Vaccine Efficacy Research Articles

Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates

The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences. Thus, the induction of immune responses against the V2 epitope, which had exceptional identity between the vaccine and challenge Env strains, may have contributed to the high protection in primates.

B cell αv integrin regulates germinal center derived lung-resident IgA B cell responses following influenza virus infection.

Emerging studies have highlighted the importance of tissue-resident B cells in the lungs, for protective immunity against respiratory viruses. However, the mechanisms controlling generation and maintenance of such tissue-resident B cells at respiratory sites remain obscure. We have previously shown that αv integrins limit B cell responses to antigens containing Toll-like receptor ligands, and that deletion of B cell αv integrins, in mice, enhances germinal center (GC)-derived long-lived B cell responses after systemic immunization with viral antigens. Here we investigated whether αv also regulates B cell responses at the respiratory tract during viral infection. Our data show that αv integrin restricts tissue-resident B cell responses in the airway, and that deletion of B cell αv promotes generation of lung-resident IgA B cell responses following influenza A virus (IAV) infection. Investigating the mechanism for this, we found that loss of B cell αv, promotes persistence of GC reactions locally in the lungs, which leads to increases in lung-resident IgA+ memory B cells, cross-reactive to antigenic variants. Thus, these studies reveal how IgA B cells are maintained in the lungs and point to a new strategy to improve the durability of lung-resident IgA B cell responses for IAV vaccine efficacy.

Efficacy-focused and autonomy-supportive messaging in social media vaccine campaigns: insights from a Facebook split test

ABSTRACT Background In the context of social media vaccine campaigns, understanding the impact of message framing on audience engagement is crucial. This study examines the efficacy of messages centered on efficacy versus autonomy, informed by theoretical frameworks: the Extended Parallel Process Model (EPPM) and Self Determination Theory (SDT). Methods Utilizing the Facebook A/B Split Test (FBST) feature, an online experiment was conducted to compare the response to two different messages: one emphasizing vaccine efficacy (EPPM-informed) and the other focusing on individual autonomy in making vaccine decisions (SDT-informed). The primary measure of interest was the number of clicks on a link directing to a pro-vaccine website. Results The findings indicated that the autonomy-centered (SDT-informed) message resulted in a significantly higher click-through rate to the pro-vaccine website, particularly among users aged 65 and above. Furthermore, analysis of comments from Facebook users identified factors potentially contributing to vaccine hesitancy, with mistrust being the most dominant. Conclusions The study underscores the importance of tailoring social media vaccine campaigns to address the autonomy needs of the target audience while considering trust-related issues to mitigate vaccine hesitancy. Emphasizing individual autonomy in vaccine decision-making processes can enhance engagement with pro-vaccine content, especially in older demographics.

Tyrosinase-Mediated Conjugation for Antigen Display on Ferritin Nanoparticles.

Ferritin (Ft) nanoparticles have become versatile platforms for displaying antigens, being a promising technology for vaccine development. While genetic fusion has traditionally been the preferred method for antigen display, concerns about improper folding and steric hindrance that may compromise vaccine efficacy or stability have prompted alternative approaches. Bioconjugation offers the advantage of preserving native protein structure and function, with recent advancements improving efficiency and specificity. In this study, we used tyrosinase (TYR) to bioconjugate the receptor binding domain of the SARS-CoV-2 spike protein, tagged with a tyrosine (RBD-Y), to native cysteines on Ft, resulting in RBD-Y-Ft nanoparticles. We quantified available cysteines on ferritin using Ellman's assay and monitored their reduction during the reactions. Denaturing analytics (via SDS-PAGE, Western blot, and LC-TOF-MS) confirmed the formation of RBD-Y-Ft monomers with an expected molecular weight of 46 kDa. Mass photometry and HPLC estimated a molecular weight of RBD-Y-Ft nanoparticles of 680 kDa, which was higher than that of nonfunctionalized ferritin (480 kDa), indicating successful binding of up to eight RBD-Y antigens per 24-mer Ft nanoparticle. This work enhances our understanding of how Ft nanoparticles can be engineered to present antigens, leveraging them as a robust scaffold for producing tailored-made candidate vaccines in a timely manner.

