Immunogenicity Of Vaccine Research Articles

Astragalus Polysaccharide improves immunogenicity of influenza vaccine as well as modulate gut microbiota in BALB/c mice

BackgroundVaccination is the best way to prevent influenza virus infection, and insufficient antibodies make it difficult to resist influenza virus invasion. Astragalus Polysaccharide (APS) has a boosting effect on immunity, so we evaluate the effect of APS as an immune adjuvant for H1N1 influenza vaccines in this study. MethodsThe mice were immunized twice with influenza A (H1N1) vaccine and APS. Subsequently, the serum antibody levels were assessed using enzyme-linked immunosorbent assay (ELISA). The frequency of peripheral immune T cells was determined by flow cytometry. Following this, the immunized mice were exposed to a lethal dose of the virus, and changes in body weight and survival rates were recorded. Hematoxylin-eosin staining was employed to observe pathological alterations in lung and intestinal tissues. Western blot analysis was conducted to detect the expression of intestinal barrier function proteins (Occludin and Claudin-1). ELISA was utilized to measure the expression level of serum inflammatory cytokine TNF-α. Fresh mouse feces were collected after the initial immunization as well as after viral infection for 16S rRNA analysis aimed at detecting alterations in gut microbiota. ResultsCompared to the Hemagglutinin (HA) group, the APS group demonstrated higher levels of immunoglobulin G (IgG), IgG1, and IgG3, as well as neutralizing antibody levels. Additionally, it increased the frequency of CD8+ cells to enhance resistance against lethal infection. On day 14 post-infection, the high-dose APS group exhibited a higher survival rate (71.40 %) compared to the HA group (14.28 %), along with faster weight recovery. Furthermore, APS was found to ameliorate alveolar damage in lung tissue and rectify intestinal structural disorder. It also upregulated the expression levels of tight junction proteins Occludin and Claudin-1 in intestinal tissue while reducing serum TNF-α expression levels. In addition, populations of Colidextribacter, Peptococcaceae, and Ruminococcaceae were the dominant gut microbiota in the APS group after viral infection. ConclusionAPS has an immune-enhancing effect and is expected to be a novel adjuvant in the H1N1 influenza vaccine.

Antibody Fc receptor binding and T cell responses to homologous and heterologous immunization with inactivated or mRNA vaccines against SARS-CoV-2

Whole virion inactivated vaccine CoronaVac (C) and Spike (S) mRNA BNT162b2 (B) vaccines differ greatly in their ability to elicit neutralizing antibodies but have somewhat comparable effectiveness in protecting from severe COVID-19. We conducted further analyses for a randomized trial (Cobovax study, NCT05057169) of third dose homologous and heterologous booster vaccination, i.e. four interventions CC-C, CC-B, BB-C and BB-B. Here, we assess vaccine immunogenicity beyond neutralizing function, including S and non-S antibodies with Fc receptor (FcR) binding, antibody avidity and T cell specificity to 6 months post-vaccination. Ancestral and Omicron S-specific IgG and FcR binding are significantly higher by BNT162b2 booster than CoronaVac, regardless of first doses. Nucleocapsid (N) antibodies are only increased in homologous boosted CoronaVac participants (CC-C). CoronaVac primed participants have lower baseline S-specific CD4+ IFNγ+ cells, but are significantly increased by either CoronaVac or BNT162b2 boosters. Priming vaccine content defined T cell peptide specificity preference, with S-specific T cells dominating B primed groups and non-S structural peptides contributing more in C primed groups, regardless of booster type. S-specific CD4+ T cell responses, N-specific antibodies, and antibody effector functions via Fc receptor binding may contribute to protection and compensate for less potent neutralizing responses in CoronaVac recipients.

The use of controlled human infection models to identify correlates of protection for invasive Salmonella vaccines.

Controlled human infection model (CHIM) studies, which involve deliberate exposure of healthy human volunteers to an infectious agent, are recognised as important tools to advance vaccine development. These studies not only facilitate estimates of vaccine efficacy, but also offer an experimental approach to study disease pathogenesis and profile vaccine immunogenicity in a controlled environment, allowing correlation with clinical outcomes. Consequently, the data from CHIMs can be used to identify immunological correlates of protection (CoP), which can help accelerate vaccine development. In the case of invasive Salmonella infections, vaccination offers a potential instrument to prevent disease. Invasive Salmonella disease, caused by the enteric fever pathogens Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi A, B and C, and nontyphoidal Salmonella (iNTS), remains a significant cause of mortality and morbidity in low- and middle-income countries, resulting in over 200,000 deaths and the loss of 15 million DALYs annually. CHIM studies have contributed to the understanding of S. Typhi infection and provided invaluable insight into the development of vaccines and CoP following vaccination against S. Typhi. However, CoP are less well understood for S. Paratyphi A and iNTS. This brief review focuses on the contribution of vaccine-CHIM trials to our understanding of the immune mechanisms associated with protection following vaccines against invasive Salmonella pathogens, particularly in relation to CoP.

