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Introduction: Both cellular and humoral responses are important for vaccine protection, but recommendations on immunosuppressants in dermatology are largely based on pre-pandemic experiences. This study aimed to investigate the impacts of immunosuppressants on humoral and cellular immunogenicity to COVID-19 vaccinations in pemphigus patients. Methods: SARS-CoV-2-naïve pemphigus patients and age-, and sex-matched healthy controls were recruited from multiple tertiary medical centers during 2021-2023. Anti-spike protein-related T-cell responses, antibody titers, and high-parameter cell analysis of the peripheral blood were utilized to investigate the inhibitory effects of immunosuppressants, including rituximab and azathioprine. Results: A total of 32 patients and 120 healthy controls were enrolled. COVID-19 vaccinations spaced at least six months after the last rituximab infusion did not cause a significant difference in anti-viral T-cell or antibody responses between rituximab-naïve and rituximab-treated patients. All pemphigus patients demonstrated improved antibody responses after the third vaccination and none of them suffered from severe COVID-19 illness. Intriguingly, we found that daily dosages of 100 mg or more of azathioprine were linked to significantly decreased anti-viral T-cell responses induced by the vaccination (mean of fold change [SD]; higher azathioprine dosage = 0.70 [0.61] folds vs. lower azathioprine dosage = 2.11 [1.03] folds; p = 0.044). Conclusion: Except for a subset of patients with unrecovered B-cell deficiency, rituximab infusion with proper scheduling of vaccination preserved better anti-viral T-cell responses and did not lead to hindered antibody responses in pemphigus patients. All pemphigus patients benefited from receiving the third booster regardless of B-cell status. [ABSTRACT FROM AUTHOR]

Glycopeptides derived from the glycoprotein mucin‐1 (MUC1) have shown potential as tumor‐associated antigens for cancer vaccine development. However, their low immunogenicity and non‐selective conjugation to carriers present significant challenges for the clinical efficacy of MUC1‐based vaccines. Here, we introduce a novel vaccine candidate based on a structure‐guided design of an artificial antigen derived from MUC1 glycopeptide. This engineered antigen contains two non‐natural amino acids and has an α‐S‐glycosidic bond, where sulfur replaces the conventional oxygen atom linking the peptide backbone to the sugar N‐acetylgalactosamine. The glycopeptide is then specifically conjugated to the immunogenic protein carrier CRM197 (Cross‐Reactive Material 197), a protein approved for human use. Conjugation involves selective reduction and re‐bridging of a disulfide in CRM197, allowing the attachment of a single copy of MUC1. This strategy results in a chemically defined vaccine while maintaining both the structural integrity and immunogenicity of the protein carrier. The vaccine elicits a robust Th1‐like immune response in mice and generates antibodies capable of recognizing human cancer cells expressing tumor‐associated MUC1. When tested in mouse models of colon adenocarcinoma and pancreatic cancer, the vaccine is effective both as a prophylactic and therapeutic use, significantly delaying tumor growth. In therapeutic applications, improved outcomes were observed when the vaccine was combined with an anti‐programmed cell death protein 1 (anti‐PD‐1) checkpoint inhibitor. Our strategy reduces batch‐to‐batch variability and enhances both immunogenicity and therapeutic potential. This site‐specific approach disputes a prevailing dogma where glycoconjugate vaccines require multivalent display of antigens. [ABSTRACT FROM AUTHOR]

Objectives: To analyse the general and primary outcome‐related characteristics of clinical trials protocols on COVID‐19 vaccines. Study Design and Setting: A meta‐research study. A search for clinical trial protocols on COVID‐19 vaccines was conducted on the ClinicalTrials.gov platform. We considered all protocols of comparative trials registered up to October 26, 2021. Results: Two hundred and eighty‐two trials were analysed. The median expected trial duration was 445 days (interquartile range [IQR] = 225), and the median target sample size was 420 participants (IQR = 1638). A retrospective registry (after the start date) was observed for 42.55% of the trials. Randomization procedures were planned by 84.75% and full‐blinding procedures by 34.75% of the 282 trials. Most trials were labelled as active or still recruiting, and 14 trials (5%) were completed. None of the 14 trials labelled as completed on our search date had results available. Industry funding was reported by 198 trials (70.2%). Most studies declared more than one primary outcome, usually a safety or immunogenicity outcome, and 59 studies (20.9%) had at least one primary efficacy outcome. The description of the primary efficacy outcomes was limited in most cases, referred to as a non‐specified 'efficacy' outcome (18.6%) or described as 'COVID‐19 cases' (32.2%). Conclusion: the primary outcomes of clinical trials on COVID‐19 vaccines are poorly described, and the registers provide insufficient information about them. The registry was retrospectively fulfilled for many trials, which may lead to bias and research waste. Outcomes were generically described and did not provide transparent information for replication in practice, further trials or meta‐analyses. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC). Methods: Open-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study. Results: 125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p <0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p <0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups. Conclusion: 4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status. [ABSTRACT FROM AUTHOR]

Obesity is a recognized factor influencing immune function and infectious disease outcomes. Characterization of the influence of obesity on SARS-CoV-2 humoral vaccine immunogenicity is required to properly tailor vaccine type (mRNA, viral-vector, protein subunit vaccines) and dosing schedule. Data from a prospective cohort study collected over 34 months was used to evaluate the slope of antibody production and decay and neutralizing capacity following SARS-CoV-2 vaccination in individuals with and without obesity at baseline. Most participants were female (65.4%), white (92.4%), and received mRNA vaccines. 210 were obese and 697 non-obese. Sex and infection-acquired immunity were identified as effect modifiers for the relationship between obesity and COVID-19 vaccine humoral immunogenicity. No consistent influence of obesity on peak titres, titre retention, antibody isotype (IgG, IgM, IgA), or neutralization was identified when controlling for other key variables. It may not be necessary to consider this variable when developing SARS-CoV-2 vaccine dosing strategies. [ABSTRACT FROM AUTHOR]