N-protein vaccine is effective against COVID-19: Phase 3, randomized, double-blind, placebo-controlled clinical trial

Despite the success of first-generation COVID-19 vaccines targeting the spike (S) protein, emerging SARS-CoV-2 variants have led to immune escape, reducing the efficacy of these vaccines. Additionally, some individuals are unable to mount an effective immune response to S protein-based vaccines. This has created a need for alternative vaccine strategies that are less susceptible to mutations and capable of providing broad and durable protection. This study aimed to evaluate the efficacy and safety of a novel COVID-19 vaccine based on the full-length recombinant nucleocapsid (N) protein of SARS-CoV-2. We conducted a prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT05726084) in Russia. Participants (n=5229) were adults aged 18 years and older, with a BMI of 18.5-30kg/m², and without significant clinical abnormalities. They were randomized in a 2:1 ratio to receive a single intramuscular dose of either the N protein-based vaccine (50µg) or placebo. Randomization was done through block randomization, and masking was ensured by providing visually identical formulations of vaccine and placebo. The primary outcome was the incidence of symptomatic COVID-19 confirmed by PCR more than 15 days after vaccination within a 180-day observation period, analyzed on an intention-to-treat basis. Between May 18, 2023, and August 9, 2023, 5229 participants were randomized, with 3486 receiving the vaccine and 1743 receiving the placebo. Eight cases of PCR-confirmed symptomatic COVID-19 occurred in the vaccine group (0.23%) compared to 27 cases in the placebo group (1.55%), yielding a vaccine efficacy of 85.2% (95% CI: 67.4-93.3; p<0.0001). Adverse events were mostly mild and included local injection site reactions. There were no vaccine-related serious adverse events. The N protein-based COVID-19 vaccine demonstrated significant efficacy and a favorable safety profile, suggesting it could be a valuable addition to the global vaccination effort, particularly in addressing immune escape variants and offering an alternative for those unable to respond to S protein-based vaccines. These results support the continued development and potential deployment of N protein-based vaccines in the ongoing fight against COVID-19.

Efficacy of anti-RSV vaccination in preventing respiratory syncytial virus disease and severe illness in older adults: a systematic review of randomized controlled trials.

Several vaccines against respiratory syncytial virus (RSV) are being developed. The objective of this systematic review is to determine the efficacy of these vaccines in preventing RSV disease in adults over 60years of age, especially regarding severe illness. We researched MEDLINE, CENTRAL, Scopus, medRxiv, bioRxiv and ClinicalTrials.gov until April/2024. Randomized controlled trials studying an anti-RSV vaccine in adults above 60years and reporting RSV-related acute respiratory infection/disease (ARI/ARD), lower respiratory tract infection/disease (LRTI/LRTD) and severe LRTI/LRTD were included. Vaccine efficacy was calculated as ([1-risk ratio] × 100). Risk of bias and certainty of evidence were assessed by RoB2 tool and GRADE approach. The meta-analytical relative risk of ARI/ARD and LRTI/LRTD was estimated, with a subgroup analysis performed according to the vaccine type. The random effects model was used. We included seven studies, five addressing prefusion vaccines and two regarding non-prefusion ones. The number of RSV-related LRTI/LRTD cases was reduced by vaccination, with a relative risk of 0.39 [CI 95% 0.22 to 0.69] and a vaccine efficacy of 61%. Considering the subgroup of prefusion vaccines alone, there is a relative risk of 0.27 [CI 95% 0.19 to 0.36] for LRTI/LRTD and a vaccine efficacy of 73%. ARI/ARD incidence presented a similar pattern. Only one trial reports results for severe LRTI/LRTD, with a vaccine efficacy of 94.1% [95% CI 62.4 to 99.9]. Prefusion anti-RSV vaccines are efficacious in the prevention of LTRI/LTRD and ARI/ARD cases. More studies regarding severe LTRI/LTRD are necessary in the future.