Design, Immunogenicity and Preclinical Efficacy of the ChAdOx1.COVconsv12 Pan-Sarbecovirus T-Cell Vaccine.

During the COVID-19 pandemic, antibody-based vaccines targeting the SARS-CoV-2 spike glycoprotein were the focus for development because neutralizing antibodies were associated with protection against the SARS-CoV-2 infection pre-clinically and in humans. While deploying these spike-based vaccines saved millions of lives worldwide, it has become clear that the immunological mechanisms of protection against severe disease are multifaceted and involve non-neutralizing antibody components. Here, we describe a novel pan-sarbecovirus T-cell vaccine, ChAdOx1.COVconsv12, designed to complement and broaden the protection of spike vaccines. The vaccine immunogen COVconsv12 employs the two regions in the viral proteome most conserved among sarbecoviruses, which are delivered by replication-deficient vector ChAdOx1. It directs T cells towards epitopes shared among sarbecoviruses including evolving SARS-CoV-2 variants. Here, we show that ChAdOx1.COVconsv12 induced broad T-cell responses in the BALB/c and C57BL/6 mice. In the Syrian hamster challenge model, ChAdOx1.COVconsv12 alone did not protect against the SARS-CoV-2 infection, but when co-administered with 1/50th of the ChAdOx1 nCoV-19 spike vaccine protective dose, faster recovery and lower oral swab viral load were observed. Induction of CD8+ T cells may decrease COVID-19 severity and extend the T-cell response coverage of variants to match the known (and as yet unknown) members of the β-coronavirus family.

Codon optimization of voraxin α sequence enhances the immunogenicity of a recombinant vaccine against Hyalomma anatolicum infestation in rabbits

Research has shown that voraxin α derived from male ticks stimulates blood feeding to engorge in female ticks. Whereas, the oviposition rate, egg weight, and body weight of female ticks were reduced in animals vaccinated with recombinant (r-) voraxin α. These data suggest a potential role of r-voraxin α as a functional anti-tick antigen in Rhipicephalus appendiculatus and Amblyomma hebraeum tick infestation. This study investigated the immunogenicity of r-voraxin α protein from Hyalomma anatolicum (H. anatolicum) tick as an anti-tick vaccine in rabbits. The H. anatolicum voraxin α sequence was optimized according to the codon usage in E. coli before being sub-cloned into pQE30. The gene sequence of the voraxin α was synthesized, verified by DNA sequencing, cloned in a pQE30 vector, and transformed into E. coli. Then, the expression of the r-voraxin α protein was confirmed by SDS-PAGE and Western blot analysis. Subsequently, three rabbits were immunized with the r-voraxin α as the vaccinated group, whereas three rabbits without injection were considered the control group. The result indicated the success of cloning of codon-optimized H. anatolicum voraxin α gene. Moreover, the expression of the r-voraxin α protein (approximately 18 kDa) in the bacterial expression system was confirmed by SDS-PAGE and Western blot analysis. The results of this study showed that the mortality rate in vaccine recipients increased compared to the control group (P < 0.01). Also, the egg weight, oviposition rate, and engorgement weight of female ticks fed from vaccinated animals were significantly reduced compared to the control group (P < 0.01). The results confirmed that the codon-optimized H. anatolicum voraxin α gene expressed in the bacterial expression system could be a suitable anti-tick vaccine against H. anatolicum tick infestation.

Safety and Immunogenicity of Trivalent Oral Polio Vaccine in Vaccinated Children and Vaccine-Naïve Infants: A Phase 4 Study.

