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Helicobacter pylori (H. pylori) is an infectious bacterium that colonizes the stomach of approximately half of the global population. It has been classified as a Group I carcinogen by the World Health Organization due to its strong association with an increased incidence of gastric cancer and exacerbation of stomach diseases. The primary treatment for H. pylori infection currently involves triple or quadruple therapy, primarily consisting of antibiotics and proton pump inhibitors. However, the increasing prevalence of antibiotic resistance poses significant challenges to this approach, underscoring the urgent need for an effective vaccine. In this study, a novel multi-epitope H. pylori vaccine was designed using immunoinformatics. The vaccine contains epitopes derived from nine essential proteins. Software tools and online servers were utilized to predict, evaluate, and analyze the physiochemical properties, secondary and tertiary structures, and immunogenicity of the candidate vaccine. These comprehensive assessments ultimately led to the formulation of an optimal design scheme for the vaccine. Through constructing a novel multi-epitope vaccine based on immunoinformatics, this study offers promising prospects and great potential for the prevention of H. pylori infection. This study also provides a reference strategy to develop multi-epitope vaccines for other pathogens. [ABSTRACT FROM AUTHOR]

Visceral Leishmaniasis is a serious public health problem caused by Leishmania species parasites. Approximately 500 thousand people get Visceral Leishmaniasis (VL) every year. An effective and reliable vaccine against the disease has still not been formulated. Choosing the right adjuvant is important to increase immunogenicity in vaccines prepared with total antigens. In this study, we investigate the ideal adjuvant for use in vaccine formulations against VL. For this purpose, Leishmania antigens (FTLA) obtained from L. infantum parasites by the freeze-thaw method and three different adjuvants (alum-saponin and calcium phosphate) were used. The effectiveness of the formulations was investigated in vitro by cell viability analysis and determination of nitric oxide and cytokine production abilities in J774 macrophage cells. According to the study results, it was determined that formulations prepared with calcium phosphate produced 72% more NO and approximately 7.2 times more IL-12 cytokine. The results obtained showed that calcium phosphate salts can be used as ideal adjuvants in vaccine research against leishmaniasis. [ABSTRACT FROM AUTHOR]

Maintenance hemodialysis (MHD) patients exhibit compromised immune responses, leading to lower immunogenicity to the COVID‐19 vaccine than the general population. The metabolomic factors influencing COVID‐19 vaccine response in MHD patients remain elusive. A cross‐sectional study was conducted with 30 MHD patients, divided into three vaccine regimen groups (N= 10 per group): homologous CoronaVac® (SV‐SV), homologous ChAdOx1 nCoV‐19 (AZ‐AZ), and heterologous prime‐boost (SV‐AZ). Plasma samples were collected at baseline and at 28 days after the final dose to analyze 92 metabolomic levels using targeted metabolomics. The study included 30 MHD patients (mean age 56.67 ± 10.79 years) with similar neutralizing antibody (nAb) levels across vaccine regimens. The most significant differences in metabolomics were found between AZ‐AZ and SV‐SV, followed by SV‐AZ versus SV‐SV, and AZ‐AZ versus SV‐AZ. Overall, the metabolomic changes involved amino acids like glutamate and phenylalanine, and phospholipids. Prevaccination metabolomic profiles, including PG (38:1), lysoPE (20:2), lysoPC (18:2), lysoPI (18:1), and PC (34:2), exhibited negative correlations with postvaccination nAb levels. Different COVID‐19 vaccine regimens had unique interactions with the immune response in MHD patients. Amino acid and phospholipid metabolisms play crucial roles in nAb formation, with the phospholipid metabolism being a potentially predictive marker of vaccine immunogenicity among MHD patients. [ABSTRACT FROM AUTHOR]

Background Since influenza and respiratory syncytial virus (RSV) carry significant burden in older adults with overlapping seasonality, vaccines for both pathogens would ideally be coadministered in this population. Here we evaluate the immunogenicity and safety of concomitant administration of Ad26.RSV.preF/RSV preF protein and high-dose seasonal influenza vaccine (Fluzone-HD) in adults ≥65 years old. Methods Participants were randomized 1:1 to the Coadministration or Control group. The Coadministration group received concomitant Ad26.RSV.preF/RSV preF protein and Fluzone-HD on day 1 and placebo on day 29, while the Control group received Fluzone-HD and placebo on day 1 and Ad26.RSV.preF/RSV preF protein on day 29. Influenza hemagglutination-inhibiting and RSV preF–binding antibody titers were measured postvaccination and tested for noninferiority between both groups. Safety data were collected throughout the study and analyzed descriptively. Results Coadministered Ad26.RSV.preF/RSV preF protein and Fluzone-HD vaccines induced noninferior immune responses compared to each vaccine administered alone. Seroconversion and seroprotection rates against influenza were similar between groups. Both vaccines remained well tolerated upon concomitant administration. Conclusions Coadministration of Ad26.RSV.preF/RSV preF protein and Fluzone-HD showed an acceptable safety profile and did not hamper the immunogenicity of either vaccine, thus supporting that both vaccines can be concomitantly administered in adults ≥65 years old. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine. Methods This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 μg vaccination 12–18 months after first vaccination. Results The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12–18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination. Conclusions This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used. Clinical Trials Registration NCT04138056. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With the rapid global spread of COVID-19 and the continuous emergence of variants, there is an urgent need to develop safe and effective vaccines. Here, we developed a novel mRNA vaccine, HC009, based on new formulation by the QTsome delivery platform. Immunogenicity results showed that the prime-boost immunization strategy with HC009 was able to induce robust and durable humoral immunity, as well as Th1-biased cellular responses in rodents or nonhuman primates (NHPs). After further challenge with live SARS-CoV-2 virus, HC009 provided adequate protection against virus infection in hACE2 transgenic mice. Therefore, HC009 could provide significant immune protection against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The HIV-1 envelope glycoprotein (Env) is the sole neutralizing determinant on the surface of the virus. The Env gp120 and gp41 subunits mediate receptor binding and membrane fusion and are generated from the gp160 precursor by cellular furins. This cleavage event is required for viral entry. One approach to generate HIV-1 neutralizing antibodies following immunization is to express membranebound Env anchored on the cell-surface by genetic means using the natural HIV gp41 transmembrane (TM) spanning domain. To simplify the process of Env trimer membrane expression we sought to remove the need for Env precursor cleavage while maintaining native-like conformation following genetic expression. To accomplish these objectives, we selected our previously developed 'native flexibly linked' (NFL) stabilized soluble trimers that are both near-native in conformation and cleavage-independent. We genetically fused the NFL construct to the HIV TM domain by using a short linker or by restoring the native membrane external proximal region, absent in soluble trimers, to express the full HIV Env ectodomain on the plasma membrane. Both forms of cellsurface NFL trimers, without and with the MPER, displayed favorable antigenic profiles by flow cytometry when expressed from plasmid DNA or mRNA. These results were consistent with the presence of well-ordered cell surface native-like trimeric Env, a necessary requirement to generate neutralizing antibodies by vaccination. Inoculation of rabbits with mRNA lipid nanoparticles (LNP) expressing membrane-bound stabilized HIV Env NFL trimers generated tier 2 neutralizing antibody serum titers in immunized animals. Multiple inoculations of mRNA LNPs generated similar neutralizing antibody titers compared to immunizations of matched NFL soluble proteins in adjuvant. Given the recent success of mRNA vaccines to prevent severe COVID, these are important developments for genetic expression of native-like HIV Env trimers in animals and potentially in humans. [ABSTRACT FROM AUTHOR]