Vaccines efficacy against infection with circulating feline calicivirus after one single injection: Comparison of Leucofeligen™ FeLV/RCP and Purevax™ RCPFeLV vaccines

Feline calicivirus (FCV) is a worldwide pathogen that affects the general health status of cats. The aim of this study was to assess the efficacy of the FCV component of two multivalent commercial vaccines after one injection. The cats assigned to the vaccinated groups received one subcutaneous injection of either the Leucofeligen™ FeLV/RCP (Virbac, France) vaccine or the Purevax™ RCPFeLV (Boehringer Ingelheim, Germany) vaccine. In the control group, the cats did not receive any vaccine. Three weeks after the vaccine injection, all the cats were inoculated with a heterologous calicivirus strain, isolated in the field. The clinical signs of calicivirosis and the viral shedding were assessed. The results demonstrated that Leucofeligen™ FeLV/RCP could protect kittens against FCV infection by reducing clinical signs and viral excretion from 3 weeks after the first injection of primary vaccination, whereas Purevax™ RCPFeLV couldn't offer the same level of protection in similar experimental conditions.

Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice

ABSTRACT Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO4 as an adjuvant. The AH vaccine was constructed by fusing Als317-432 and Hyr125-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO4, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine’s efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO4 combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO4 vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.

Immunity and Protective Efficacy of a Plant-Based Tobacco Mosaic Virus-like Nanoparticle Vaccine against Influenza a Virus in Mice.

The rapid production of influenza vaccines is crucial to meet increasing pandemic response demands. Here, we developed plant-made vaccines comprising centralized consensus influenza hemagglutinin (HA-con) proteins (H1 and H3 subtypes) conjugated to a modified plant virus, tobacco mosaic virus (TMV) nanoparticle (TMV-HA-con). We compared immune responses and protective efficacy against historical H1 or H3 influenza A virus infections among TMV-HA-con, HA-con protein combined with AddaVax™ adjuvant, and whole-inactivated virus vaccine (Fluzone®). Immunogenicity studies demonstrated robust IgG, IgM, and IgA responses in the TMV-HA-con and HA-con protein vaccinated groups, with relatively low induction of interferon (IFN)-γ+ T-cell responses across all vaccinated groups. The TMV-HA-con and HA-con protein groups displayed partial protection (100% and 80% survival) with minimal weight loss following challenge with two H1N1 strains. The HA-con protein group exhibited 80% and 100% survival against two H3 strains, whereas the TMV-HA-con groups showed reduced protection (20% survival). The Fluzone® group conferred 20-100% survival against two H1N1 strains and one H3N1 strain, but did not protect against H3N2 infection. Our findings indicate that TMV-HA and HA-con protein vaccines with adjuvant induce protective immune responses against influenza A virus infections. Furthermore, our results underscore the potential of plant-based production using TMV-like nanoparticles for developing influenza A virus candidate vaccines.

Enhancing vaccine efficacy: Evaluating the superiority of cationic liposome-embedded squalene adjuvant against PCV2 infection

Cationic liposome-embedded squalene (CLS) is a promising adjuvant that enhances antigen stability and mobility and improves immune response. This study compares the efficacy of a CLS-adjuvant porcine circovirus type 2 (PCV2) vaccine (CSV) with a conventional vaccine against PCV2. The CSV vaccine showed superior stability and was effective against PCV2-induced growth decline. It significantly increased serum immunoglobulin and cytokine levels, reduced serum PCV2 DNA, shortened the duration of viremia, and provided robust protection. CSV outperformed conventional vaccines, highlighting its potential for innovative vaccine development.

Codon optimized influenza H1 HA sequence but not CTLA-4 targeting of HA antigen to enhance the efficacy of DNA vaccines in an animal model

Infections caused by the influenza virus lead to both epidemic and pandemic outbreaks in humans and animals. Owing to their rapid production, safety, and stability, DNA vaccines represent a promising avenue for eliciting immunity and thwarting viral infections. While DNA vaccines have demonstrated substantial efficacy in murine models, their effectiveness in larger animals remains subdued. This limitation may be addressed by augmenting the immunogenicity of DNA-based vaccines. In the investigation here, protein expression was enhanced via codon optimization and then mouse cytotoxic T-lymphocyte antigen 4 (CTLA-4) was harnessed as a modulatory adjunct to bind directly to antigen-presenting cells. Further, the study evaluated the immunogenicity of two variants of the hemagglutinin (HA) antigen, i.e. the full-length and the C-terminal deletion versions. The study findings revealed that the codon-optimized HA gene (pcHA) led to increased protein synthesis, as evidenced by elevated mRNA levels. Codon optimization also significantly bolstered both cellular and humoral immune responses. In cytokine assays, all plasmid constructs, particularly pCTLA4-cHA, induced robust interferon (IFN)-γ production, while interleukin (IL)-4 levels remained uniformly non-significant. Mice immunized with pcHA displayed an augmented presence of IFNγ+ T-cells, underscoring the enhanced potency of the codon-optimized HA vaccine. Contrarily, CTLA-4-fused DNA vaccines did not significantly amplify the immune response.