Background: Classical Swine Fever (CSF) is still one of the most economically important viral diseases of pigs. In endemic countries, the disease is controlled mostly through vaccination; hence, the availability of safe and effective vaccines is of utmost importance. Vaccines intended for application in developing countries must also be thermally stable, since the infrastructure needed to maintain a cold chain in those countries is usually lacking. Porvac® is a second-generation subunit marker vaccine against CSF that has demonstrates to be safe and protective. Previous studies have also shown that the vaccine is stable for 1 week at 37 oC and have a shelf life of at least 36 months at 2–8 oC. The aim of this work was to further explore the accelerated stability of Porvac® by assessing the physicochemical properties of the emulsion, and the safety and immunogenicity of the vaccine subjected to more drastic conditions of thermal stress: (1) 25 oC for 12 months; (2) 30oC and 37 oC for one month and (3) 15 days at 37 °C after the cap of the vials had been needle-punctured. Results: The vaccine subjected to all these conditions did not show significant changes in the physicochemical properties of the emulsion; did not produce local or systemic adverse reactions in pigs, and the chromatographic profile of the recovered antigen was preserved. All vaccinated swine developed neutralizing antibody titers ≥ 1:1000 at 28 days post vaccination. Conclusions: Porvac® is stable in all the experimental conditions tested, even after cap puncture, and retains the capacity to induce high titers of neutralizing antibodies, well above the threshold of protection. These results reinforce the robustness of the vaccine, and support its use as a very attractive alternative to modified live vaccines in developing countries endemic for CSF. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii, a common nosocomial pathogen, is known for its rapid acquisition of antimicrobial resistance, underscoring the urgent need to develop an effective vaccine against this pathogen. Outer membrane protein 22 (Omp22) regulates the biogenesis of outer membrane vesicles to transport virulence-promoting factors into the host cells and facilitates the progression of A. baumannii infection. In this study, we used a mouse model to assess a vaccine's immunogenicity and protective efficacy using recombinant Omp22 protein within the hypervariable region of flagellin (FliC-Omp22). FliC-Omp22 demonstrated superior protection following challenge with a lethal dose of multidrug-resistant (MDR) A. baumannii strain 58ST compared to Omp22 alone. In addition, it elicited increased IgG1/IgG2a and IL-4/IFN-γ ratios, indicating a predominant Th2 immune response. Furthermore, the FliC-Omp22 vaccination elicited strong specific antibodies that inhibited the adhesion and invasion of A. baumannii 58ST and enhanced the opsonic killing activity against the pathogen. FliC-Omp22 immunization significantly reduced bacterial loads in infected mice's spleen, lungs, and liver, thereby improving their survival against the lethal infection caused by MDR A. baumannii 58ST. This study suggests that integrating Omp22 into the hypervariable domain of flagellin holds promise for developing an effective vaccine against A. baumannii infections. [ABSTRACT FROM AUTHOR]

Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models. The method is applied to two datasets from immunogenicity sub-studies of vaccine phase 3 clinical trials for zoster and dengue vaccines. Results show that using immunogenicity-based estimation of efficacy in subgroups using time-to-event models is more precise than the standard estimation. Incorporating immune correlate data in time-to-event models improves precision in estimating efficacy (i.e., yields narrower confidence intervals), which can assist vaccine developers and public health authorities in making informed decisions. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the seroconversion rate and percent inhibition of neutralizing antibodies against the wild-type and Omicron variants of SARS-CoV-2 in patients with solid cancer who received two COVID-19 vaccine doses by comparing chemotherapy and nonchemotherapy groups. Methods: This prospective cohort study enrolled 115 cancer patients from Maharaj Nakorn Chiang Mai Hospital, Sriphat Medical Center, Faculty of Medicine, Chiang Mai University, and Chiang Mai Klaimor Hospital, Chiang Mai, Thailand, between August 2021 and February 2022, with data from 91 patients who received two COVID-19 vaccine doses analyzed. Participants received vaccines as part of their personal vaccination programs, including various mRNA and non-mRNA vaccine combinations. Blood samples were collected at baseline, on day 28, and at 6 months post-second dose to assess neutralizing antibodies. The primary outcome was the seroconversion rate against the wild-type and Omicron variants on day 28. Secondary outcomes included seroconversion at 6 months, factors associated with seroconversion, and safety. Results: Among the participants, 45% were receiving chemotherapy. On day 28, seroconversion rates were 77% and 62% for the wild-type and Omicron variants, respectively. Chemotherapy did not significantly affect seroconversion rates (p = 0.789 for wild type, p = 0.597 for Omicron). The vaccine type administered was positively correlated with seroconversion, with an adjusted odds ratio (95% confidence interval) of 25.86 (1.39–478.06) for the wild type and 17.38 (3.65–82.66) for the Omicron variant with the primary heterologous vaccine regimen. Grades 1 and 2 adverse events were observed in 34.0% and 19.7% of participants, respectively. Conclusions: Despite the lower seroconversion rate against the Omicron variant, no significant difference was observed between the chemotherapy and nonchemotherapy groups. COVID-19 vaccinations demonstrated good tolerability in this cohort. These findings highlight the importance of vaccine safety and immunogenicity in cancer patients and can inform tailored vaccination strategies for this vulnerable population. [ABSTRACT FROM AUTHOR]

Objectives: SARS-CoV-2 caused the COVID-19 pandemic, which overwhelmed global healthcare systems. Over 776 million COVID-19 cases and more than 7 million deaths were reported by WHO in September 2024. COVID-19 vaccination is crucial for preventing infection and controlling the pandemic. Here, we describe the design and development of a next-generation multi-epitope vaccine for SARS-CoV-2, consisting of T cell epitopes. Methods: Immunoinformatic methods were used to derive models for the selection of MHC binders specific for the mouse strain used in this study among a set of human SARS-CoV-2 T cell epitopes identified in convalescent patients with COVID-19. The immunogenicity of the vaccine prototype was tested on humanized-ACE2 transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J mice by in vitro, in vivo, and ex vivo immunoassays. Results: Eleven binders (two from the Envelope (E) protein; two from the Membrane (M) protein; three from the Spike (S) protein; and four from the Nucleocapsid (N) protein) were synthesized and included in a multi-epitope vaccine prototype. The animals were immunized with a mix of predicted MHC-I, MHC-II, or MHC-I/MHC-II peptide epitopes in Complete Freund's Adjuvant, and boosted with peptides in Incomplete Freund's Adjuvant. Immunization with SARS-CoV-2 epitopes remodeled the lymphocyte profile. A weak humoral response and the significant production of IL-4 and IFN-γ from T cells were found after the vaccination of the animals. Conclusions: The multi-epitope vaccine prototype presented in this study demonstrates immunogenicity in mice and shows potential for human vaccine construction. [ABSTRACT FROM AUTHOR]

The safety of casirivimab + imdevimab (CAS + IMD) (anti-severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] monoclonal antibodies [mAbs]) in pediatric outpatients with coronavirus disease 2019 (COVID-19) was evaluated in a randomized phase 1/2/3 trial. Consistent with adults, CAS + IMD was generally well tolerated with low drug-induced immunogenicity rates. The findings support the development of next-generation anti-SARS-CoV-2 mAbs for at-risk pediatric patients. [ABSTRACT FROM AUTHOR]

Despite the great potential of DNA vaccines for a broad range of applications, ranging from prevention of infections, over treatment of autoimmune and allergic diseases to cancer immunotherapies, the implementation of such therapies for clinical treatment is far behind the expectations up to now. The main reason is the poor immunogenicity of DNA vaccines in humans. Consequently, the improvement of the performance of DNA vaccines in vivo is required. This mini‐review provides an overview of the current state of DNA vaccines and the various strategies to enhance the immunogenic potential of DNA vaccines, including (i) the optimization of the DNA construct itself regarding size, nuclear transfer and transcriptional regulation; (ii) the use of appropriate adjuvants; and (iii) improved delivery, for example, by careful choice of the administration route, physical methods such as electroporation and nanomaterials that may allow cell type‐specific targeting. Moreover, combining nanoformulated DNA vaccines with other immunotherapies and prime‐boost strategies may help to enhance success of treatment. [ABSTRACT FROM AUTHOR]