Antigen‐specific B and T cell 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. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) immunization frequently requires two standard doses. Due to the likelihood that the population may lose immunity after receiving a standard mass vaccination and the potential for the introduction of a new strain, several scientists are currently advocating the use of a booster dosage of the vaccine. The authors of this retrospective study used a clinical model for immune response prediction to forecast how solid cancer patients will respond to the fourth dosage of the COVID-19 immunization. In the case of homologous primary backgrounds, the prospective rates of extension of protective efficacy for using viral vector and messenger ribonucleic acid (mRNA) COVID-19 vaccines for vaccinees with underlying solid tumor are equal to 11.5 and 16.5%, respectively. In the event of heterologous primary backgrounds, the prospective rates of extension of protective efficacy for using viral vector and mRNA COVID-19 vaccines are equal to 2.2 and 7.2%, respectively, for patients with underlying solid cancer. In conclusion, the fourth dose of the COVID-19 vaccine regimen had an effect on the immunogenicity of vaccine recipients with underlying malignancy. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori) is responsible for various chronic or acute diseases, such as stomach ulcers, dyspepsia, peptic ulcers, gastroesophageal reflux, gastritis, lymphoma, and stomach cancers. Although specific drugs are available to treat the bacterium's harmful effects, there is an urgent need to develop a preventive or therapeutic vaccine. Therefore, the current study aims to create a multi-epitope vaccine against H. pylori using lipid nanoparticles. Five epitopes from five target proteins of H. pylori, namely, Urease, CagA, HopE, SabA, and BabA, were used. Immunogenicity, MHC (Major Histocompatibility Complex) bonding, allergenicity, toxicity, physicochemical analysis, and global population coverage of the entire epitopes and final construct were carefully examined. The study involved using various bioinformatic web tools to accomplish the following tasks: modeling the three-dimensional structure of a set of epitopes and the final construct and docking them with Toll-Like Receptor 4 (TLR4). In the experimental phase, the final multi-epitope construct was synthesized using the solid phase method, and it was then enclosed in lipid nanoparticles. After synthesizing the construct, its loading, average size distribution, and nanoliposome shape were checked using Nanodrop at 280 nm, dynamic light scattering (DLS), and atomic force microscope (AFM). The designed vaccine has been confirmed to be non-toxic and anti-allergic. It can bind with different MHC alleles at a rate of 99.05%. The construct loading was determined to be about 91%, with an average size of 54 nm. Spherical shapes were also observed in the AFM images. Further laboratory tests are necessary to confirm the safety and immunogenicity of the multi-epitope vaccine. [ABSTRACT FROM AUTHOR]

