and spread through social behaviours in wildlife populations presents a promising approach for rabies control. However, challenges such as ensuring genetic stability and evaluating environmental impacts must be addressed. This research highlights the recombinant VSV-based vaccine’s promise as an effective, safe, and potentially self-disseminating tool for rabies prevention, with implications for both human and veterinary applications.