In the context of polio eradication, novel oral polio vaccines for type 2 (nOPV2) were developed, and types 1 and 3 polioviruses are being developed. We aimed to generate trivalent oral poliovirus vaccine (tOPV) safety and immunogenicity data as a reference for comparing with novel OPV formulations. This was a single-center, open-label, phase 4 study in March 2016 in the Dominican Republic with healthy children previously vaccinated with ≥3 doses of tOPV receiving one dose of tOPV and vaccine-naïve infants receiving 3 doses of tOPV. Safety and immunogenicity were assessed. No serious adverse reactions or important medical reactions were reported. Seroconversion (SC) rates at Day 28 in children were 32.7%, 36.7%, and 46.9% for types 1, 2, and 3, respectively, and seroprotection (SP) rates 28 days after one dose increased from 89.8% at baseline to 93.9%, 98.0% to 100%, and 83.7% to 98.0% for types 1, 2, and 3, respectively. In infants, SC rates were 88.5%, 98.1%, and 96.2% for types 1, 2, and 3, respectively. SP rates at Day 84 were 93.3%, 100%, and 96.2% for types 1, 2, and 3, respectively. This information can be used as a reference to compare with novel monovalent or trivalent OPVs under development.

Immunogenicity and Protective Efficacy of Dose-Sparing Epigraph Vaccine against H3 Swine Influenza A Virus.

Swine influenza A virus (IAV-S) is a highly prevalent and transmissible pathogen infecting worldwide swine populations. Our previous work has shown that the computationally derived vaccine platform, Epigraph, can induce broadly cross-reactive and durable immunity against H3 IAV-S in mice and swine. Therefore, in this study, we assess the immunogenicity and protective efficacy of the Epigraph vaccine at increasingly lower doses to determine the minimum dose required to maintain protective immunity against three genetically divergent H3 IAV-S. We assessed both antibody and T cell responses and then challenged with three H3N2 IAV-S derived from either Cluster IV(A), Cluster I, or the 2010.1 "human-like" cluster and assessed protection through reduced pathology, reduced viral load in the lungs, and reduced viral shedding from nasal swabs. Overall, we observed a dose-dependent effect where the highest dose of Epigraph protected against all three challenges, the middle dose of Epigraph protected against more genetically similar IAV-S, and the lowest dose of Epigraph only protected against genetically similar IAV-S. The results of these studies can be used to continue developing a broadly protective and low-dose vaccine against H3 IAV-S.

Dual-functional emulsifier based nano-emulsion adjuvant effectively enhanced immunogenicity of recombinant respiratory syncytial virus vaccine in mice

Oil-in-water nano-emulsion adjuvant (NEA) has been utilized for many years in the development of subunit or/and recombinant vaccines. Nevertheless, worries have been expressed about the safety and potential biological activities of the emulsifier. Herein, tocopheryl polyethylene glycol 1000 succinate (TPGS), which acts not only as an emulsifier but also as an immunostimulant, was used for the preparation of NEA. Benefiting from the hydrophilic-hydrophobic nature of TPGS, NEA possess a homogeneous structure with an extremely narrow size distribution (approximately 160 nm in diameter, polydispersity index <0.15), and exhibits excellent stability over 6 months under test conditions. When such an NEA was used with a recombinant respiratory syncytial virus (RSV) vaccine, the adjuvanted vaccine induced enhanced humoral and cellular immunity in mice compared to the non-adjuvanted vaccine. This is the initial documented finding of TPGS adjuvanticity in an intramuscularly injected vaccine. Furthermore, the TPGS-based NEA showed elevated adjuvant potency compared to the MF59-like emulsion adjuvant assessed. These results imply the potential of NEA as an alternative adjuvant for developing recombinant vaccines with enhanced immunity.

Regulatory T Cells Nanoextinguisher to Manipulate Multiple Immune Evasion for Immunotherapy.

Regulatory T cells (Treg) play key roles in inhibiting effective antitumor immunity. However, therapeutic Treg depletion fails to consistently enhance immune responses due to the emergence of a wave of peripherally converted Treg cells postdepletion, along with undesired off-target side effects. Here, we report a nanoextinguisher decorated with functional peptides via tumor microenvironment responsive linkers to selectively block Treg function and maintain Treg levels rather than deplete them. The nanoextinguisher specifically neutralizes TGF-β to inhibit the recruitment of Treg cells and the conversion of naive T cells into Treg cells, thus promoting antitumor immunity. Moreover, the nanoextinguisher can alleviate tumor resistance to immunogenic photodynamic therapy, vaccination therapy, and checkpoint inhibition. The nanoextinguisher showed 30-fold potentiation in antitumor effect compared to standalone photodynamic therapy or vaccination therapy. Overall, utilizing a nanoextinguisher to inhibit Treg function without triggering reconversion represents a generalizable method to reverse immune evasion, yielding antitumor efficacy.

Viral Vector-Based Chlamydia trachomatis Vaccines Encoding CTH522 Induce Distinct Immune Responses in C57BL/6J and HLA Transgenic Mice.