Comparison of post-COVID-19 pulmonary complications in individuals vaccinated with BioNTech or Sinovac

Aims: Although several research have been undertaken to investigate the impact of the vaccination on long Coronavirus Disease 2019 (COVID-19) syndrome or post-acute sequelae, there is a lack of published evidence on the long-term effects of vaccines on lung-sequelae-related disease. Considering the limited global COVID-19 vaccine distribution, it is essential to establish the impact of vaccination in reducing pulmonary complications. Turkey has been offering COVID-19 vaccines from two platforms, including BNT162b2 (Pfizer-BioNTech, mRNA vaccine) and CoronaVac (Sinovac, inactivated vaccine). This study aimed to evaluate the efficacy of BioNTech and Sinovac vaccines in reducing post-COVID-19 pulmonary complications in individuals. Methods: A total of 94 patients COVID-19 pneumonia patients who were categorized based on the quantity of BioNTech or Sinovac vaccines they received before their first COVID-19 infection were included. The inclusion criteria consisted of a confirmed diagnosis of COVID-19 pneumonia through polymerase chain reaction testing, availability of the mentioned before and follow-up computed tomography scans, and administration of at least one dose of vaccine. Results: The number of complications in patients fully vaccinated with Sinovac and who experienced post-COVID lung complications was significantly greater than in those vaccinated with BioNTech. The C-reactive protein and D-Dimer measurements of individuals who experienced complications in the Sinovac vaccinated group were significantly elevated on the index date. Conclusion: The quantity of lung sequelae after COVID and laboratory parameters indicating this result were found to be higher in inactivated virus vaccines than in mRNA vaccines. This suggests that the protection of inactivated vaccines may be insufficient in severe cases.

Navigating the Landscape of B Cell Mediated Immunity and Antibody Monitoring in SARS-CoV-2 Vaccine Efficacy: Tools, Strategies and Clinical Trial Insights

Correlates of Protection (CoP) are biomarkers above a defined threshold that can replace clinical outcomes as primary endpoints, predicting vaccine effectiveness to support the approval of new vaccines or follow up studies. In the context of COVID-19 vaccination, CoPs can help address challenges such as demonstrating vaccine effectiveness in special populations, against emerging SARS-CoV-2 variants or determining the durability of vaccine-elicited immunity. While anti-spike IgG titres and viral neutralising capacity have been characterised as CoPs for COVID-19 vaccination, the contribution of other components of the humoral immune response to immediate and long-term protective immunity is less well characterised. This review examines the evidence supporting the use of CoPs in COVID-19 clinical vaccine trials, and how they can be used to define a protective threshold of immunity. It also highlights alternative humoral immune biomarkers, including Fc effector function, mucosal immunity, and the generation of long-lived plasma and memory B cells and discuss how these can be applied to clinical studies and the tools available to study them.

Development and Assessment of the Performance of a Novel Parabolic Trough Solar Collector-Driven Three-Stage Cooling Cycle

Abstract A gaseous flow is employed as heat transfer fluid (HTF) in a parabolic trough solar collector (PTSC) for simultaneous production of cooling at three different levels of temperature to meet the demands of air conditioning, refrigeration, and ultra-low-temperature refrigeration required to ensure the efficacy of some special vaccines. The combined system consists of five subsystems including PTSC, Kalina cycle (KC), ejector refrigeration cycle (ERC), cascaded refrigeration cycle (CRC), and absorption refrigeration cycle (ARC). A simulation through an engineering equation solver (EES) is conducted to assess the impact of internal tube diameter of absorber and solar irradiation on rise of HTF temperature and mass flowrate of Kalina cycle fluid. It is determined that for given solar irradiation, the temperature of HTF goes down when internal diameter of absorber tube is enlarged. The influence of weather conditions; solar irradiation and ambient temperature, type of HTF, and concentration of ammonia–water basic solution on thermal and exergy efficiencies of three-stage cooling cycle (TSC) are examined. The TSC with helium-operated PTSC delivers better results than air and CO2. Exergy analysis shows that solar collector (30.26%) dissipates the highest exergy, followed by the ejector (12.5%) and vapor generator subsystem (7.61%). The type of CRC fluid pair affects TSC cycle refrigeration capacity and cooling exergy efficiency. The promotion of solar irradiation from 850 to 1200 W/m2 increases the cooling exergy efficiency of the three-stage cycle from 6.72% to 9.52% when the evaporator temperature is set at −45 °C and CRC employs NH3-propylene.