Summary: Immune responses to primary COVID‐19 vaccination were investigated in 58 patients with follicular lymphoma (FL) as part of the PETReA trial of frontline therapy (EudraCT 2016–004010‐10). COVID‐19 vaccines (BNT162b2 or ChAdOx1) were administered before, during or after cytoreductive treatment comprising rituximab (depletes B cells) and either bendamustine (depletes CD4+ T cells) or cyclophosphamide‐based chemotherapy. Blood samples obtained after vaccine doses 1 and 2 (V1, V2) were analysed for antibodies and T cells reactive to the SARS‐CoV‐2 spike protein using the Abbott Architect and interferon‐gamma ELISpot assays respectively. Compared to 149 healthy controls, patients with FL exhibited lower antibody but preserved T‐cell responses. Within the FL cohort, multivariable analysis identified low pre‐treatment serum IgA levels and V2 administration during induction or maintenance treatment as independent determinants of lower antibody and higher T‐cell responses, and bendamustine and high/intermediate FLIPI‐2 score as additional determinants of a lower antibody response. Several clinical scenarios were identified where dichotomous immune responses were estimated with >95% confidence based on combinations of predictive variables. In conclusion, the immunogenicity of COVID‐19 vaccines in FL patients is influenced by multiple disease‐ and treatment‐related factors, among which B‐cell depletion showed differential effects on antibody and T‐cell responses. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nine-valent human papillomavirus (9vHPV) vaccines can be administered in 2 doses 6 to 12 months apart in adolescents. The impact of extended dose intervals is unknown. We report immunogenicity and safety data in adolescents of a second 9vHPV vaccine dose administered ≥1 year after the first. METHODS: This open-label safety and immunogenicity study (NCT04708041) assessed extended-interval 2-dose regimens of 9vHPV vaccine among adolescents (10 to 15 years) who received 2 9vHPV vaccine doses: the first ≥1 year before enrollment, and second, at enrollment (day 1). We measured serologic responses to vaccine-targeted human papillomavirus (HPV) types at enrollment day 1 (pre-dose 2) and 1 month post-dose 2 (month 1) using a competitive LuminexV® immunoassay. We estimated effects of dose interval on geometric mean titers (GMTs) using regression modeling. Participants reported adverse events (AEs) through 15 days after vaccination. RESULTS: We enrolled 146 adolescents (mean age 13.3 years) with median 25 months since first 9vHPV vaccine dose (range: 12-53 months). Across vaccine-targeted HPV types, GMTs increased from day 1 to month 1; seropositivity at month 1 was 100%. Anti-HPV GMTs at month 1 were not affected by differences in dose interval of 12 to 53 months, based on regression modeling. The most common AEs were mild-to-moderate injection site reactions; no serious AEs were reported. CONCLUSIONS: Extending the interval between first and second 9vHPV vaccine doses to 12 to 53 months did not affect antibody responses, with favorable safety profile. These results support feasibility of extended interval regimens for 9vHPV vaccine. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide (Ozempic®), have emerged as effective treatments for diabetes and weight management. However, recent evidence indicates that GLP-1R signalling influences various tissues, including the immune system. Notably, GLP-1 has a short half-life (< 5 minutes) and exists in the picomolar range, while GLP-1RAs like semaglutide have extended half-lives of several days and are administered at supraphysiological doses. This review explores the potential impact of these medications on vaccine efficacy. We examine evidence suggesting that GLP-1RAs may attenuate vaccine responses through direct effects on immune cells and modulation of other tissues. Additionally, we discuss how GLP-1R signalling may create a tolerogenic environment, potentially reducing vaccine immunogenicity. Given the widespread use of GLP-1RAs, it is crucial to understand their impact on immune responses and the translational implications for vaccination outcomes. [Display omitted] • GLP-1RAs play a key role in managing diabetes and assisting weight loss. • Immune cells also express GLP-1R and are also affected by GLP-1RAs. • Various immune cells exhibit tolerogenic/anti-inflammatory responses to GLP-1RAs. • Signalling cascades downstream of GLP-1R direct immune-attenuating cAMP signalling. • GLP-1RAs impact vaccine efficacy through both immune and non-immune mechanisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Anti‐IgE immunotherapy with monoclonal antibodies represents a breakthrough in treatment of severe allergic diseases. However, drawbacks such as short half‐life and high price are not negligible. Our objective is to develop an anti‐IgE vaccine based on virus‐like particles (VLPs) which can induce long‐lasting neutralizing IgG anti‐IgE antibodies reducing allergic responses without causing intrinsic mast cell activation due to IgE cross‐linking. Methods: The vaccines were made by chemically coupling three synthetic mouse IgE‐Fc fragments to plant‐derived immunologically optimized CuMVTT VLPs. The immunogenicity of the vaccines was tested by immunizing naive or allergic mice either with the coupled vaccines or the VLP control followed by systemic or local allergen challenge. Results: Mice immunized with the vaccines exhibited high titers of anti‐IgE antibodies in the sera and high levels of anti‐IgE secreting plasma cells in lymphoid organs. Moreover, free IgE in serum were reduced by the induced anti‐IgE antibodies; therefore, less IgE was bound to FcεRI on the surface of basophils. In line with these reduced IgE levels on effector cells after vaccination, immunized mice were protected from challenge with allergens. Importantly, despite presence of anti‐IgE antibodies, no signs of acute or chronic allergic response were seen in immunized allergic mice. Conclusion: The generated vaccines can effectively induce anti‐IgE antibodies that did not cause allergic responses in sensitized mice but were able to decrease the level of free and cell bound IgE and protected sensitized animals from allergic responses upon allergen challenge. [ABSTRACT FROM AUTHOR]

Nanovaccines have been designed to overcome the limitations associated with conventional vaccines. Effective delivery methods such as engineered carriers or smart nanoparticles (NPs) are critical requisites for inducing self‐tolerance and optimizing vaccine immunogenicity with minimum side effects. NPs can be used as adjuvants, immunogens, or nanocarriers to develop nanovaccines for efficient antigen delivery. Multiloaded nanovaccines carrying multiple tumor antigens along with immunostimulants can effectively increase immunity against tumor cells. They can be biologically engineered to boost interactions with dendritic cells and to allow a gradual and constant antigen release. Modifying NPs surface properties, using high‐density lipoprotein‐mimicking nanodiscs, and developing nano‐based artificial antigen‐presenting cells such as dendritic cell‐derived‐exosomes are amongst the new developed technologies to enhance antigen‐presentation and immune reactions against tumor cells. The present review provides an overview on the different perspectives, improvements, and barriers of successful clinical application of current cancer therapeutic and vaccination options. The immunomodulatory effects of different types of nanovaccines and the nanoparticles incorporated into their structure are described. The advantages of using nanovaccines to prevent and treat common illnesses such as AIDS, malaria, cancer and tuberculosis are discussed. Further, potential paths to develop optimal cancer vaccines are described. Given the immunosuppressive characteristics of both cancer cells and the tumor microenvironment, applying immunomodulators and immune checkpoint inhibitors in combination with other conventional anticancer therapies are necessary to boost the effectiveness of the immune response. [ABSTRACT FROM AUTHOR]

With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs). In addition, the most critical issue now is a COVID-19 vaccine that generates strong and durable immunity. A growing number of clinical studies confirm the potential of gut microbes to enhance the efficacy of COVID-19 vaccines. However, it is still unclear how gut bacteria interact with immune cells and what treatments are based on gut microbes. Here, we outline recent advances in the effects and mechanisms of the gut microbiota and its metabolites (tryptophan metabolites, bile acids, short-chain fatty acids, and inosine) on different immune cells (dendritic cells, CD4+T cells, and macrophages). It also highlights innovative intervention strategies and clinical trials of microbiota-based checkpoint blocking therapies for tumor immunity, and ongoing efforts to maintain the long-term immunogenicity of COVID-19 vaccines. Finally, the challenges to be overcome in this area are discussed. These provide an important basis for further research and clinical translation of gut microbiota. [ABSTRACT FROM AUTHOR]

This review article will summarize the vaccines and monoclonal antibodies currently under evaluation for the prevention of RSV disease in older infants, toddlers and young children. We will review the rationale for passive protection during the first months of life, and the role of active immunization afterwards, either with live attenuated, protein-based or mRNA vaccines. [ABSTRACT FROM AUTHOR]

Background With the future epidemiology and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uncertain, the use of safe and effective coronavirus disease 2019 (COVID-19) vaccines in pediatric populations remains important. Methods We report data from two open-label substudies of an ongoing phase 1/2/3 master study (NCT05543616) investigating the safety and immunogenicity of a variant-adapted bivalent COVID-19 vaccine encoding ancestral and Omicron BA.4/BA.5 spike proteins (bivalent BNT162b2). The open-label groups presented here evaluate dose 4 with bivalent BNT162b2 in 6-month- to <12-year-olds who previously received three original (monovalent) BNT162b2 doses. In 6-month- to <5-year-olds, primary immunogenicity objectives were to demonstrate superiority (neutralizing titer) and noninferiority (seroresponse rate) to Omicron BA.4/BA.5 and noninferiority (neutralizing titer and seroresponse rate) to SARS-CoV-2 ancestral strains in participants who received bivalent BNT162b2 dose 4 compared with a matched group who received three doses of original BNT162b2 in the pivotal pediatric study (NCT04816643). In 5- to <12-year-olds, primary immunogenicity comparisons were descriptive. Reactogenicity and safety following vaccination were evaluated. Results In 6-month- to <5-year-olds, dose 4 with bivalent BNT162b2 met predefined immunogenicity superiority and noninferiority criteria against Omicron BA.4/BA.5 and ancestral strains when compared with dose 3 of original BNT162b2. In 5- to <12-year-olds, bivalent BNT162b2 induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers comparable with dose 3 of original BNT162b2. The safety profile for dose 4 of bivalent BNT162b2 given as dose 4 was consistent with that of original BNT162b2 in 6-month- to <12-year-olds. Reactogenicity events were generally mild to moderate. No adverse events led to discontinuation. Conclusions These safety and immunogenicity data support a favorable benefit-risk profile for a variant-adapted BNT162b2 in children <12 years old. [ABSTRACT FROM AUTHOR]

Validation of bioanalytical methods is crucial, especially in the pharmaceutical industry, to determine their suitability for specific purposes and the accuracy of analytical results. The pseudovirion‐based neutralization assay (PBNA) is considered the gold standard for detecting and quantifying neutralizing antibodies against human papillomavirus in vaccine development for disease prevention. This paper introduces an improved triple‐color PBNA method, capable of simultaneous detection of two or three human papillomavirus (HPV types for use in the development of a 14‐valent HPV vaccine candidate. The primary objective was to comprehensively validate the triple‐color PBNA method for general vaccine immunogenicity assays. Results show that the method has good specificity, accuracy, precision, linearity, robustness, and applicability. This innovative triple‐color PBNA offers an improved approach for large‐scale immunogenicity assessment in vaccine development. This study lays a solid foundation that can serve as a guiding paradigm for assessing vaccine responses in preclinical and clinical phases, providing valuable insights to the field. [ABSTRACT FROM AUTHOR]

Background: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2. Methods: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis. Results: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2–59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log10LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10−5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log10LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log10LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log10LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log10LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10−5% vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log10LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log10LDA score = 2.14). Conclusion: Among three-dose BNT162b2 recipients, S. parasanguinis, B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response. [ABSTRACT FROM AUTHOR]

PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Senecavirus A (SVA) is a picornavirus that is endemic in swine, causing a vesicular disease clinically indistinguishable from other vesicular diseases, like foot-and-mouth disease. The widespread viral circulation, constant evolution, and economic losses caused to the swine industry emphasize the need for measures to control the agent. In this study, we evaluated the immunogenicity of a whole-virus-inactivated vaccine using a representative contemporary Brazilian SVA strain in Balb/ByJ mice. The animals were vaccinated with two doses by an intramuscular route. The humoral response induced by the vaccination was evaluated by an in-house ELISA assay for IgG detection. The cellular response was assessed by flow cytometry after in vitro SVA stimulation in splenocyte cultures from vaccinated and non-vaccinated groups. Protection against SVA was assessed in the experimental groups following an oral challenge with the homologous virus. The vaccination induced high levels of IgG antibodies and the proliferation of CD45R/B220+sIgM+, CD3e+CD69+, and CD3e+CD4+CD44+CD62L− cells. These results indicate the immunogenicity and safety of the vaccine formulation in a murine model and the induction of humoral and cellular response against SVA. [ABSTRACT FROM AUTHOR]

Background: EGFR has been suggested to contribute to COPD development and progression. Excessive ligand activation of the receptor leads to epithelial hyperproliferation and increased production of mucus, together with alterations in the primary cilia. The present study was designed to evaluate the safety and effect of depleting EGF in moderate-to-severe COPD patients, with an EGF-based vaccine. Patients and methods: A phase I trial was conducted in subjects with moderate or severe COPD. The anti-EGF vaccine schedule consisted of 4 biweekly doses followed by 4 monthly boosters. The primary endpoint was the evaluation of the safety and immunogenicity of the vaccine, together with the change in FEV1 and physical function at week 24. Results: Twenty-six patients with moderate or severe COPD were included in the trial. The vaccine was well tolerated and no serious related adverse events were reported. Ninety percent of the individuals developed a protective antibody response. The specific anti-EGF antibodies had high avidity and were able to inhibit EGFR phosphorylation. At the end of vaccination, serum EGF became undetectable. At week 24, there was a clinically significant improvement in lung function, with a mean change in trough FEV1 of 106 mL. Patients also increased their physical functioning. Conclusions: The EGF-based vaccine was immunogenic and provoked an EGF exhaustion in patients with moderate-to-severe COPD. Depleting EGF might result in a meaningful increase in FEV1, with good tolerability. The current results provide new avenues to treat chronic inflammatory lung diseases associated with EGFR aberrant signaling. [ABSTRACT FROM AUTHOR]

This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population. [ABSTRACT FROM AUTHOR]

Leptospirosis, a neglected zoonotic disease, is caused by pathogenic spirochetes belonging to the genus Leptospira and has one of the highest morbidity and mortality rates worldwide. Vaccination stands out as one of the most effective preventive measures for susceptible populations. Within the outer membrane of Leptospira spp., we find the LIC12287, LIC11711, and LIC13259 lipoproteins. These are of interest due to their surface location and potential immunogenicity. Thorough examination revealed the conservation of these proteins among pathogenic Leptospira spp.; we mapped the distribution of T- and B-cell epitopes along their sequences and assessed the 3D structures of each protein. This information aided in selecting immunodominant regions for the development of a chimeric protein. Through gene synthesis, we successfully constructed a chimeric protein, which was subsequently expressed, purified, and characterized. Hamsters were immunized with the chimeric lipoprotein, formulated with adjuvants aluminum hydroxide, EMULSIGEN®-D, Sigma Adjuvant System®, and Montanide™ ISA206VG. Another group was vaccinated with an inactivated Escherichia coli bacterin expressing the chimeric protein. Following vaccination, hamsters were challenged with a virulent L. interrogans strain. Our evaluation of the humoral immune response revealed the production of IgG antibodies, detectable 28 days after the second dose, in contrast to pre-immune samples and control groups. This demonstrates the potential of the chimeric protein to elicit a robust humoral immune response; however, no protection against challenge was achieved. While this study provides valuable insights into the subject, further research is warranted to identify protective antigens that could be utilized in the development of a leptospirosis vaccine. Key points: • Several T- and B-cell epitopes were identified in all the three proteins. • Four different adjuvants were used in vaccine formulations. • Immunization stimulated significant levels of IgG2/3 in vaccinated animals. [ABSTRACT FROM AUTHOR]

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

Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM (n = 28) and B-cell chronic lymphoproliferative disorders (n = 53) vs. health care practitioners (n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4+ T cells in the blood, as well as the absolute counts of B cells and dendritic cells, predicted vaccine immunogenicity at different time points. In contrast with the humoral response, the percentage and antigen-dependent differentiation of SARS-CoV-2-specific CD8+ T cells was not altered in MM patients. Taken together, this study defined the cellular composition associated with immune dysfunction in MM and provided biomarkers such as the B-cell percentage and absolute count to individualize vaccination calendars. [ABSTRACT FROM AUTHOR]

Background: The lack of complete protection against leishmaniasis and the challenges of anti-leishmaniasis drug treatment have made the treatment process more difficult. This study aimed to develop a new strategy for preparing a vaccine against cutaneous leishmaniasis using some of the antigenic proteins of the Leishmania parasite. Methods: This study was carried out in 2022 at Shahid Chamran University of Ahvaz, Ahvaz, Iran. After preparing suitable epitopes of the Leishmania parasite and examining their antiparasitic properties, the process of making a fusion vaccine was performed and with the help of various bioinformatics tools, physicochemical and structural properties as well as immunological and simulation properties were studied and finally optimized. Construction and cloning were performed in the E.coli K12 system and finally, the docking process was performed with Toll-like receptors (TLRs), major histocompatibility complex I (MHC-I), and MHC-II receptors. With the help of selected epitopes of the Leishmania parasite, which had a high percentage of population coverage, a stable, antigenic, and non-allergenic chimeric vaccine was predicted. Results: The results of the structural analysis of the TLR5\vaccine complex and simulation of its molecular dynamics showed a sufficiently stable binding. It also showed good potential for stimulation and production of active B cells and memory, as well as the potential for CD8+ T, CD4+ T cell production and development of Th2 and Th1-induced immune responses. Conclusion: Computational results showed that the designed immunogenic structure has the potential to adequately stimulate cellular and humoral immune responses against Leishmania parasitic disease. As a result of evaluating the effectiveness of the candidate vaccine through in vivo and in vitro immunological tests, it can be suggested as a vaccine against Leishmania major. [ABSTRACT FROM AUTHOR]

Oral rotavirus vaccines demonstrate diminished immunogenicity in low-income settings where human cytomegalovirus infection is acquired early in childhood and modulates immunity. We hypothesized that human cytomegalovirus infection around the time of vaccination may influence immunogenicity. We measured plasma human cytomegalovirus-specific immunoglobulin M antibodies in rotavirus vaccinated infants from 6 weeks to 12 months old and compared rotavirus immunoglobulin A antibody titers between human cytomegalovirus seropositive and seronegative infants. There was no evidence of an association between human cytomegalovirus serostatus at 9 months and rotavirus-specific antibody titers at 12 months (geometric mean ratio 1.01, 95% CI: 0.70, 1.45; P = 0.976) or fold-increase in RV-IgA titer between 9 and 12 months (risk ratio 0.999, 95%CI: 0.66, 1.52; P = 0.995) overall. However, HIV-exposed-uninfected infants who were seropositive for human cytomegalovirus at 9 months old had a 63% reduction in rotavirus antibody geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were seronegative for human cytomegalovirus (geometric mean ratio 0.37, 95% CI: 0.17, 0.77; P = 0.008). While the broader implications of human cytomegalovirus infections on oral rotavirus vaccine response might be limited in the general infant population, the potential impact in the HIV-exposed-uninfected infants cannot be overlooked. This study highlights the complexity of immunological responses and the need for targeted interventions to ensure oral rotavirus vaccine efficacy, especially in vulnerable subpopulations. Among rotavirus vaccinated infants, there was no evidence of an association between HCMV-IgM serostatus at 9 months with RV-IgA titer at 12 months (GMR 1.01, 95%CI: 0.70, 1.45; P  = 0.976). However, HIV-exposed-uninfected infants who were HCMV-IgM seropositive at 9 months old had a 63% reduction in RV-IgA geometric mean titers at 12 months compared to HIV-exposed-uninfected infants who were HCMV-IgM seronegative (geometric mean ratio 0.37, 95%CI: 0.17, 0.77; P  = 0.008). Created with BioRender.com Graphical Abstract [ABSTRACT FROM AUTHOR]

Objective Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known. Methods RA patients treated with JAKi (n  = 82) at the Department of Rheumatology, Skåne University Hospital, Lund and Malmö, Sweden, and healthy controls (n  = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed. Results Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P  < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a ≥4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination. Conclusion The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population. Trial registration ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038. [ABSTRACT FROM AUTHOR]

As a highly pathogenic avian virus, H5 influenza poses a serious threat to livestock, the poultry industry, and public health security. Hemagglutinin (HA) is both the dominant epitope and the main target of influenza-neutralizing antibodies. Here, we designed a nanoparticle hemagglutinin influenza vaccine to improve the immunogenicity of the influenza vaccine. In this study, HA5 subtype influenza virus was used as the candidate antigen and was combined with the artificially designed double-branch scaffold protein I53_dn5 A and B. A structurally correct and bioactive trimer HA5-I53_dn5B/Y98F was obtained through secretion and purification using an insect baculovirus expression system; I53_dn5A was obtained by purification using a prokaryotic expression system. HA5-I53_dn5B/Y98F and I53_dn5A self-assembled into spherical nanoparticles (HA5-I53_dn5) in vitro with a diameter of about 45 nm. Immunization and serum test results showed that both HA5-I53_dn5B/Y98F and HA5-I53_dn5 could induce HA5-specific antibodies; however, the immunogenicity of HA5-I53_dn5 was better than that of HA5-I53_dn5B/Y98F. Groups treated with HA5-I53_dn5B and HA5-I53_dn5 nanoparticles produced IgG antibody titers that were not statistically different from those of the nanoparticle-containing adjuvant group. This production of trimerized HA5-I53_dn5B and HA5-I53_dn5 nanoparticles using baculovirus expression provides a reference for the development of novel, safe, and efficient influenza vaccines. [ABSTRACT FROM AUTHOR]

Anamnestic 13-valent pneumococcal conjugate vaccine immunization did not affect the relapse risk in pediatric idiopathic nephrotic syndrome. Pneumococcal serotype (PS)-specific antibody titers increased significantly in all groups. Children receiving immunomodulatory treatments (IMTs) displayed significantly lower levels of PS-specific antibodies for 3/8 serotypes tested. PS-specific B-cell counts significantly increased only in healthy controls and patients receiving corticosteroids. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. COVID-19 naive adults aged 18–30 years were recruited from a previous study on primary vaccination regimens that compared 20 μg ID vaccinations with 100 μg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 μg) or the standard-of-care intramuscular (IM) booster dose (50 μg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18–40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. In January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150–11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003–6322) BAU/mL; 6629 (4913–8946) BAU/mL; and 5264 (4032–6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. Intradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness. [ABSTRACT FROM AUTHOR]

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

Serum-neutralizing antibody titers are a critical measure of vaccine immunogenicity and are used to determine flavivirus seroprevalence in study populations. An effective dengue virus (DENV) vaccine must confer simultaneous protection against viruses grouped within four antigenic serotypes. Existing flavivirus neutralization assays, including the commonly used plaque/focus reduction neutralization titer (PRNT/ FRNT) assay, require an individual assay for each virus, serotype, and strain and easily become a labor-intensive and time-consuming effort for large epidemiological studies or vaccine trials. Here, we describe a multiplex reporter virus particle neutralization titer (TetraPlex RVPNT) assay for DENV that allows simultaneous quantitative measures of antibody-mediated neutralization of infection against all four DENV serotypes in a single low-volume clinical sample and analyzed by flow cytometry. Comparative studies confirm that the neutralization titers of antibodies measured by the TetraPlex RVPNT assay are similar to FRNT/PRNT assay approaches performed separately for each viral strain. The use of this high-throughput approach enables the careful serological study in DENV endemic populations and vaccine recipients required to support the development of a safe and effective tetravalent DENV vaccine. IMPORTANCE As a mediator of protection against dengue disease and a serological indicator of prior infection, the detection and quantification of neutralizing antibodies against DENV is an important “gold standard” tool. However, execution of traditional neutralizing antibody assays is often cumbersome and requires repeated application for each virus or serotype. The optimized RVPNT assay described here is high-throughput, easily multiplexed across multiple serotypes, and targets reporter viral particles that can be robustly produced for all four DENV serotypes. The use of this transformative RVPNT assay will support the expansion of neutralizing antibody datasets to answer research and public health questions often limited by the more cumbersome neutralizing antibody assays and the need for greater quantities of test serum. [ABSTRACT FROM AUTHOR]

Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens are capable of inducing efficacious humoral and cellular immune responses in nonhuman primates. Several studies have evaluated the use of immune modulators to further enhance vaccine-induced T-cell responses. The hematopoietic growth factor Flt3L drives the expansion of various bone marrow progenitor populations, and administration of Flt3L was shown to promote expansion of dendritic cell populations in spleen and blood, which are targets of arenaviral vectors. Therefore, we evaluated the potential of Flt3 signaling to enhance the immunogenicity of arenaviral vaccines encoding SIV immunogens (SIVSME543 Gag, Env, and Pol) in rhesus macaques, with a rhesus-specific engineered Flt3L-Fc fusion protein. In healthy animals, administration of Flt3L-Fc led to a 10-to 100-fold increase in type 1 dendritic cells 7 days after dosing, with no antidrug antibody (ADA) generation after repeated dosing. We observed that administration of Flt3L-Fc fusion protein 7 days before arenaviral vaccine increased the frequency and activation of innate immune cells and enhanced T-cell activation with no treatment-related adverse events. Flt3L-Fc administration induced early innate immune activation, leading to a significant enhancement in magnitude, breadth, and polyfunctionality of vaccine-induced T-cell responses. The Flt3L-Fc enhancement in vaccine immunogenicity was comparable to a combination with αCTLA-4 and supports the use of safe and effective variants of Flt3L to augment therapeutic vaccine-induced T-cell responses. IMPORTANCE Induction of a robust human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell response through therapeutic vaccination is considered essential for HIV cure. Arenaviral vaccine vectors encoding simian immunodeficiency virus (SIV) immunogens have demonstrated strong immunogenicity and efficacy in nonhuman primates. Here, we demonstrate that the immunogenicity of arenaviral vectors encoding SIV immunogens can be enhanced by administration of Flt3L-Fc fusion protein 7 days before vaccination. Flt3L-Fc-mediated increase in dendritic cells led to robust improvements in vaccine-induced T- and B-cell responses compared with vaccine alone, and Flt3L-Fc dosing was not associated with any treatment-related adverse events. Importantly, immune modulation by either Flt3L-Fc or αCTLA-4 led to comparable enhancement in vaccine response. These results indicate that the addition of Flt3L-Fc fusion protein before vaccine administration can significantly enhance vaccine immunogenicity. Thus, safe and effective Flt3L variants could be utilized as part of a combination therapy for HIV cure. [ABSTRACT FROM AUTHOR]