Chlamydia trachomatis remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. In this study, we evaluated two novel MVA-based recombinant vaccines expressing spCTH522 and CTH522:B7 antigens. Our results show that while both vaccines induced CD4+ T-cell responses in C57BL/6J mice, they failed to generate antigen-specific systemic CD8+ T cells. Only the membrane-anchored CTH522 elicited strong IgG2b and IgG2c antibody responses. In an HLA transgenic mouse model, both recombinant MVAs induced Th1-directed CD4+ T cell and multifunctional CD8+ T cells, while only the CTH522:B7 vaccine generated antibody responses, underscoring the importance of antigen localization. Collectively, our data indicate that distinct antigen formulations can induce different immune responses depending on the mouse strain used. This research contributes to the development of effective vaccines by highlighting the importance of careful antigen design and the selection of appropriate animal models to study specific vaccine-induced immune responses. Future studies should investigate whether these immune responses provide protection in humans and should explore different routes of immunization, including mucosal and systemic immunization.

Advancements in Newcastle Disease Vaccination: Evaluating Traditional and Thermostable Vaccines for Enhanced Control and Efficacy

Newcastle disease (ND) is a critical viral disease in poultry, affecting various avian species worldwide and causing substantial economic losses annually in commercial and backyard poultry operations. Despite its global prevalence, ND can be controlled through proper vaccination and biosecurity management. Over the past 60-65 years, both live attenuated and inactivated ND virus vaccines have been extensively used to mitigate the economic impact of ND. Although live vaccines demonstrate high efficacy against the disease, achieving comprehensive control of ND outbreaks and their financial consequences remains challenging. The primary limitation of most commercially available live vaccines is their heat sensitivity, necessitating a cold chain for quality maintenance, which poses difficulties in village conditions or remote areas of developing tropical countries. This review discusses various methods of ND vaccine administration, their efficacy, and immunogenicity, focusing on the efficacy and stability of thermostable ND vaccines. A thorough understanding of these factors is essential for the long-term control and eradication of ND.

The impact of acellular pertussis vaccination in pregnancy on the immunogenicity of acellular versus whole-cell pertussis vaccines in infancy: A protocol for a phase IV randomised, controlled mother-infant pertussis vaccine trial (The Gambian Pertussis Study, GaPs)

Background Worldwide we have yet to achieve optimal control of pertussis, an important vaccine-preventable respiratory disease that has a particularly high burden of morbidity and mortality in infants under 1 year. Pertussis immunisation in pregnancy is an effective tool to protect infants in early life. However, there are concerns regarding the impact of maternal antibodies on the infant’s subsequent vaccine responses. The exact nature, duration, and clinical significance of this interaction is poorly understood. Methods We will conduct a phase IV randomised-controlled double-blinded (pregnant women) open-label (infants) trial, GaPs, in a cohort of 600 mother-infant pairs in The Gambia. Healthy pregnant women aged between 18 and 40 years will be recruited from two government antenatal healthcare centres in the Gambian peri-urban western region. They will be randomised to receive either a pertussis booster (TdaP-IPV) or Tetanus-Toxoid (TT, control) at 28-34 weeks’ gestation. Their infants will be further randomised to receive either acellular (aP) or whole-cell pertussis (wP) vaccines as part of the primary immunisation series at 8, 12 and 16 weeks of age and then followed up for 9-months postnatally. Clinical and safety data will be collected from each maternal-infant pair alongside blood samples and mucosal lining fluid, at baseline and multiple time points post-vaccination. Outcomes The trial aims to evaluate the quantity, quality, and persistence of immune responses, at both systemic and mucosal levels, to aP versus wP-containing priming schedules in Gambian infants up to 9-months of age, as well as the impact of pertussis immunisation in pregnancy on these responses. The primary endpoint measured will be the difference in the geometric mean concentration of anti-pertussis-toxin (PT) antibody in aP compared to wP-vaccinated infants at 16-weeks and 9-months postnatally. A further in-depth systems vaccinology approach will be embedded within the trial’s secondary and exploratory endpoints.

Expression, Purification, and Evaluation of Antibody Responses and Antibody-Immunogen Complex Simulation of a Designed Multi-Epitope Vaccine against SARS-COV-2.