Identifying Plasmodium P36 and P52 antigens for co-administration with circumsporozoite protein to enhance vaccine efficacy.

Vaccines targeting the complex pre-erythrocytic stage of Plasmodium parasites may benefit from inclusion of multiple antigens. However, discerning protective effects can be difficult because newer candidates may not be as protective as leading antigens like the circumsporozoite protein (CSP) in the conventional pre-clinical mouse model. We developed a modified mouse model challenge strategy that maximizes the contribution of T cells induced by novel candidate antigens at the sporozoite challenge time point and used this approach to test Plasmodium P36 and P52 vaccine candidates alone and in concert with non-protective doses of CSP. Co-administration of P36 and/or P52 with CSP achieved 80-100% sterile protection in mice, compared to only 7-30% protection for each individual antigen. P36 and P52 vaccination induced murine CD4+ and CD8+ T cell responses, but not antibody responses. This study adds P36 and P52 as promising vaccine antigens that may enhance protection achieved by CSP vaccination.

A vaccination-based COVID-19 model: Analysis and prediction using Hamiltonian Monte Carlo

Compartmental models have emerged as robust computational frameworks and have yielded remarkable success in the fight against COVID-19. This study proposes a vaccination-based compartmental model for COVID-19 transmission dynamics. The model reflects the specific stages of COVID-19 infection and integrates a vaccination strategy, allowing for a comprehensive analysis of how vaccination rates influence the disease spread. We fit this model to daily confirmed COVID-19 cases in Tennessee, United States of America (USA), from June 4 to November 26, 2021, in a Bayesian inference approach using the Hamiltonian Monte Carlo (HMC) algorithm. First, excluding vaccination dynamics from the model, we estimated key epidemiological parameters like infection, recovery, and disease-induced death rates. This analysis yielded a basic reproduction number (R0) of 1.5. Second, we incorporated vaccination dynamics and estimated the vaccination rate for three vaccines: 0.0051 per day for both Pfizer and Moderna and 0.0059 per day for Janssen. The fitted curves show reductions in the epidemic peak for all three vaccines. Pfizer and Moderna vaccines bring the peak down from 8,029 infected cases to 5,616 infected cases, while the Janssen vaccine reduces it, to 6,493 infected cases. Simulations of the model by varying the vaccination rate and vaccine efficacy were performed. A highly effective vaccine (95% efficacy) with a daily vaccination rate of 0.006 halved COVID-19 infections, reducing cases from 8,029 to around 4,000. The results also show that the model's prediction accuracy for new observations improves with the number of observed data used to train the model.

Differences in PCV13 Recommendation Practices between Pediatric Care Providers and Primary Care Providers in China: A Cross-Sectional Survey of Behavior and Social Drivers.