Fasciolosis is a parasitosis of great importance for livestock, as well as for public health, as it is considered by the WHO as a neglected disease. Disease control is complex and reinfections make the use of therapeutic products an unsustainable method from an economic, environmental and health point of view. The aim of this study was to evaluate a new vaccine formulation for dairy cattle, containing soluble Fasciola hepatica antigens associated with Montanide 763 AVG and saponin adjuvants (FhSAMS). The vaccine was tested with two protocols, a single dose and a booster dose 6 months after the first dose. The FhSAMS vaccine proved to be safe, with no side effects. Furthermore, it was able to generate a more robust humoral immune response when a six‐month booster dose was used, in addition to stimulating greater production of IFN‐ʏ, indicating a Th1 profile immune stimulus. [ABSTRACT FROM AUTHOR]

Immune complexes (ICs) between antigens and antibodies are naturally immunogenic by virtue of enhanced uptake by antigen-presenting cells. Recombinant ICs have been generated by molecular engineering, which opens the path for scale-up manufacturing and consistent formulation. Several iterations of recombinant ICs have been generated and tested as vaccine candidates for immunogenicity and protection against infectious diseases. Plant biotechnology has emerged as an alternative and cheaper production system to mammalian cell platforms, raising the prospect for scalable, low-cost production of recombinant IC-based vaccines. Recombinant IC technology is now poised to enter the clinical phase of testing and development. New vaccine technologies are needed to combat many existing infections and prepare better for those that may emerge in the future. The conventional technologies that rely on protein-based vaccines are still severely restricted by the sparsity and poor accessibility of available adjuvants. One possible solution to this problem is to enhance antigen immunogenicity by a more natural means by complexing it with antibodies in the form of immune complexes (ICs). However, natural ICs are impractical as vaccines, and significant research efforts have been made to generate them in recombinant form, with plant bioengineering being at the forefront of these efforts. Here, we describe the challenges and progress made to date to make recombinant IC vaccines applicable to humans. [ABSTRACT FROM AUTHOR]

Chikungunya virus is an emerging mosquito-borne alphavirus that causes febrile illness and arthritic disease. Chikungunya virus is endemic in 110 countries and the World Health Organization estimates that it has caused more than 2 million cases of crippling acute and chronic arthritis globally since it re-emerged in 2005. Chikungunya virus outbreaks have occurred in Africa, Asia, Indian Ocean islands, South Pacific islands, Europe, and the Americas. Until recently, no specific countermeasures to prevent or treat chikungunya disease were available. To address this need, multiple vaccines are in human trials. These vaccines use messenger RNA-lipid nanoparticles, inactivated virus, and viral vector approaches, with a live-attenuated vaccine VLA1553 and a virus-like particle PXVX0317 in phase III testing. In November 2023, the US Food and Drug Administration (FDA) approved the VLA1553 live-attenuated vaccine, which is marketed as IXCHIQ. In June 2024, Health Canada approved IXCHIQ, and in July 2024, IXCHIQ was approved by the European Commission. On August 13, 2024, the US FDA granted priority review for PXVX0317. The European Medicine Agency is considering accelerated assessment review of PXVX0317, with potential for approval by both agencies in 2025. In this review, we summarize published data from pre-clinical and clinical trials for the IXCHIQ and PXVX0317 vaccines. We also discuss unanswered questions including potential impacts of pre-existing chikungunya virus immunity on vaccine safety and immunogenicity, whether long-term immunity can be achieved, safety in children, pregnant, and immunocompromised individuals, and vaccine efficacy in people with previous exposure to other emerging alphaviruses in addition to chikungunya virus. [ABSTRACT FROM AUTHOR]

Currently available seasonal influenza vaccines confer variable protection due to antigenic changes resulting from the accumulation of diverse mutations. The analysis of new seasonal influenza vaccines is challenging in part due to the limitations of the traditional hemagglutination inhibition (HAI) assay with A/H3N2 strains. An improved and objective novel HAI assay was developed with recombinant virus-like particles (VLPs) and an egg-derived virus as agglutinins, the oseltamivir treatment of VLPs, human red blood cells, and using an automated image reader-based analysis of hemagglutination. HAI validation was demonstrated using four VLPs and egg-derived strains, with 46–56 serum samples tested 12 times in duplicate per strain. The validated HAI assay was precise as indicated by the percent geometric coefficient of variation for intra-, inter-, and total assay precision, as well as accurate as evidenced by percent bias measurements. The assay exhibited linearity, specificity for homologous type/subtype strains, and sensitivity with a starting dilution of 1:10. Assay robustness and sample stability were demonstrated as a percentage difference compared to reference condition. Validated HAI results were equivalent for the single and duplicate sample testing and correlated well with a qualified live wild-type influenza microneutralization assay. These findings demonstrate the suitability of this high-throughput novel modified validated HAI assay for evaluating vaccine immunogenicity and efficacy. [ABSTRACT FROM AUTHOR]

Introduction: HIV-1 envelope (Env) is the key target for antibodies (Abs) against the virus and thus an important HIV-1 vaccine component. Env is synthesized from a gp160 precursor with a signal peptide (SP) at its N-terminus. This study investigated the influence of the SP on Env antigenicity and immunogenicity. Methods: Env proteins from two HIV-1 isolates, AA05 and AC02, were analyzed as gp120 and gp160 in their native wild-type (WT) forms and as chimeras with swapped SPs (AA05-02 and AC02-05). The WT and chimeric Env were assessed for antigenicity and glycosylation using monoclonal antibodies (mAbs) and glycan probes. Immunogenicity was tested in mice using three vaccine types: gp120 protein, gp120 DNA+gp120 protein, and gp120 DNA+gp160 DNA. Results: The recombinant AC02 gp120 protein was antigenically superior to AA05 as indicated by higher reactivity with most mAbs tested. When SPs were swapped, the antigenicity of the chimeric gp120s (AA05-02 and AC02-05) resembled that of the gp120s from which the SPs were derived; AA05-02 was similar to AC02 and vice versa. Glycan probe reactivity followed a similar pattern: AA05-02 and AC02 showed similar affinity to high-mannose specific mAbs and lectins. Interestingly, the antigenicity of gp160s showed an opposite pattern; membrane-bound gp160 expressed with the AA05 SP (AA05 and AC02-05) showed greater mAb binding than gp160 with the AC02 SP (AC02 and AA05-02). Mice immunized with gp120 protein showed that AA05-02 induced stronger cross-reactive binding Ab responses than AA05 WT, and AC02 elicited stronger responses than AC02-05, indicating AC02 SP enhanced gp120 immunogenicity. However, when DNA vaccines were included (gp120 DNA+gp120 protein and gp120 DNA+gp160 DNA), the use of heterologous SPs diminished the immunogenicity of the WT immunogens. Among the three vaccine regimens tested, only gp120 DNA+gp160 DNA immunization elicited low-level Tier 2 neutralizing Abs, with AA05 WT inducing Abs with greater neutralization capabilities than AA05-02. Conclusion: These data demonstrate that the SP can significantly impact the antigenicity and immunogenicity of HIV-1 Env proteins. Hence, while SP swapping is a common practice in constructing Env immunogens, this study highlights the importance of careful consideration of the effects of replacing native SPs on the immunogenicity of Env vaccines. [ABSTRACT FROM AUTHOR]

Background/Objectives: The receptor binding motif (RBM) of the SARS-CoV-2 spike protein is critical for viral entry into host cells. Development of a vaccine targeting this region is a promising strategy for COVID-19 prevention. To enhance the immunogenicity of SARS-CoV-2 vaccines, we developed an adenoviral vector expressing the RBM from the SARS-CoV-2 spike protein that fused to the human Fc (hFc) domain. Methods: The recombinant RBM_hFc fusion protein was successfully cloned into the pacAd5CMV-N-pA (pAd5) vector and expressed in HEK293 cells as a ~40 kDa protein. A recombinant adenovirus encoding RBM_hFc was subsequently generated and confirmed by cytopathic effect assay. Results: Western blot analysis verified the expression of RBM_hFc in the adenovirus (AdV). ELISA assays, validated for IgG detection, demonstrated a twofold increase in IgG antibody levels (M–1.090 at 450 nm; SD—±0.326; and 95% CI—0.250 [0.839 to 1.340]) in sera from BALB/c mice immunized with Ad/RBM_hFc, compared to the negative control group. Result suggests a robust humoral immune response induced by the Ad/RBM_hFc vaccine. Moreover, ELISpot assays demonstrated a tenfold increase in IFN-γ -producing cells (M—440 spot-forming cells; SD—±124.976; and 95% CI—75.522 [364.478 to 515.522]) in mice immunized with AdV/RBM_hFc compared to the negative control group. Result proved that AdV/RBM_hFc-stimulated a robust cellular immune response in animal model. Conclusions: Our findings indicate that the RBM_hFc fusion protein enhances both humoral and cellular immune responses. These results suggest the potential of adenoviral vectors carrying RBM_hFc as vaccine candidates. However, comprehensive evaluation of the protective efficacy of these adenoviral vectors will necessitate rigorous experimental studies. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. Methods: We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2–4 weeks following a fourth dose of XBB.1.5 mRNA vaccines. Results: Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each p < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each p < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each p < 0.01) but failed to induce infection-blocking IgA (each p > 0.05). Conclusion: XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks. [ABSTRACT FROM AUTHOR]

Background. The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines. There are currently no mRNA-based combined vaccines approved for use in humans. Some studies have shown that different mRNA components in a vaccine can interact to increase or decrease the immunogenicity and efficacy of the combined vaccine. Objectives. In the present study, we investigated the possibility of combining the mRNA vaccines, encoding seasonal influenza and SARS-CoV-2 antigens. In our previous works, both vaccine candidates have shown excellent immunogenicity and efficacy profiles in mice. Methods. The mRNA-LNPs were prepared by microfluidic mixing, immunogenicity in mice was assessed by hemagglutination inhibition assay, enzyme-linked immunoassay and virus neutralization assay. Immunological efficacy was assessed in a mouse viral challenge model. Results. In this work, we demonstrated that the individual mRNA components of the combined vaccine did not affect the immunogenicity level of each other. The combined vaccine demonstrated excellent protective efficacy, providing a 100% survival rate when mice were infected with the H1N1 influenza virus and reducing the viral load in the lungs. Four days after the challenge with SARS-CoV-2 EG.5.1.1., no viable virus and low levels of detectable viral RNA were observed in the lungs of vaccinated mice. Conclusions. The combination does not lead to mutual interference between the individual vaccines. We believe that such a combined mRNA-based vaccine could be a good alternative to separated human vaccinations for the prevention of COVID-19 and influenza. [ABSTRACT FROM AUTHOR]

Background: Vaccination is one of the effective measures to prevent latent tuberculosis infection (LTBI) from developing into active tuberculosis (TB). Applying bioinformatics methods to pre‐evaluate the biological characteristics and immunogenicity of vaccines can improve the efficiency of vaccine development. Objectives: To evaluate the immunogenicity of TB vaccine W541 and to explore the application of bioinformatics technology in TB vaccine research. Methods: This study concatenated the immunodominant sequences of Ag85A, Ag85B, Rv3407, and Rv1733c to construct the W541 DNA vaccine. Then, bioinformatics methods were used to analyze the physicochemical properties, antigenicity, allergenicity, toxicity, and population coverage of the vaccine, to identify its epitopes, and to perform molecular docking with MHC alleles and Toll‐like receptor 4 (TLR4) of the host. Finally, the immunogenicity of the vaccine was evaluated in animal experiments. Results: The W541 vaccine protein is a soluble cytoplasmic protein with a half‐life of 1.1 h in vivo and an instability index of 45.37. It has good antigenicity and wide population coverage without allergenicity and toxicity. It contains 138 HTL epitopes, 73 CTL epitopes, 8 linear and 14 discontinuous B cell epitopes, and has a strong affinity for TLR4. Immune simulations have shown that it can effectively stimulate innate and adaptive immune responses. Animal experiments confirmed that the W541 DNA vaccine could effectively activate Th1‐ and Th17‐type immune responses, producing high levels of IFN‐γ and IL‐17A, but could not significantly increase antibody levels. Conclusion: The W541 DNA vaccine can induce strong cellular immune responses. However, further optimization of the vaccine design is needed to make the expressed protein more stable in vivo. Bioinformatics analysis could reveal the physicochemical and immunological information of vaccines, which is critical for guiding vaccine design and development. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory Syncytial Virus (RSV) is a significant cause of respiratory illnesses worldwide, particularly in infants and elderly individuals. Despite the burden RSV imposes, effective preventive measures are limited. The research application of adeno-associated virus (AAV) in vaccine platforms has been expanding, and its potential in prevention and treatment has garnered much attention. Methods: In this study, we explored the potential application of a recombinant adeno-associated virus 5 (rAAV5) vector-based RSV vaccine, focusing on the expression of the pre-fusion (Pre-F) protein structure. Through intramuscular immunization in mice. The immunogenicity of the vaccine was evaluated in Balb/ c mice immunized intramuscularly and intranasal, respectively. Results: The rAAV5-RSV-Fm vaccine demonstrated positive humoral and induced antibody titers against RSV strains A and B for up to 120 days postimmunization. Notably, intranasal administration also elicited protective antibodies. Characterization studies confirmed the ability of the vac-cine to express the Pre-F protein and its superior immunogenicity compared to that of full-length F protein. Conclusion: These findings underscore the potential application of rAAV5 vector platforms in RSV vaccine development and further investigation into their protective efficacy is warranted. [ABSTRACT FROM AUTHOR]

Despite the cumulative evidence supporting HER3 as a target for antitumor therapies, no agents targeting HER3 have been approved for cancer treatment. Most of the agents evaluated in preclinical and clinical trials have been specific monoclonal antibodies (MAbs), with few examples of active immunotherapy directed against this receptor. However, some cancer vaccine formats may generate polyclonal antibodies (PAbs) that replicate the diverse effector mechanisms of MAbs, including ligand neutralization and receptor degradation. In this study, we developed a protein subunit-based monovalent vaccine candidate targeting the extracellular domain (ECD) of HER3. Immunization of mice with a formulation targeting murine ErbB3-ECD successfully overcome tolerance to this self-antigen, inducing high titers of ErbB3-specific PAbs. The antitumor potential of this formulation and the induced PAbs was demonstrated in vivo and in vitro in an ErbB3-overexpressing 3LL-D122-derived tumor model. The immunogenicity of the HER3-ECD-based vaccine candidate was confirmed by the induction of high titers of HER3-specific PAbs. Consistent with the initial results, HER3-ECD-targeting PAbs were cytotoxic in several human epithelial tumor cell lines and exerted antitumor effects in vivo. These results support the value of HER3 as a tumor antigen and the effector mechanisms of HER3-specific therapeutic MAbs, while suggesting the potential of the proposed vaccine candidate for the treatment of HER3-expressing carcinomas. [ABSTRACT FROM AUTHOR]

Background The adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50–59 years without or with increased risk for RSV disease due to specific chronic medical conditions. Methods This observer-blind, phase 3, noninferiority trial included adults aged 50–59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50–59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. Results The exposed population included 1152 participants aged 50–59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50–59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. Conclusions RSVPreF3 OA was immunologically noninferior in 50–59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50–59-year-olds was consistent with that in ≥60-year-olds. Clinical Trial Registration ClinicalTrials.gov : NCT05590403. [ABSTRACT FROM AUTHOR]

Background We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds. Methods This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed. Results Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06–1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups. Conclusions Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine. Clinical Trials Registration NCT05568797 [ABSTRACT FROM AUTHOR]

The immunocompromised population was disproportionately affected by the severe acute respiratory syndrome coronavirus 2 pandemic. However, these individuals were largely excluded from clinical trials of vaccines, monoclonal antibodies, and small molecule antivirals. Although the community of scientists, clinical researchers, and funding agencies have proven that these therapeutics can be made and tested in record time, extending this progress to vulnerable and medically complex individuals from the start has been a missed opportunity. Here, we advocate that it is paramount to plan for future pandemics by investing in specific clinical trial infrastructure for the immunocompromised population to be prepared when the need arises. [ABSTRACT FROM AUTHOR]

Background Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings. Methods This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in 5 sub-Saharan African countries included people without human immunodeficiency virus (HIV) (PWOH, n = 249) and people with HIV (PWH, n = 250). Adult participants received 1 of 2 accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.ZEBOV administered 14 days apart [n = 79] or Ad26.ZEBOV, MVA-BN-Filo administered 28 days apart [n = 322]) or saline/placebo (n = 98). The primary endpoints were safety (adverse events [AEs]) and immunogenicity (Ebola virus [EBOV] glycoprotein–specific binding antibody responses). Binding antibody responders were defined as participants with a >2.5-fold increase from baseline or the lower limit of quantification if negative at baseline. Results The mean age was 33.4 years, 52% of participants were female, and among PWH, the median CD4+ cell count was 560.0 (interquartile range, 418.0–752.0) cells/μL. AEs were generally mild/moderate with no vaccine-related serious AEs or remarkable safety profile differences by HIV status. At 21 days post–dose 2, EBOV glycoprotein–specific binding antibody response rates in vaccine recipients were 99% for the 14-day regimen (geometric mean concentrations [GMCs]: 5168 enzyme-linked immunosorbent assay units [EU]/mL in PWOH; 2509 EU/mL in PWH) and 98% for the 28-day regimen (GMCs: 6037 EU/mL in PWOH; 2939 EU/mL in PWH). At 12 months post–dose 2, GMCs in PWOH and PWH were 635 and 514 EU/mL, respectively, for the 14-day regimen and 331 and 360 EU/mL, respectively, for the 28-day regimen. Conclusions Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PWH in Africa. Clinical Trials Registration.  NCT02598388. [ABSTRACT FROM AUTHOR]

Background We report data from stage 1 of an ongoing 2-staged, phase 1/2 randomized clinical trial with a 4-component generalized modules for membrane antigens-based vaccine against Shigella sonnei and Shigella flexneri 1b, 2a, and 3a (altSonflex1-2-3; GSK). Methods Europeans aged 18–50 years (N = 102) were randomized (2:1) to receive 2 injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at prespecified time points. Results The most common solicited administration-site event (until 7 days after each injection) and unsolicited adverse event (until 28 days after each injection) were pain (altSonflex1-2-3, 97.1%; placebo, 58.8%) and headache (32.4%; 23.5%), respectively. All serotype-specific functional IgG antibodies peaked 14–28 days after injection 1 and remained substantially higher than prevaccination at 3 or 6 months postvaccination; the second injection did not boost but restored the initial immune response. The highest seroresponse rates (≥4-fold increase in titers over baseline) were obtained against S. flexneri 2a (enzyme-linked immunosorbent assay [ELISA] after injection 1, 91.0%; after injection 2 [day 113; day 197], 100%; 97.0% and serum bactericidal activity [SBA] after injection 1, 94.4%; after injection 2, 85.7%; 88.9%) followed by S. sonnei (ELISA after injection 1, 77.6%; after injection 2, 84.6%; 78.8% and SBA after injection 1, 83.3%; after injection 2, 71.4%; 88.9%). Immune responses against S. flexneri 1b and S. flexneri 3a, as measured by both ELISA and SBA, were numerically lower compared to those against S. sonnei and S. flexneri 2a. Conclusions No safety signals or concerns were identified. altSonflex1-2-3 induced functional serotype-specific immune responses, allowing further clinical development in the target population. Clinical Trials Registration. NCT05073003. [ABSTRACT FROM AUTHOR]

Flaviviruses represent a significant global health threat and relatively few licensed vaccines exist to protect against them. Insect-specific flaviviruses (ISFVs) are incapable of replication in humans and have emerged as a novel and promising tool for flavivirus vaccine development. ISFV-based flavivirus vaccines have shown exceptional safety, immunogenicity, and efficacy, however, a detailed assessment of the correlates of protection and immune responses induced by these vaccines are still needed for vaccine optimization. Here, we explore the mechanisms of protective immunity induced by a previously created pre-clinical Zika virus (ZIKV) vaccine candidate, called Aripo/Zika (ARPV/ZIKV). In brief, immunocompromised IFN-αβR-/- mice passively immunized with ARPV/ZIKV immune sera experienced protection after lethal ZIKV challenge, although this protection was incomplete. ARPV/ZIKV-vaccinated IFN-αβR-/- mice depleted of CD4+ or CD8+ T-cells at the time of ZIKV challenge showed no morbidity or mortality. However, the adoptive transfer of ARPV/ZIKV-primed T-cells into recipient IFN-αβR-/- mice resulted in a two-day median increase in survival time compared to controls. Altogether, these results suggest that ARPV/ZIKV-induced protection is primarily mediated by neutralizing antibodies at the time of challenge and that T-cells may play a comparatively minor but cumulative role in the protection observed. Lastly, ARPV/ZIKV-vaccinated Tcra KO mice, which are deficient in T-cell responses, experienced significant mortality post-challenge. These results suggest that ARPV/ZIKV-induced cell-mediated responses are critical for development of protective immune responses at vaccination. Despite the strong focus on neutralizing antibody responses to novel flavivirus vaccine candidates, these results suggest that cell-mediated responses induced by ISFV-based vaccines remain important to overall protective responses. Author summary: Conventional vaccine development platforms may involve trade-offs between vaccine safety and immunogenicity, but insect-specific viruses have recently emerged as a promising platform to overcome this challenge. We previously developed a preclinical Zika virus (ZIKV) vaccine candidate named Aripo/Zika virus (ARPV/ZIKV) based on a novel ISFV called Aripo virus (ARPV). Our previous studies demonstrated the high degree of safety as well as the single dose efficacy of ARPV/ZIKV. Here, we begin to elucidate the mechanisms of protection for this vaccine candidate. We demonstrate the dominant role of neutralizing antibodies in providing protection post-challenge, but also the importance of ARPV/ZIKV-induced T-cell responses in the priming phase of immunity. Overall, even high efficacy ISFV-based vaccine candidates such as ARPV/ZIKV may benefit from adjuvants or optimization strategies to increase protective T-cell responses. However, ARPV/ZIKV remains a promising ZIKV vaccine candidate, and contributes to the rapidly growing body of work that supports the potential of ISFVs as a new tool for protecting the health of the millions of people currently at risk of infection. [ABSTRACT FROM AUTHOR]

Motivation Tumor polyvalent neoantigen mRNA vaccines are gaining prominence in immunotherapy. The design of sequences in vaccine development is crucial for enhancing both the immunogenicity and safety of vaccines. However, a major challenge lies in selecting the optimal sequences from the large pools generated by multiple peptide combinations and synonymous codons. Results We introduce NeoDesign, a computational tool designed to tackle the challenge of sequence design. NeoDesign comprises four modules: Library Construction, Optimal Path Filtering, Linker Addition, and λ-Evaluation. It aims to identify the optimal protein sequence for tumor polyvalent neoantigen vaccines by minimizing linker usage, avoiding unexpected neoantigens and functional domains, and simplifying the structure. It also provides a preference scheme to balance mRNA stability and protein expression when designing mRNA sequences for the optimal protein sequence. This tool can potentially improve the sequence design of tumor polyvalent neoantigen mRNA vaccines, thereby significantly advancing immunotherapy strategies. Availability and implementation NeoDesign is freely available on https://github.com/HuangLab-Fudan/neoDesign and https://figshare.com/projects/NeoDesign/221704. [ABSTRACT FROM AUTHOR]

COVID-19 vaccine evaluations are mainly focused on antibody analyses, but there is growing interest in measuring the cellular immune responses from the researchers evaluating these vaccines. The cellular responses to several COVID-19 vaccines have been studied using the enzyme-linked immunospot (ELISPOT) assay for IFN-γ. However, the ELISPOT assay is no longer used only for research purpose and so the performance of this assay must be validated. Since the bioanalytical validation of ELISPOT-IFN-γ is essential for evaluating the method's effectiveness and establishing confidence in a vaccine's immunogenicity, the present work validates the ELISPOT-IFN-γ assay's performance in determining the frequency of IFN-γ-producing cells after stimulation with the SARS-CoV-2 spike protein. The validation was performed in peripheral blood mononuclear cells from volunteers immunized with anti-COVID-19 vaccines. According to the findings, the LOD was 17 SFU and the LLOQ was 22 SFU, which makes the method highly sensitive and suitable for evaluating low levels of cellular responses. The procedure's accuracy is confirmed by the correlation coefficients for the spike protein and anti-CD3+, being 0.98 and 0.95, respectively. The repeatability and intermediate precision tests were confirmed to be reliable by obtaining a coefficient of variation of ≤25%. The results obtained in this validation enable the assay to be employed for studying antigen-specific cells and evaluating cellular responses to vaccines. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant brain tumors, such as glioblastoma (GBM), are devastating diagnoses for patients and their families, as these tumors are difficult to fully remove with surgery and respond poorly to chemotherapy and radiation. Immunotherapy is a novel approach to treating cancer, as these therapies are intended to initiate robust antitumor immune responses. However, immunotherapy for GBM has largely been unsuccessful. It is hypothesized that one of the major contributors to immunotherapy failure in GBM patients is the number of immunosuppressive blockades present in these patients. Often, the GBM microenvironment is characterized as highly immunosuppressive due to GBM recruiting anti-inflammatory immune cells to the microenvironment and releasing immunosuppressive factors such as PD-L1. Additionally, treatment given to GBM patients, such as corticosteroids, is immunosuppressive. In this review, we outline potential blockades to immunotherapy success in GBM patients to highlight where new approaches to combatting this malignancy should be considered. Glioblastoma (GBM) is an aggressive primary brain tumor depicted by a cold tumor microenvironment, low immunogenicity, and limited effective therapeutic interventions. Its location in the brain, a highly immune-selective organ, acts as a barrier, limiting immune access and promoting GBM dissemination, despite therapeutic interventions. Currently, chemotherapy and radiation combined with surgical resection are the standard of care for GBM treatment. Although immune checkpoint blockade has revolutionized the treatment of solid tumors, its observed success in extracranial tumors has not translated into a significant survival benefit for GBM patients. To develop effective immunotherapies for GBM, it is vital to tailor treatments to overcome the numerous immunosuppressive barriers that inhibit T cell responses to these tumors. In this review, we address the unique physical and immunological barriers that make GBM challenging to treat. Additionally, we explore potential therapeutic mechanisms, studied in central nervous system (CNS) and non-CNS cancers, that may overcome these barriers. Furthermore, we examine current and promising immunotherapy clinical trials and immunotherapeutic interventions for GBM. By highlighting the array of challenges T cell-based therapies face in GBM, we hope this review can guide investigators as they develop future immunotherapies for this highly aggressive malignancy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: American Indian and Alaska Native (AI/AN) infants historically experienced a disproportionate burden of invasive Haemophilus influenzae type b (Hib) disease, especially early in life. PedvaxHIB vaccine is preferentially recommended for AI/AN infants because it elicits protective antibody levels postdose 1. Vaxelis, a hexavalent vaccine that contains the same Hib conjugate as PedvaxHIB but at lower concentration, is recommended for US children, but postdose 1 Hib immunogenicity data are needed to inform whether a preferential recommendation should be made for AI/AN infants. METHODS: We conducted a phase IV randomized, open-label, noninferiority trial comparing postdose 1 immunogenicity of Vaxelis to PedvaxHIB in AI/AN infants. Participants were randomized to receive a primary series of PedvaxHIB or Vaxelis. Serum samples collected 30 days postdose 1 were tested for anti-Hib immunoglobulin G antibody by enzyme-linked immunosorbent assay. The anti-Hib immunoglobulin G geometric mean concentration (GMC) ratio (Vaxelis/PedvaxHIB) was estimated by constrained longitudinal data analysis. Noninferiority was defined a priori as the lower bound of the 95% confidence interval (CI) of the GMC ratio ≥0.67. RESULTS: A total of 327 of the 333 infants enrolled in the study were included in the per-protocol analysis. The postdose 1 anti-Hib GMC was 0.41 µg/mL (95% CI 0.33-0.52) in the Vaxelis group (n = 152) and 0.39 µg/mL (95% CI 0.31-0.50) in the PedvaxHIB group (n = 146). The constrained longitudinal data analysis GMC ratio was 1.03 (95% CI 0.76-1.39). CONCLUSIONS: Postdose 1 immunogenicity of Vaxelis was noninferior to PedvaxHIB. Our findings support the use of Vaxelis in AI/AN children, a population with elevated risk of Hib disease. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic posed significant challenges worldwide, with SARS-CoV-2 vaccines critical in reducing morbidity and mortality. This study evaluates the immunogenicity and antibody persistence of the BNT162b2 vaccine in people living with HIV (PLWH). Methods: We monitored anti-SARS-CoV-2 Spike IgG concentration in a cohort of PLWH at five time points (T0–T4) using chemiluminescent microparticle immunoassays (CMIAs) at the baselined both during and after vaccination. In severely immunocompromised individuals, a boosting dose was recommended, and participants and IgG concentration were measured in the two subgroups (boosted and not boosted). Results: In total, 165 PLWH were included, and 83% were male with a median age of 55 years (IQR: 47–62). At T1, 161 participants (97.6%) showed seroconversion with a median of IgG values of 468.8 AU/mL (IQR: 200.4–774.3 AU/mL). By T2, all subjects maintained a positive result, with the median anti-SARS-CoV-2 Spike IgG concentration increasing to 6191.6 AU/mL (IQR: 3666.7–10,800.8 AU/mL). At T3, all participants kept their antibody levels above the positivity threshold with a median of 1694.3 AU/mL (IQR: 926.3–2966.4 AU/mL). At T4, those without a booster dose exhibited a marked decrease to a median of 649.1 AU/mL (IQR: 425.5–1299.8 AU/mL), whereas those with a booster experienced a significant increase to a median of 13,105.2 AU/mL (IQR: 9187.5–18,552.1 AU/mL). The immune response was negatively influenced by the presence of dyslipidaemia at T1 (aOR 4.75, 95% CI: 1.39–16.20) and diabetes at T3 (aOR 7.11, 95% CI: 1.10–46.1), while the use of protease inhibitors (aORs 0.06, 95% CI: 0.01–0.91) and being female (aOR 0.02, 95% CI: 0.01–0.32) at T3 were protective factors. Conclusions: The immunogenicity of the BNT162b2 vaccine in PLWH has been confirmed, with booster doses necessary to maintain high levels of anti-SARS-CoV-2 Spike IgG antibodies, especially in patients with comorbidities. These findings underline the importance of a personalized vaccination strategy in this population. [ABSTRACT FROM AUTHOR]

Background: The SARS-CoV-2 virus continuously acquires mutations, leading to the emergence of new variants. Notably, the effectiveness of global vaccination efforts has significantly declined with the rise and spread of the B.1.1.529 (Omicron) variant. Methods: The study used virological, immunological and histological research methods, as well as methods of working with laboratory animals. In this study, we evaluated the Gam-COVID-Vac (Sputnik V), an adenoviral vaccine developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology, and conducted experiments on hemizygous K18-ACE2-transgenic F1 mice. The variants studied included B.1.1.1, B.1.1.7, B.1.351, B.1.1.28/P.1, B.1.617.2, and B.1.1.529 BA.5. Results: Our findings demonstrate that the Sputnik V vaccine elicits a robust humoral and cellular immune response, effectively protecting vaccinated animals from challenges posed by various SARS-CoV-2 variants. However, we observed a notable reduction in vaccine efficacy against the B.1.1.529 (Omicron BA.5) variant. Conclusions: Our results indicate that ongoing monitoring of emerging mutations is crucial to assess vaccine efficacy against new SARS-CoV-2 variants to identify those with pandemic potential. If protective efficacy declines, it will be imperative to develop new vaccines tailored to current variants of the virus. [ABSTRACT FROM AUTHOR]

The use of Vaccinia virus (VACV) as a preventive vaccine against variola, the etiological agent of smallpox, led to the eradication of smallpox as a human disease. The L1 protein, a myristylated transmembrane protein present on the surface of mature virions, plays a significant role in infection and morphogenesis, is well-conserved in all orthopoxviruses, and is the target of neutralizing antibodies. DNA recombinant vaccines expressing this protein were successfully used, but they showed lower efficacy in non-human and human primates when used alone, and viral-vectored fowlpox vaccines were already proved to increase immunogenicity when used as a boost. Here, we constructed a novel fowlpox-based recombinant (FPtPA-L1R), in which the tissue plasminogen activator signal sequence was linked to the 5′ end of the L1R gene to drive the L1 protein into the cellular secretion pathway. FPtPA-L1R expresses a functional heterologous protein that can be immunoprecipitated by hyperimmune rabbit serum. The protein shows cytoplasmic and membrane subcellular localizations and long-lasting expression in CEF, non-human primate Vero and human MRC-5 cells. The tissue plasminogen activator signal sequence can thus contribute significantly to the expression of the L1 protein and may enhance the immunogenicity of a putative DNA/FP prime–boost vaccine. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 evolution trajectory remains uncertain, and the antigenic characteristics of future variants are highly unpredictable. We report the immunogenicity and safety of multivalent COVID-19 vaccines, SCTV01E and SCTV01E-1, against Omicron BA.5. This phase 2 trial randomized 400 adults into two cohorts, 160 unvaccinated (3 doses) and 240 previously vaccinated (2 doses) individuals to receive 30 µg SCTV01E-1 or 30 µg SCTV01E (1:1) between 4 November and 28 November 2022. Among the unvaccinated cohort, day 42 geometric mean fold rises (GMFRs) of neutralizing antibodies (nAb) against Omicron BA.5 were reported to be 12.8× and 20.5× over day 0 for SCTV01E-1 and SCTV01E, respectively. On day 178, both vaccines increased geometric mean titers (GMTs) of nAb against BA.5 following the booster dose compared to pre-booster levels on D150. Similar frequencies of solicited [6.2% (5/81) and 7.6% (6/79)] and unsolicited [11.1% (9/81) and 10.1% (8/79)] adverse events (AEs) were reported in SCTV01E-1 and SCTV01E groups, respectively. Grade 3 or more AEs were < 2% in both vaccine groups [SCTV01E-1: 1.2% (1/81), SCTV01E: 1.3% (1/79)]. In the previously vaccinated cohort, similar GMFRs were reported on day 28 (SCTV01E-1: 9.4× and SCTV01E: 8.7×) over baseline (D0). On day 148, both vaccines showed increased nAb levels with similar GMFRs over D120. Comparable incidences of solicited [13.2% (16/121) and 10.9% (13/119)] and unsolicited [17.4% (21/121) and 10.9% (13/119)] AEs were reported in SCTV01E-1 and SCTV01E groups, respectively. Numerically identical ≥ grade 3 AEs [SCTV01E-1: 1.7% (2/121) and SCTV01E: 1.7% (2/119)] were reported. This trial demonstrates the effectiveness of updated multivalent vaccines with acceptable safety profiles. [ABSTRACT FROM AUTHOR]