The spread of the COVID-19 disease is the result of an infection caused by the SARS-CoV2 virus. Four crucial proteins, spike [S], membrane [M], nucleocapsid [N], and envelope [E] in coronaviruses have been considered to a large extent. This research aimed to express the recombinant protein of a multiepitope immunogen construct and evaluate the immunogenicity of the multiepitope vaccine that was previously designed as a candidate immunogenic against SARS-Cov-2. Plasmid pET26b was transferred to the expression host E. coli BL21 [DE3] and the recombinant protein was expressed with IPTG induction. The recombinant protein was purified by Ni-NTA column affinity chromatography, and western blotting was used to confirm it. Finally, mice were immunized with recombinant protein in three doses. Then, the interaction of the 3D structure of the vaccine with the human neutralizing antibodies3D structures [7BWJ and 7K8N] antibody was evaluated by docking and molecular dynamics simulation. The optimized gene had a codon compatibility index of 0.96. The expression of the recombinant protein of the SARS-Cov-2 vaccine in an E. coli host led to the production of the recombinant protein with a weight of about 70 kDa with a concentration of 0.7 mg/ml. Immunization of mice with recombinant protein of SARS-Cov-2 vaccine-induced IgG serum antibody response. Statistical analysis showed that the antibody titer in comparison with the control sample has a significant difference, and the antibody titer was acceptable up to 1/256000 dilution. The simulation of vaccine binding with human antibodies by molecular dynamics showed that Root Mean Square Deviation [RMSD], Root Mean Square Fluctuation [RMSF], Radius of Gyration, and H-bond as well as van der Waals energies and electrostatic of Molecular mechanics Poisson- Boltzmann surface area [MM/PBSA] analysis have stable interaction. This recombinant protein can probably be used as an immunogen candidate for the development of vaccines against SARS-CoV2 in future research.

Mechanism of mRNA vaccine, current study and direction of development

Following the COVID-19 outbreak, two mRNA vaccines were marketed in late 2020 after receiving FDA-approved emergency access, pioneering the use of mRNA vaccines in humans. Since then, more and more companies have joined the development and clinical trials of mRNA vaccines. At this stage, the development of mRNA vaccines is not only limited to COVID-19, but also covers infectious diseases, influenza, and cancer. Up to now, the regulation of immunogenicity of mRNA vaccines is a problem to be solved, and the controversy is mainly about typeIFN. This paper mainly introduces the classification, mechanism and characteristics of mRNA vaccines to show the basic principle of mRNA vaccines, and lists the applications of mRNA vaccines and the types of vaccines that are undergoing clinical trials, which reflects their huge application potential. The potential of mRNA vaccines is shown. With this paper, the author summarizes the current status of mRNA vaccines in order to show readers the basic principles and potentials of mRNA vaccines.

Immunogenicity of a peptide-based vaccine for measles: a pilot evaluation in a mouse model

Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of ‘help’ enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles.

Viral infection after hematopoietic stem cell transplantation.

Viral infections are important complications after allogeneic hematopoietic stem cell transplantation. New infections develop such as SARS-CoV-2 with the potential for severe consequences. In this review, newly published information regarding management of viral infections is discussed. Letermovir and maribavir are antiviral agents that have positively impacted the management of cytomegalovirus infections. These should today be included in treatment algorithms. The first antiviral cellular therapy for anti-CD20 refractory EBV-associated lymphoproliferative disease is now licensed and available. Vaccination as well as introduction of antiviral agents, mAbs and possibly the development of different viral strains have reduced mortality in COVID-19 in this patient population. Well designed studies have shown the improved immunogenicity of high-dose influenza vaccines. There is still an unmet medical need for patients infected with human metapneumovirus and parainfluenza viruses. Although improvements in patient management for several important posttransplantation viral infections have been reported, an unmet medical need still exists for other viruses occurring in this high-risk population.

A randomized study to evaluate the safety and immunogenicity of a pentavalent meningococcal vaccine

A randomized, active-controlled, double-blind, first-in-human, phase 1 study was conducted in healthy Korean adults to evaluate the safety, tolerability, and immunogenicity of EuNmCV-5, a new pentavalent meningococcal vaccine targeting serogroups A, C, W, X, and Y. Sixty participants randomly received a single dose of either EuNmCV-5 or MenACWY-CRM, a quadrivalent vaccine containing serogroups A, C, W, and Y. Safety was assessed through monitoring anaphylactic reactions, adverse events for 28 days, and serious adverse events over 180 days. Immunogenicity was assessed via rabbit complement-dependent serum bactericidal antibody (rSBA) assay. EuNmCV-5 was safe, well-tolerated, and elicited a substantial antibody titer increase. The seroprotection rates exceeded 96.7%, and the seroconversion rates were over 85% for all the targeted serogroups. It showed higher seroconversion rates against serogroups A and C (p = 0.0016 and 0.0237, respectively) and elicited a substantial increase in GMT for all targeted serogroups compared to the MenACWY-CRM.ClinicalTrials.gov identifier: NCT05739292.