Objectives: This study examines the recommendation behaviors and influencing factors for the 13-valent Pneumococcal Conjugate Vaccine (PCV13) among 3579 Chinese healthcare workers (HCWs), including 1775 pediatric care providers (Peds-PCPs) and 1804 primary care providers (PCPs). Data were collected from May to July 2023 through a national cross-sectional survey using a structured questionnaire, distributed across hospitals providing pediatric services in five provincial-level administrative divisions. Methods: The sociodemographic data, vaccine knowledge, and recommendation practices were analyzed using Pearson's chi-square test, Wilcoxson rank-sum test, and multivariate logistic regression. Results show that while PCPs are more likely to recommend PCV13, vaccine hesitancy persists among Peds-PCPs. Logistic regression revealed that higher influenza vaccination intention, salary, vaccine consultation frequency, familiarity with immunization, work ethic, and flexible schedules positively impacted HCWs' recommendation behavior. Results: Factors influencing Peds-PCPs' recommendations include vaccine training (OR: 1.470, CI: 1.049-2.509), safety recognition (OR: 1.986, CI: 1.163-3.391), concern over rejection (OR = 1.274, CI: 1.076-1.508) and vaccine cost (OR = 1.203, CI: 1.023-1.414). For PCPs, influencing factors were the perceived susceptibility of children to pneumonia (OR = 2.185, CI: 1.074-4.445), acceptance of herd immunity (OR: 1.717, CI: 1.101-2.677), and belief that parents with better family conditions are more likely to accept vaccine recommendations (OR = 1.229, CI: 1.024-1.477). Conclusion: This survey underscores the need for tailored interventions to address differing perceptions and enhance confidence in the safety and efficacy of vaccines among HCWs, particularly Peds-PCPs.

Comprehensive Spatial-Temporal and Risk Factor Insights for Optimizing Livestock Anthrax Vaccination Strategies in Karnataka, India.

Anthrax, a zoonotic disease affecting both livestock and humans globally, is caused by Bacillus anthracis. The objectives of this study were the following: (1) to identify environmental risk factors for anthrax and use this information to develop an improved predictive risk map, and (2) to estimate spatial variation in basic reproduction number (Ro) and herd immunity threshold at the village level, which can be used to optimize vaccination policies within high-risk regions. Based on the anthrax incidences from 2000-2023 and vaccine administration figures between 2008 and 2022 in Karnataka, this study depicted spatiotemporal pattern analysis to derive a risk map employing machine learning algorithms and estimate Ro and herd immunity threshold for better vaccination coverage. Risk factors considered were key meteorological, remote sensing, soil, and geographical parameters. Spatial autocorrelation and SaTScan analysis revealed the presence of hotspots and clusters predominantly in the southern, central, and uppermost northern districts of Karnataka and temporal cluster distribution between June and September. Factors significantly associated with anthrax were air temperature, surface pressure, land surface temperature (LST), enhanced vegetation index (EVI), potential evapotranspiration (PET), soil temperature, soil moisture, pH, available potassium, sulphur, and boron, elevation, and proximity to waterbodies and waterways. Ensemble technique with random forest and classification tree models were used to improve the prediction accuracy of anthrax. High-risk areas are expected in villages in the southern, central, and extreme northern districts of Karnataka. The estimated Ro revealed 11 high-risk districts with Ro > 1.50 and respective herd immunity thresholds ranging from 11.24% to 55.47%, and the assessment of vaccination coverage at the 70%, 80%, and 90% vaccine efficacy levels, all serving for need-based strategic vaccine allocation. A comparison analysis of vaccinations administered and vaccination coverage estimated in this study is used to illustrate difference in the supply and vaccine force. The findings from the present study may support in planning preventive interventions, resource allocation, especially of vaccines, and other control strategies against anthrax across Karnataka, specifically focusing on predicted high-risk regions.

From ancient remedies to modern miracles: tracing the evolution of vaccines and their impact on public health.

This review traces the development of vaccines from ancient times to the present, highlighting major milestones and challenges. It covers the significant impact of vaccines on public health, including the eradication of diseases such as smallpox and the reduction of others such as polio, measles, and influenza. The review provides an in-depth look at the COVID-19 vaccines, which were developed at unprecedented speeds due to the urgent global need. The study emphasizes the ongoing potential of vaccine development to address future global health challenges, demonstrating the critical role vaccines play in disease prevention and public health. Moreover, it discusses the evolution of vaccine technology, from live-attenuated and inactivated vaccines to modern recombinant and mRNA vaccines, showcasing the advancements that have enabled rapid responses to emerging infectious diseases. The review underscores the importance of continued investment in research and development, global collaboration, and the adoption of new technologies to enhance vaccine efficacy and coverage. By exploring historical and contemporary examples, the article illustrates how vaccines have transformed medical practice and public health outcomes, providing valuable insights into future directions for vaccine innovation and deployment.

A Quadruple Gene-Deleted Live BoHV-1 Subunit RVFV Vaccine Vector Reactivates from Latency and Replicates in the TG Neurons of Calves but Is Not Transported to and Shed from Nasal Mucosa.

Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV.