Vaccine Antigens Research Articles

Profile of Chlamydia vaccine research: A bibliometric analysis

ABSTRACT Vaccination is the most effective measure to prevent Chlamydia infection. However, to date, no vaccine has successfully completed the rigorous clinical trial process and gained regulatory approval for use in clinical practice. Scholars have been working on a safe and effective Chlamydia vaccine. In order to better grasp, the global frontiers and development trends in this field, a comprehensive bibliometric analysis was carried out. A total of 234 publications closely regarding Chlamydia vaccines were culled from the Web of Science Core Collection database, and the bibliometric information was then extracted with CiteSpace and VOSviewer software. After measurement analysis, the most influential papers were identified in this area, including highly cited papers, references with strong citation burst, and high co-citated papers. Vaccine has published the most literature on Chlamydia vaccines. Only scholars from 39 countries/regions have been engaged in studying Chlamydia vaccines. The USA is the most prolific country and has the highest collaborative strength. The current research area has focused on protective immunity and immunopathological response. Major outer membrane protein (MOMP) is the most common target vaccine antigen. This study reveals the status of literature and highlights emerging trends in this field, which helps researchers seek insights into this area and serve as a reference guide for further investigations.

PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies

ABSTRACT Circumsporozite protein (CSP), the most abundant surface protein in parasitic Plasmodium falciparum (Pf) sporozoite and an attractive target for malaria vaccine design, has been shown to induce protective humoral response in humans. In this work, we characterized and formulated a promising recombinant PfCSP immunogen (155) candidate consisting of two PfCSP epitopes (i.e. junction, NANP repeat) fused to H. pylori apoferritin forming a 24-mer nanoparticle. In addition, two N-linked glycans were engineered to mitigate possible anti-apoferritin immune responses, and a universal T-cell epitope was included to further enhance immunogenicity. Physicochemical characterization of the 155 antigen was performed including primary structure, post-translational modifications, conformational stability, and particle size. A competitive ELISA was developed to assess antigen binding to a PfCSP-specific mAb. The in vitro antigenicity of the 155 antigen was measured upon formulation with adjuvants, including aluminum-salts (i.e. AlhydrogelTM, Adju-PhosTM) and the TLR-9 agonist CpG 1018®, when freshly combined and after storage at different temperatures over 3 months. The in vivo immunological impact of various adjuvanted formulations of the 155 antigen was investigated in mice. The results support the formulation of 155 with AlhydrogelTM + CpG 1018® adjuvants as a promising recombinant malaria vaccine candidate from both a pharmaceutical and immunological perspective.

Diversifying T-cell responses: safeguarding against pandemic influenza with mosaic nucleoprotein.

The World Health Organization (WHO) estimates that seasonal influenza causes 3-5 million cases of severe illness annually. The influenza virus frequently undergoes genetic changes through antigenic drift and antigenic shift, resulting in annual epidemics and occasional pandemics. Consequently, a major public health objective is to develop a universal influenza vaccine that offers broad protection against both current and pandemic influenza A strains. In this study, we designed a nucleoprotein (NP) antigen (termed mosaic NP) comprising antigenic regions found in thousands of influenza viruses, aiming to use it as a vaccine to induce broad anti-influenza T-cell responses. Our findings indicate that the mosaic NP vaccine provided significant protection against seasonal H1N1 and H3N2, as well as the pandemic H1N1 strain, demonstrating its effectiveness across various influenza subtypes. These findings suggest that the mosaic NP is a potential universal influenza vaccine antigen, capable of protecting against diverse strains of influenza viruses.

Safety and immunogenicity of ascending doses of influenza A(H7N9) inactivated vaccine with or without MF59®.

While it remains impossible to predict the timing of the next influenza pandemic, novel avian influenza A viruses continue to be considered a significant threat. A Phase II study was conducted in healthy adults aged 18-64years to assess the safety and immunogenicity of two intramuscular doses of pre-pandemic 2017 influenza A(H7N9) inactivated vaccine administered 21days apart. Participants were randomized (n=105 in each of Arms 1-3) to receive 3.75μg, 7.5μg or 15μg of hemagglutinin (HA) with MF59® adjuvant, or 15μg of HA unadjuvanted vaccine (n=57, Arm 4). The three MF59 adjuvanted vaccines and the 15μg unadjuvanted vaccine were safe and well-tolerated. Little antibody activity was detected against the A(H7N9) vaccine antigen after the first vaccination across study Arms. After second vaccination, the three adjuvanted Arms showed increases in hemagglutination inhibition (HAI), neutralizing (Neut), and neuraminidase inhibition (NAI) geometric mean titers (GMT), peaking at 21days post second vaccination. The percentage of participants with titer ≥1:40 and seroconversion rates for HAI were 30-43% and 0 for the adjuvanted Arms and the unadjuvanted Arm, respectively. Antibody responses against antigenically drifted A(H7N9) strains A/Shanghai/2/2013 and A/Guangdong/17SF003/2016 showed similar trends. Exploratory linear modeling of HAI and Neut responses post second vaccination revealed significantly lower log antibody titers among older participants (aged 35-49 and 50-64years) compared to participants aged 18-34years after adjusting for study vaccination, BMI, sex, and prior seasonal influenza vaccination. Post second vaccination, participants who received seasonal influenza vaccination in at least one of the two previous seasons had significantly lower log antibody titers than participants who did not. Adjuvanted doses of vaccine provided higher antibody responses, on average, than the 15μg unadjuvanted vaccine. Proportion of participants achieving seroconversion and antibody titers ≥40 remained below 50% in all study Arm.

A-910823, a squalene-based emulsion adjuvant, enhances robust and broad immune responses of quadrivalent influenza vaccine in ferrets.

Robust and broad protective immunity is typically elicited by co-administration of an adjuvant with vaccine antigens. A-910823, a squalene-based emulsion adjuvant, has been approved in Japan. It effectively enhances the humoral and cellular immunity of S-268019-b, a recombinant COVID-19 vaccine; however, the adjuvant effects of A-910823 on other vaccines, including influenza vaccine, have not been evaluated. Here, a ferret model was employed to investigate the adjuvant effects of A-910823 when combined with split-inactivated quadrivalent influenza vaccine (QIV). We demonstrate that combination of A-910823 with QIV enhances the neutralizing antibody titer and its breadth against non-vaccine strains. Also, the protective efficacy of A-910823-adjuvanted QIV against virus challenge has been confirmed. Of note, QIV combined with A-910823 caused only minor detectable side effects, whereas a significant increase in fever was observed after two doses of mRNA-LNP in ferrets. This study provides information on the effectiveness and safety of A-910823-adjuvanted QIV and suggests the usefulness of the ferret model for evaluating vaccine-induced reactogenicity.

Comment on Kerro Dego et al. Evaluation of Streptococcus uberis Surface Proteins as Vaccine Antigens to Control S. uberis Mastitis in Dairy Cows. Vaccines 2021, 9, 868

A recent publication by Kerro Dego et al [...]

Fusion protein-based COVID-19 vaccines exemplified by a chimeric vaccine based on a single fusion protein (W-PreS-O)