Vaccine immunogenicity and reactogenicity depend on recipient and vaccine characteristics. We hypothesized that healthy adults reporting higher reactogenicity from seasonal inactivated influenza vaccine (IIV) developed higher antibody titers compared with those reporting lower reactogenicity. We performed a secondary analysis of a randomized phase 1 trial of a trivalent IIV delivered by microneedle patch (MNP) or intramuscular (IM) injection. We created composite reactogenicity scores as exposure variables and used hemagglutination inhibition (HAI) titers as outcome variables. We used mixed-model analysis of variance to estimate geometric mean titers (GMTs) and titer fold change and modified Poisson generalized estimating equations to estimate risk ratios of seroprotection and seroconversion. Estimates of H3N2 GMTs were associated with the Systemic and Local scores among the IM group. Within the IM group, those with high reaction scores had lower baseline H3N2 GMTs and twice the titer fold change by day 28. Those with high Local scores had a greater probability of seroconversion. These results suggest that heightened reactogenicity to IM IIV is related to low baseline humoral immunity to an included antigen. Participants with greater reactogenicity developed greater titer fold change after 4 weeks, although the response magnitude was similar or lower compared with low-reactogenicity participants. [ABSTRACT FROM AUTHOR]

Herpes zoster (HZ) is an infectious disease caused by the reactivation of varicella zoster virus (VZV), with 68% of cases occurring in adults over 50 years of age. HZ/su (Shingrix®) was approved by the Food and Drug Administration in 2017 for the prevention of HZ in individuals ≥ 50 years of age and showed very good protection from HZ. However, due to the use of the adjuvant AS01B, adverse reactions caused by Shingrix are a concern. Aluminum hydroxide is the most commonly used adjuvant and is widely used in a variety of vaccines. We developed a recombinant zoster vaccine (code: LZ901) consisting of a tetramer of VZV glycoprotein E (gE) and a human Fc fusion protein expressed in CHO cells, an immune complex-like molecule that can be adsorbed with an aluminum hydroxide adjuvant. We compared the immunogenicity of LZ901 with that of HZ/su in BALB/c mice. The results showed that LZ901 induced levels of gE-specific IgG antibodies comparable to those induced by HZ/su, and the results of FAMA titers further demonstrated their similar neutralizing antibody abilities. Most importantly, LZ901 induced higher levels of cell-mediated immunity (CMI) (which plays a decisive role in the efficacy of zoster vaccines) than HZ/su in BALB/c mice. The numbers of cytokine-producing T cells in LZ901-vaccinated mice were significantly greater than those in v-vaccinated mice, and the proportions of CD4+ and CD8+ T cells producing at least two types of cytokines in LZ901-vaccinated mice were significantly greater than those in HZ/su-vaccinated mice. [ABSTRACT FROM AUTHOR]

Recently updated COVID-19 mRNA vaccines encode the spike protein of the omicron subvariant XBB.1.5 and are recommended for patients with inflammatory bowel disease (IBD) on immunosuppressive treatment. Nonetheless, their immunogenicity in patients with IBD against rapidly expanding virus variants remains unknown. This prospective multicenter cohort study is the first study to investigate the immunogenicity of XBB.1.5-adapted vaccines in patients with IBD. Systemic and mucosal antibodies targeting the receptor-binding domains (RBDs) of the omicron subvariants XBB.1.5, EG.5.1, and BA.2.86, as well as their neutralization were quantified before and two to four weeks after vaccination with monovalent XBB.1.5-adapted mRNA vaccines. Vaccination increased levels of serum anti-RBD IgG targeting XBB.1.5, EG.5.1, and BA.2.86 (1.9-fold, 1.8-fold, and 2.6-fold, respectively) and enhanced corresponding neutralization responses (2.3-fold, 3.1-fold, and 3.5-fold, respectively). Following vaccination, anti-TNF-treated patients had reduced virus neutralization compared to patients on treatments with other cellular targets. 11.1% and 16.7% of patients lacked EG.5.1 and BA.2.86 neutralization, respectively; all these patients received anti-TNF treatment. At mucosal sites, vaccination induced variant-specific anti-RBD IgG but failed to induce RBD-targeting IgA. Our findings provide a basis for future vaccine recommendations while highlighting the importance of frequent booster vaccine adaptation and the need for mucosal vaccination strategies in patients with IBD. [ABSTRACT FROM AUTHOR]

The TAK-003 dengue vaccine was licensed in Europe in December 2022, and the official recommendations from most EU countries are still under formulation. To support policymakers, we performed a meta-analysis to quantify TAK-003's immunogenicity, efficacy and safety among seronegative and seropositive populations after the administration of one or two vaccine doses. We included trials retrieved from MEDLINE, Scopus and ClinicalTrials.gov. The outcomes were the rates of seroconversion, virologically confirmed dengue fever and serious adverse events after each vaccine dose. Data were combined using random-effect proportion or head-to-head meta-analyses. We retrieved a total of 19 datasets, including >20,000 participants. TAK-003 showed an excellent safety profile, and the immunogenicity after two doses against the four DENV serotypes was ≥90% among both adults and children/adolescents who were either seronegative or seropositive at baseline. A single dose was able to elicit a high immunogenic response among adults (≥70%) and children/adolescents (≥90%). The primary two-dose immunization course halved the risk of all types of virologically confirmed dengue fever among seropositive children/adolescents, but seronegative minors were only protected against the diseases caused by DENV-1 and DENV-2. Overall, the results support the use of TAK-003 for the prevention of dengue fever in the pediatric population of endemic countries. Uncertainties remain on the use of a single vaccine dose in non-endemic countries. [ABSTRACT FROM AUTHOR]

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use. [ABSTRACT FROM AUTHOR]