The role of the gut microbiota in regulating responses to vaccination: current knowledge and future directions.

Antigen-specific B and Tcell responses play a critical role in vaccine-mediated protection against infectious diseases, but these responses are highly variable between individuals and vaccine immunogenicity is frequently sub-optimal in infants, the elderly and in people living in low- and middle-income countries. Although many factors such as nutrition, age, sex, genetics, environmental exposures, and infections may all contribute to variable vaccine immunogenicity, mounting evidence indicates that the gut microbiota is an important and targetable factor shaping optimal immune responses to vaccination. In this review, we discuss evidence from human, preclinical and experimental studies supporting a role for a healthy gut microbiota in mediating optimal vaccine immunogenicity, including the immunogenicity of COVID-19 vaccines. Furthermore, we provide an overview of the potential mechanisms through which this could occur and discuss strategies that could be used to target the microbiota to boost vaccine immunogenicity where it is currently sub-optimal.

Hybrid Predictive Machine Learning Model for the Prediction of Immunodominant Peptides of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a common respiratory pathogen that infects the human lungs and respiratory tract, often causing symptoms similar to the common cold. Vaccination is the most effective strategy for managing viral outbreaks. Currently, extensive efforts are focused on developing a vaccine for RSV. Traditional vaccine design typically involves using an attenuated form of the pathogen to elicit an immune response. In contrast, peptide-based vaccines (PBVs) aim to identify and chemically synthesize specific immunodominant peptides (IPs), known as T-cell epitopes (TCEs), to induce a targeted immune response. Despite their potential for enhancing vaccine safety and immunogenicity, PBVs have received comparatively less attention. Identifying IPs for PBV design through conventional wet-lab experiments is challenging, costly, and time-consuming. Machine learning (ML) techniques offer a promising alternative, accurately predicting TCEs and significantly reducing the time and cost of vaccine development. This study proposes the development and evaluation of eight hybrid ML predictive models created through the permutations and combinations of two classification methods, two feature weighting techniques, and two feature selection algorithms, all aimed at predicting the TCEs of RSV. The models were trained using the experimentally determined TCEs and non-TCE sequences acquired from the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) repository. The hybrid model composed of the XGBoost (XGB) classifier, chi-squared (ChST) weighting technique, and backward search (BST) as the optimal feature selection algorithm (ChST-BST-XGB) was identified as the best model, achieving an accuracy, sensitivity, specificity, F1 score, AUC, precision, and MCC of 97.10%, 0.98, 0.97, 0.98, 0.99, 0.99, and 0.96, respectively. Additionally, K-fold cross-validation (KFCV) was performed to ensure the model's reliability and an average accuracy of 97.21% was recorded for the ChST-BST-XGB model. The results indicate that the hybrid XGBoost model consistently outperforms other hybrid approaches. The epitopes predicted by the proposed model may serve as promising vaccine candidates for RSV, subject to in vitro and in vivo scientific assessments. This model can assist the scientific community in expediting the screening of active TCE candidates for RSV, ultimately saving time and resources in vaccine development.

Long-Term Safety and Immunogenicity of AZD1222 (ChAdOx1 nCoV-19): 2-Year Follow-Up from a Phase 3 Study.

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity. After 2 years, no emergent safety signals were observed for AZD1222, and no cases of thrombotic thrombocytopenia syndrome were reported. The assessment of anti-SARS-CoV-2 nucleocapsid antibody titers confirmed the durability of AZD1222 efficacy for up to 6 months, after which infection rates in the AZD1222 group increased over time. Despite this, all-cause and COVID-19-related mortality remained low through the study end, potentially reflecting the post-Omicron decoupling of SARS-CoV-2 infection rates and severe COVID-19 outcomes. Geometric mean titers were elevated for anti-SARS-CoV-2 neutralizing antibodies at the 1-year study visit and the anti-spike antibodies were elevated at year 2, providing further evidence of increasing SARS-CoV-2 infections over long-term follow-up. Overall, this 2-year follow-up of the AZD1222 phase 3 study confirms that the long-term safety profile remains consistent with previous findings and supports the continued need for COVID-19 booster vaccinations due to waning efficacy and humoral immunity.