In this article we discuss characteristics of fusion protein-based SARS-CoV-2 vaccines. We focus on recombinant vaccine antigens comprising fusion proteins consisting of combinations of SARS-CoV-2-derived antigens or peptides or combinations of SARS-CoV-2 antigens/peptides with SARS-CoV-2-unrelated proteins/peptides. These fusion proteins are made to increase the immunogenicity of the vaccine antigens and/or to enable special targeting of the immune system. The protein-based vaccine approach is exemplified solely in a proof of concept study by using W-PreS-O, a chimeric vaccine based on a single fusion protein (W-PreS-O), combining RBDs from Wuhan hu-1 wild-type and Omicron BA.1 with the hepatitis B virus (HBV)-derived PreS surface antigen adsorbed to aluminum hydroxide. The W-PreS-O vaccine was evaluated in Syrian hamsters which were immunized three times at three-week intervals with W-PreS-O or with aluminum hydroxide (placebo) before they were infected with Omicron BA.1. Neutralizing antibody (nAB) titers, weight, lung symptoms, and viral loads, as measured using RT-PCR in the upper and lower respiratory tracts, were determined. In addition, infectious virus titers from the lungs were measured using a plaque-forming assay. We found that W-PreS-O-vaccinated hamsters developed robust nABs against Omicron BA.1, showed almost no development of pneumonia, and had significantly reduced infectious virus titers in the lungs. Importantly, the viral loads in the nasal cavities of W-PreS-O-vaccinated hamsters were close to or above the PCR cycle threshold considered to be non-infectious. The data of our proof-of-concept study provides compelling evidence that the W-PreS-O vaccine has protective effect against Omicron BA.1 in a Syrian hamster in vivo infection model and thus support the promising results obtained also for other fusion protein-based SARS-CoV-2 vaccines.

Combination adjuvant improves influenza virus immunity by downregulation of immune homeostasis genes in lymphocytes.

Adjuvants play a central role in enhancing the immunogenicity of otherwise poorly immunogenic vaccine antigens. Combining adjuvants has the potential to enhance vaccine immunogenicity compared with single adjuvants, although the cellular and molecular mechanisms of combination adjuvants are not well understood. Using the influenza virus hemagglutinin H5 antigen, we define the immunological landscape of combining CpG and MPLA (TLR-9 and TLR-4 agonists, respectively) with a squalene nanoemulsion (AddaVax) using immunologic and transcriptomic profiling. Mice immunized and boosted with recombinant H5 in AddaVax, CpG+MPLA, or AddaVax plus CpG+MPLA (IVAX-1) produced comparable levels of neutralizing antibodies and were equally well protected against the H5N1 challenge. However, after challenge with H5N1 virus, H5/IVAX-1-immunized mice had 100- to 300-fold lower virus lung titers than mice receiving H5 in AddaVax or CpG+MPLA separately. Consistent with enhanced viral clearance, unsupervised expression analysis of draining lymph node cells revealed the combination adjuvant IVAX-1 significantly downregulated immune homeostasis genes, and induced higher numbers of antibody-producing plasmablasts than either AddaVax or CpG+MPLA. IVAX-1 was also more effective after single-dose administration than either AddaVax or CpG+MPLA. These data reveal a novel molecular framework for understanding the mechanisms of combination adjuvants, such as IVAX-1, and highlight their potential for the development of more effective vaccines against respiratory viruses.

Reverse vaccinology: A strategy also used for identifying potential vaccine antigens in poultry.

Vaccination of livestock plays a major role in improving animal health, welfare and productivity, but also in public health by preventing zoonotic diseases. Advances in bioinformatics and whole-genome sequencing techniques since the 2000s have led to the development of genome-based vaccinology, called reverse vaccinology. Reverse vaccinology is a rapid and competitive strategy that uses pathogen genome sequences to screen for and identify potential vaccine antigens and, unlike conventional methods, does not require culturing the pathogenic microorganism, at least initially. Based on in silico approaches and dedicated software, reverse vaccinology has led to the identification of a wide range of proteins as putative vaccine candidates against human pathogens and has been applied more recently to several animal diseases. After a brief overview of the principle of the approach and its applications in human medicine, this review focuses on the use of reverse vaccinology for the development of vaccines specifically for poultry, a representative example of livestock vaccination, and discusses the important points to consider when using this method.

In silico design of an epitope-based vaccine ensemble for fasliolopsiasis.