Introduction. Hepatitis B virus (HBV) vaccination has decreased the overall incidence of HBV infection; however, approximately 5 to 10% of people are non-responders to the vaccination. This study investigated the factors associated with non-response to HBV vaccination, with an emphasis on vitamin D deficiency (VDD). Methods. This retrospective observational study focused on adult workers in a single heavy industry. Individuals with negative initial hepatitis B surface antibody (anti-HBs) levels prior to vaccination and who then received a two- or three-dose series of HBV vaccinations were enrolled. The study endpoint was failure to achieve a seroprotective antibody response, defined as an anti-HBs titer less than 10 mIU/mL. Propensity score matching (PSM) and binary logistic regression models were used to adjust the outcomes for other clinical characteristics. Results. Among 760 workers, 566 (74.5%) exhibited VDD. The non-response rates to HBV vaccination were 13.4% (76/566) and 5.7% (11/194) among workers with and without VDD, respectively (p = 0.005). Even after adjustment using PSM, VDD was still associated with a higher rate of response failure (adjusted odds ratio 2.74; 95% confidence interval 1.40–5.38, p = 0.003). The binary logistic regression model showed that VDD, older age, omission of the third vaccine dose, lower initial anti-HBs titer, and current smoking were associated with response failure. Conclusions. Our study suggests that VDD may impair the serologic response following HBV vaccination. Further research is needed to evaluate the effectiveness of vitamin D supplementation in increasing the response to HBV vaccination. [ABSTRACT FROM AUTHOR]

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines. [ABSTRACT FROM AUTHOR]

Shiga toxin-producing Escherichia coli (STEC) poses a significant public health risk due to its zoonotic potential and association with severe human diseases, such as hemorrhagic colitis and hemolytic uremic syndrome. Ruminants are recognized as primary reservoirs for STEC, but swine also contribute to the epidemiology of this pathogen, highlighting the need for effective prevention strategies across species. Notably, a subgroup of STEC that produces Shiga toxin type 2e (Stx2e) causes edema disease (ED) in newborn piglets, economically affecting pig production. This study evaluates the immunogenicity of a chimeric protein-based vaccine candidate against STEC in pregnant sows and the subsequent transfer of immunity to their offspring. This vaccine candidate, which includes chimeric proteins displaying selected epitopes from the proteins Cah, OmpT, and Hes, was previously proven to be immunogenic in pregnant cows. Our analysis revealed a broad diversity of STEC serotypes within swine populations, with the cah and ompT genes being prevalent, validating them as suitable antigens for vaccine development. Although the hes gene was detected less frequently, the presence of at least one of these three genes in a significant proportion of STEC suggests the potential of this vaccine to target a wide range of strains. The vaccination of pregnant sows led to an increase in specific IgG and IgA antibodies against the chimeric proteins, indicating successful immunization. Additionally, our results demonstrated the effective passive transfer of maternal antibodies to piglets, providing them with immediate, albeit temporary, humoral immunity against STEC. These humoral responses demonstrate the immunogenicity of the vaccine candidate and are preliminary indicators of its potential efficacy. However, further research is needed to conclusively evaluate its impact on STEC colonization and shedding. This study highlights the potential of maternal vaccination to protect piglets from ED and contributes to the development of vaccination strategies to reduce the prevalence of STEC in various animal reservoirs. [ABSTRACT FROM AUTHOR]

Background: The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma—one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90–95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. Methods: Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. Results: A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). Discussion: A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine. [ABSTRACT FROM AUTHOR]

Bovine coronavirus (BCoV) is distributed globally and mainly causes different clinical manifestations: enteric diarrhea in calves, winter dysentery in adults, and respiratory symptoms in cattle of all ages. Low mortality and high morbidity are the hallmarks of BCoV infection, usually associated with substantial economic losses for the livestock industry. Vaccination, combined with the implementation of biosecurity measures, is the key strategy for the prevention of infections. This pilot study evaluates the immunogenicity of a recombinant vaccine containing two BCoV antigens (S and M) in sheep, compared to vaccines containing only the M or S protein. Three groups of sheep were inoculated intramuscularly at day 0 and day 21 with recombinant adenoviruses expressing BCoV S protein (AdV-BCoV-S), BCoV M protein (AdV-BCoV-M), or both proteins (AdV-BCoV-S + M). Serum antibodies were evaluated using immunofluorescence (IF) and serum neutralization (SN) tests. Moderate seroconversion was observed by day 21, but serum antibodies detected via SN increased from 1:27.5 (day 21) to 1:90 (day 28) in sheep inoculated with the recombinant AdV expressing both the S- and M-BCoV proteins. Based on the SN results, a repeated-measures ANOVA test indicated a more significant difference in immune response between the three groups (F = 20.47; p < 0.001). The experimental investigation produced satisfactory results, highlighting that the S + M recombinant vaccine was immunogenic, stimulating a valid immune response. Despite some inherent limitations, including a small sample size and the absence of challenge tests, the study demonstrated the efficacy of the immune response induced via the recombinant vaccine containing both S and M proteins compared to that induced via the individual proteins S or M. [ABSTRACT FROM AUTHOR]

Vandammella animalimorsus is a Gram-negative and non-motile bacterium typically transmitted to humans through direct contact with the saliva of infected animals, primarily through biting, scratches, or licks on fractured skin. The absence of a confirmed post-exposure treatment of V. animalimorsus bacterium highlights the imperative for developing an effective vaccine. We intended to determine potential vaccine candidates and paradigm a chimeric vaccine against V. animalimorsus by accessible public data analysis of the strain by utilizing reverse vaccinology. By subtractive genomics, five outer membranes were prioritized as potential vaccine candidates out of 2590 proteins. Based on the instability index and transmembrane helices, a multidrug transporter protein with locus ID A0A2A2AHJ4 was designated as a potential candidate for vaccine construct. Sixteen immunodominant epitopes were retrieved by utilizing the Immune Epitope Database. The epitope encodes the strong binding affinity, nonallergenic properties, non-toxicity, high antigenicity scores, and high solubility revealing the more appropriate vaccine construct. By utilizing appropriate linkers and adjuvants alongside a suitable adjuvant molecule, the epitopes were integrated into a chimeric vaccine to enhance immunogenicity, successfully eliciting both adaptive and innate immune responses. Moreover, the promising physicochemical features, the binding confirmation of the vaccine to the major innate immune receptor TLR-4, and molecular dynamics simulations of the designed vaccine have revealed the promising potential of the selected candidate. The integration of computational methods and omics data has demonstrated significant advantages in discovering novel vaccine targets and mitigating vaccine failure rates during clinical trials in recent years. [ABSTRACT FROM AUTHOR]