Fasciolopsiasis, a food-borne intestinal disease is most common in Asia and the Indian subcontinent. Pigs are the reservoir host, and fasciolopsiasis is most widespread in locations where pigs are reared and aquatic plants are widely consumed. Human infection has been most commonly documented in China, Bangladesh, Southeast Asia, and parts of India. It predominates in school-age children, and significant worm burdens are not uncommon. The causal organism is Fasciolopsis buski, a giant intestinal fluke that infects humans and causes diarrhoea, fever, ascites, and intestinal blockage. The increasing prevalence of medication resistance and the necessity for an effective vaccination make controlling these diseases challenging. Over the last decade, we have achieved major advances in our understanding of intestinal fluke biology by in-depth interrogation and analysis of evolving F. buski omics datasets. The creation of large omics datasets for F. buski by our group has accelerated the discovery of key molecules involved in intestinal fluke biology, toxicity, and virulence that can be targeted for vaccine development. Finding successful vaccination antigen combinations from these huge number of genes/proteins in the available omics datasets is the key in combating these neglected tropical diseases. In the present study, we developed an in silico workflow to select antigens for composing a chimeric vaccine, which could be a significant technique for developing a fasciolopsiasis vaccine that prevents the parasite from causing serious harm. This chimeric vaccine can now be tested experimentally and compared to other vaccine candidates to determine its potential influence on human health. Although the results are encouraging, additional validation is needed both in vivo and in vitro. Considering the extensive genetic data available for intestinal flukes that has expanded with technological advancements, we may need to reassess our methods and suggest a more sophisticated technique in the future for identifying vaccine molecules.

The Generation of a H9N2 Avian Influenza Virus with HA and C3d-P29 Protein Fusions and Vaccine Development Applications

Background: Maternal-derived antibody (MDA) interferes with immune responses, leading to the failure of H9N2 avian influenza vaccinations in poultry. So far, none of the commercially available H9N2 avian influenza vaccines used in poultry have been able to overcome MDA interference. Methods: To develop a vaccine that can overcome MDA interference, one or multiple copies of the minimum-binding domain (P29) from the complement protein C3d were inserted in between the signal peptide and the head domain of the hemagglutinin (HA) protein on a H9N2 avian influenza virus (A/Chicken/Shanghai/H514/2017, named H514). Results: The HA proteins containing P29 stimulated stronger type I interferences than wild-type HA proteins in vitro. The modified viruses with the HA proteins containing one copy of P29 (rH514-P29.1) and two copies of P29.2 (rH514-P29.2) were successfully rescued using reverse genetics. The inactivated vaccines developed with rH514-P29.1 or rH514-P29.2 induced higher and faster humoral immune responses than the vaccine developed with rH514 in specific pathogen-free (SPF) chickens. To evaluate the vaccines’ efficacy in the presence of MDA and to ensure a uniform level of MDA, passively transferred antibody (PTA) was used as a model to mimic MDA in 1-day-old SPF chickens. Our results showed that the rH514-P29.2 inactivated vaccine induced significantly higher HI titers than the rH514 inactivated vaccine in the presence of PTA. More importantly, it reduced viral shedding after being challenged with H514 in the presence of PTA. Conclusions: Our results suggest that vaccine antigens fused with two copies of P29 can decrease the interference of MDA on immunity in chickens. Overall, our results provide a new strategy for overcoming MDA interference.

Wall teichoic acid glycosylation of bovine-associated Staphylococcus aureus strains.

Staphylococcus aureus (S. aureus) is one of the major causes of bovine mastitis, a disease with detrimental effects on health and wellbeing. Current control measures are costly, laborious and not always effective in eradicating S. aureus. The cell wall-linked polysaccharide wall teichoic acid (WTA) is highly immunogenic in humans and is considered as a prospective vaccine antigen based on promising pre-clinical studies in animals. WTA consist of polymerized ribitol-phosphate backbone that is modified with N-acetylglucosamine (GlcNAc) moieties in different configurations by the glycosyltransferases TarS (β-1,4-GlcNAc), TarM (α-1,4-GlcNAc) and TarP (β-1,3-GlcNAc). This study aimed to characterize the presence and genetic variation in tarS, tarM and tarP in bovine-associated S. aureus strains and how this impacts WTA-glycoprofile. Bioinformatic analyses of a whole genome sequence database consisting of 1047 S. aureus, 10 S. schweitzeri, and 6 S. argenteus strains showed that over 99% of strains contained tarS, 34 % also contained tarM, while 5 % of the strains encoded tarP in addition to tarS. The distribution of WTA-glycosyltransferase genes was similar to what has been reported for human-associated S. aureus strains. Phenotypic analysis of WTA glycosylation by flow cytometry corroborated with tarS/tarM/tarP gene presence. The WTA glycoprofile was variable between bovine-associated strains and the levels and ratios of GlcNAcylation were affected by growth conditions. Interestingly, a divergent tarM allele was present in strains of clonal complexes (CC) 49 and the mastitis-associated CC151, but its function was similar to canonical tarM. In conclusion, we demonstrated that bovine-associated S. aureus strains show similar variation in WTA GlcNAc decoration as human S. aureus strains, despite the presence of a divergent tarM allele.

Negative Association of Gulf War Illness Symptomatology with Predicted Binding Affinity of Anthrax Vaccine Antigen to Human Leukocyte (HLA) Class II Molecules.

Anthrax is a serious disease caused by Bacillus anthracis (B. anthracis) with a very high mortality when the spores of B. anthracis are inhaled (inhalational anthrax). Aerosolized B. anthracis spores can be used as a deadly bioweapon. Vaccination against anthrax is the only effective preventive measure and, hence, the anthrax vaccine was administered to United States (and other) troops during the 1990-91 Gulf War. However, the anthrax vaccine is not harmless, and the anthrax vaccination has been linked to the occurrence and severity of Gulf War Illness (GWI), a debilitating Chronic Multisymptom Illness (CMI). We hypothesized that this is partly due to the combination of two factors, namely (a) the cytotoxicity of the antigen (anthrax Protective Antigen, PA) contained in the vaccine, and (b) the Human Leukocyte Antigen (HLA) genotype of susceptible vaccinees, reducing their ability to make antibodies against the cytotoxic PA. Here, we tested this hypothesis by determining the association between severity of GWI symptoms in 458 GW veterans and the overall strength of the binding affinity of the PA epitopes to the specific six Human Leukocyte Antigen (HLA) Class II alleles carried by each individual (two of each of the HLA-II genes: DPB1, DQB1, DRB1), responsible for initiating the process of antibody production in otherwise immunocompetent individuals, estimated in silico. We found that the severity of GWI symptomatology was negatively and significantly correlated with the strength of the predicted binding affinity of PA peptides to HLA-II molecules (r=-0.356, p<0.001); the stronger the overall binding affinity, the weaker the symptoms. Since the binding of a peptide to an HLA-II molecule is the first and necessary step in initiating the production of antibodies, the findings above support our hypothesis that the severity of GWI symptomatology is partly due to a lack of HLA-II protection. Reduced HLA protection against the toxic anthrax vaccine may underlie GWI.

Antibody responses against influenza A decline with successive years of annual influenza vaccination

Influenza vaccine effectiveness and immunogenicity can be compromised with repeated vaccination. We assessed immunological markers in a cohort of healthcare workers (HCW) from six public hospitals around Australia during 2020–2021. Sera were collected pre-vaccination and ~14 and ~180 days post-vaccination and assessed in haemagglutination inhibition assay against egg-grown vaccine and equivalent cell-grown viruses. Responses to vaccination were compared by the number of prior vaccinations. Baseline sera were available for 595 HCW in 2020 and 1031 in 2021. 5% had not been vaccinated during five years prior to enrolment and 55% had been vaccinated every year. Post-vaccination titres for all vaccine antigens were lowest among HCW vaccinated in all 5-prior years and highest among HCW with 0 or 1 prior vaccinations, even after adjustment. This was observed for both influenza A subtypes and was dependent on pre-vaccination titre. Expanded cohorts are needed to better understand how this translates to vaccine effectiveness.

Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae

Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. However, it exhibits high levels of antigenic variability, posing a significant obstacle in evoking a broadly protective immune response. Here, we utilize phylogenetic information to rationally select TbpB variants for inclusion into a gonococcal vaccine and identify two TbpB variants that together elicit a highly cross-reactive antibody response against a diverse panel of TbpB variants and clinically relevant gonococcal strains. This formulation performed well in experimental proxies of real-world usage, including eliciting bactericidal activity against diverse gonococcal strains and decreasing the median duration of colonization after vaginal infection in female mice. These data support the use of a combination of TbpB variants for a broadly protective gonococcal vaccine.

MIP-3α-antigen fusion DNA vaccine enhances sex differences in tuberculosis model and alters dendritic cell activity early post vaccination.

Background Tuberculosis (TB) remains a major cause of global morbidity and mortality. Efforts to control TB are hampered by the lengthy and cumbersome treatment required to eradicate the infection. Bacterial persistence during exposure to bactericidal antibiotics is at least partially mediated by the bacterial stringent response enzyme, Rel Mtb . A therapeutic DNA vaccine targeting Rel Mtb has been shown to increase the efficacy of antitubercular drugs, and fusing macrophage-inflammatory protein 3α (MIP-3α), which interacts with CCR6 on immature dendritic cells (iDCs), to Rel Mtb further increases the vaccine's therapeutic efficacy. A secondary analysis of these prior studies elucidated prominent sex-based differences in vaccine therapeutic efficacy, with female mice showing improved microbial outcomes compared to males as a result of the Rel and MIP-3α-Rel vaccine constructs, with a greater sex-associated difference in the MIP-3α-Rel group. In the current study, we addressed the hypothesis that these sex-related differences are due to differential DC activation/function soon after vaccination. Methods A EαGFP reporter vaccine model was used to track vaccine antigen presentation by an antibody Y-Ae which binds the Eα peptide tag in complex with I-A b MHC-II molecules. Results MIP-3α-EαGFP groups had more DCs presenting vaccine antigen infiltrating from the periphery, with more abundant Langerhans cells in males and greater CD8 + CD103 + cross-presenting dermal DCs in females. This model also shows there is greater DC activation, as measured by CD80 and MHC II MFI, by MIP-3α compared to EαGFP alone, especially in female mice. Conclusions Our findings are consistent with the sex- and MIP-3α-related differences seen in the therapeutic model and supports the hypothesis that in both sexes MIP-3α enhances vaccine uptake and cell activation by peripheral iDCs. Additionally, Female mice showed greater levels of antigen presentation, especially in DCs able to cross-present antigen, explaining why they had the best outcomes. Further studies are required to understand underlying mechanisms and to link APC results directly to T-cell responses.

Protective potential of structural proteins of the SARS-CoV-2 virus in protecting against COVID-19

Introduction. Many different vaccines for the prevention of COVID-19 have received emergency use approval in the shortest possible time. Due to the high rate of variability of the pathogen, in this study we analyzed the variability of the structural proteins of the SARS-CoV-2 virus and compared their protective potential in protecting animals from COVID-19. The aim of the study was to compare the protective potential of the SARS-CoV-2 structural proteins in protecting animals from COVID-19. Materials and methods. The SARS-CoV-2 virus was used in the study. Transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/J (F1) were used as model animals. Recombinant adenoviral vectors rAd5-S, rAd5-N, rAd5-M were used for immunization of animals. Various genetic, virological and immunological methods, as well as methods of working with animals, were used in the study. Results. The largest number of amino acid substitutions in the structural proteins of different SARS-CoV-2 variants was detected in glycoprotein S, the smallest — in nucleoprotein N. In the COVID-19 animal model, it was shown that only the use of glycoprotein S as a vaccine antigen allows to form protective immunity that protects 100% of animals from a lethal infection caused by the SARS-CoV-2 virus, while the use of protein N protects 50% of animals from a lethal infection, and protein M does not have a protective potential. Conclusion. The data obtained, as well as the analysis of the epidemiological efficacy of various mRNA and vector vaccines, demonstrate that the use of the SARS-CoV-2 glycoprotein S as an antigen allows to form the highest level of protection. Due to the constant change in circulating variants of the SARS-CoV-2 virus, the decrease in the effectiveness of the vaccines with the original antigen composition against new variants of the virus and the continuing high incidence of COVID-19, it is necessary to continuously monitor the effectiveness of vaccines against new variants of the virus and promptly update the antigen composition of vaccines when a decrease in effectiveness is detected.

Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness.

We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness. In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections. Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections. When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.

Neutralization of omicron subvariants and antigenic cartography following multiple COVID 19 vaccinations and repeated omicron non JN.1 or JN.1 infections

The ongoing emergence of SARS-CoV-2 variants, combined with antigen exposures from different waves and vaccinations, poses challenges in updating COVID-19 vaccine antigens. We collected 206 sera from individuals with vaccination-only, hybrid immunity, and single or repeated omicron post-vaccination infections (PVIs), including non-JN.1 and JN.1, and evaluated neutralization against omicron BA.5, BA.2.75, BQ.1.1, XBB.1.16, XBB.1.5, and JN.1. Neutralizing antibodies exhibited a narrow breadth against BA.5 and BA.2.75 and failed to neutralize BQ.1.1 and XBB lineages after three to five doses of the ancestral monovalent vaccine. Hybrid immunity elicited higher neutralizing titers than vaccination alone, but titers remained relatively low. A single omicron PVI elicited lower neutralization titers to all variants compared to wild-type (WT), indicating immunological imprinting. Repeated omicron PVIs, particularly JN.1, slightly mitigated these effects by increasing broad neutralization responses to all variants, though not significantly. Antigenic mapping demonstrated that XBB lineages and JN.1 are antigenically distant from WT and also evaded antibodies induced by earlier omicron variants (BA.1–5) PVIs. However, repeated JN.1 PVIs shortened this antigenic distance, indicating broader neutralization across omicron variants. These findings highlight SARS-CoV-2 immunity following various antigen boosts and the impact of repeated omicron JN.1 exposure on broad immunity, informing future COVID-19 vaccination strategies.

VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens.

VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient's private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL's somatic mutations and human polymorphisms remain unexplored. To study these immunogens, we performed whole-exome sequencing of paired tumor and germinal samples from four vaccinated patients and the vaccine cells. VACCIMEL variants were called by comparing the vaccine and the patient's exomes, and non-synonymous coding variants were used to predict T cell epitopes. Candidates were ranked based on their mRNA expression in VACCIMEL, predicted peptide-HLA (pHLA) presentation, and pHLA stability. Then, the immune responses to prioritized epitope candidates were tested using IFNγ ELISpot assays on vaccinated patients' PBMC samples. The comparison of the vaccine with the patients' germinal exomes revealed on average 9481 coding non-synonymous variants, suggesting that VACCIMEL offers a high number of potential antigens. Between 0,05 and 0,2% of these variants were also found in the tumors of three vaccinated patients; however, one patient with a high tumor mutational burden (TMB) shared 19,5% somatic variants. The assessment of T cell responses showed that vaccinated patients mounted highly diverse responses against VACCIMEL peptides. Notably, effector T cells targeting the patient's tumor antigens, comprising neoantigens and TAA, were found in higher frequencies than T cells targeting VACCIMEL-exclusive antigens. On the other hand, we observed that the immunogenic epitopes are not conserved across patients, despite sharing HLA and that immune responses fluctuate over time. Finally, a positive correlation between VACCIMEL antigen expression and the intensity of the T cell responses was found. Our results demonstrate that the immune system simultaneously responds to a high number of antigens, either vaccinal or private, proving that immune responses against epitopes not expressed in the patient's tumors were not detrimental to the immune recognition of neoantigens and TAA.