Background: Shigellosis is the leading cause of diarrheal deaths worldwide and is particularly dangerous in children under 5 years of age in low- and middle-income countries. Additionally, the rise in antibiotic resistance has highlighted the need for an effective Shigella vaccine. Previously, we have used the Multiple Antigen-Presenting System (MAPS) technology to generate monovalent and quadrivalent Salmonella MAPS vaccines that induce functional antibodies against Salmonella components. Methods: In this work, we detail the development of several monovalent vaccines using O-specific polysaccharides (OSPs) from four dominant serotypes, S. flexneri 2a, 3a, and 6, and S. sonnei. We tested several rhizavidin (rhavi) fusion proteins and selected a Shigella-specific protein IpaB. Quadrivalent MAPS were made with Rhavi-IpaB protein and tested in rabbits for immunogenicity. Results: Individual MAPS vaccines generated robust, functional antibody responses against both IpaB and the individual OSP component. Antibodies to IpaB were effective across Shigella serotypes. We also demonstrate that the OSP antibodies generated are specific to each homologous Shigella O type by performing ELISA and bactericidal assays. We combined the components of each MAPS vaccine to formulate a quadrivalent MAPS vaccine which elicited similar antibody and bactericidal responses compared to their monovalent counterparts. Finally, we show that the quadrivalent MAPS immune sera are functional against several clinical isolates of the serotypes used in the vaccine. Conclusions: This quadrivalent MAPS Shigella vaccine is immunogenicity and warrants further study. [ABSTRACT FROM AUTHOR]

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[Display omitted] Cancer immunotherapy has emerged as a potent treatment strategy by harnessing the host immune system to target cancer cells. However, challenges including low tumor vaccine immunogenicity and tumor heterogeneity hinder its clinical efficacy. To address these issues, we propose a novel nanoplatform integrating photothermal material gold nanorods (GNRs) with polyphenols for enhanced immunotherapy efficacy via photothermal therapy. Polyphenols, natural compounds with phenolic hydroxyl groups, are known for their ability to bind tightly to various molecules, making them ideal for antigen capture. We synthesized GNRs modified with polyphenols (GNR-PA and GNR-GA) and demonstrated their ability to induce immunogenic cell death upon laser irradiation, releasing tumor-associated antigens (TAAs). The surface polyphenols on GNRs effectively captured released TAAs to shield them from clearance. In vivo studies confirmed increased accumulation of GNR-GA in lymph nodes and enhanced dendritic cell maturation, leading to promoted effector T cell infiltration into tumors. Furthermore, treatment combined with PD-1/PD-L1 pathway blockade demonstrated potent tumor regression and systemic immunotherapy efficacy. Our findings highlight the potential of this photothermal nanoplatform as a promising strategy to overcome the limitations of current cancer immunotherapy approaches and improve therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Abstract The hepatitis A virus (HAV) vaccine is highly immunogenic in general, yet data on its use in liver-transplanted (LT) children is limited. This study aimed to determine the seroimmunity to HAV in all LT children, and the immunogenicity of an inactivated HAV vaccine in seronegative LT children at King Chulalongkorn Memorial Hospital. Seronegative LT children received the inactivated HAV vaccine at 0 and 6–8 months with adverse events monitored for 3 days post-immunization. The result reviewed that among 105 LT children, vaccination records were available for 81%, of which 7.1% and 16.5% with one and two doses of HAV vaccine were immunized before transplantation, respectively. Post-transplantation, 20.1% were seropositive for HAV, with 9.5% due to pre-transplant immunization. Eighty-three seronegative LT children (aged 7.25 ± 4.40 years; 48.6% male) received two vaccine doses. The seropositive rate increased following the first and second doses and reached to 51.5%, and 92.9%, respectively (p

The hepatitis A virus (HAV) vaccine is highly immunogenic in general, yet data on its use in liver-transplanted (LT) children is limited. This study aimed to determine the seroimmunity to HAV in all LT children, and the immunogenicity of an inactivated HAV vaccine in seronegative LT children at King Chulalongkorn Memorial Hospital. Seronegative LT children received the inactivated HAV vaccine at 0 and 6–8 months with adverse events monitored for 3 days post-immunization. The result reviewed that among 105 LT children, vaccination records were available for 81%, of which 7.1% and 16.5% with one and two doses of HAV vaccine were immunized before transplantation, respectively. Post-transplantation, 20.1% were seropositive for HAV, with 9.5% due to pre-transplant immunization. Eighty-three seronegative LT children (aged 7.25 ± 4.40 years; 48.6% male) received two vaccine doses. The seropositive rate increased following the first and second doses and reached to 51.5%, and 92.9%, respectively (p < 0.001), with no serious adverse events reported. Age at vaccination and the interval from transplantation to vaccination were risk factors for non-responsiveness (p < 0.001). The study highlighted inadequate HAV vaccination coverage, leaving most LT children susceptible to infection. HAV vaccine proved highly immunogenic and safe, emphasizing the need for improved vaccination strategies before and after liver transplantation. Trial registration TCTR20220110001. [ABSTRACT FROM AUTHOR]

Background: Current treatments and prevention strategies for echinococcosis are inadequate. Recent advancements in molecular vaccine development show promise against Echinococcus granulosus; however, Echinococcus multilocularis remains a challenge. A Multi-epitope Vaccine could potentially induce specific B and T lymphocyte responses, thereby offering protection against Echinococcus multilocularis infection. Methods: This study aimed to develop a MEV against alveolar echinococcosis. Key epitopes from the Echinococcus multilocularis proteins EmTSP3 and EmTIP were identified using immunoinformatics analyses. These analyses were conducted to assess the MEV feasibility, structural characteristics, molecular docking, molecular dynamics simulations, and immune simulations. The immunogenicity and antigenicity of the vaccine were evaluated through in vitro and in vivo experiments, employing ELISA, Western blotting, FCM, challenge infection experiments, and ELISPOT. Results: The effective antigenicity and immunogenicity of MEV were demonstrated through immunoinformatics, as well as in vitro and in vivo experiments. In vitro experiments revealed that MEV increased the secretion of IFN-g and IL-4 in PBMC and successfully bound to specific antibodies in patient serum. Furthermore, mice immunized with MEV developed a robust immune response, characterized by elevated levels of CD4+ and CD8+ T-cells, increased secretion of IFN-g and IL-4 by specific Th1 and Th2 cells, and heightened serum antibody levels. Importantly, MEV reduced the weight of cysts by conferring resistance against echinococcosis. These findings suggest that MEV is a promising candidate for the prevention of Echinococcus multilocularis infection. Conclusion: A total of 7 CTL, 7 HTL, 5 linear B-cell, and 2 conformational B-cell epitopes were identified. The vaccine has demonstrated effective antigenicity and immunogenicity against AE through molecular docking, immune simulation, molecular dynamics studies, and both in vitro and in vivo experiments. It provides effective protection against Echinococcus multilocularis infection, thereby laying a foundation for further development. [ABSTRACT FROM AUTHOR]

Picornaviridae are non-enveloped ssRNA viruses that cause diseases such as poliomyelitis, hand-foot-and-mouth disease (HFMD), hepatitis A, encephalitis, myocarditis, and foot-and-mouth disease (FMD). Virus-like particles (VLPs) vaccines mainly comprise particles formed through the self-assembly of viral capsid proteins (for enveloped viruses, envelope proteins are also an option). They do not contain the viral genome. On the other hand, the nanoparticles vaccine (NPs) is mainly composed of self-assembling biological proteins or nanomaterials, with viral antigens displayed on the surface. The presentation of viral antigens on these particles in a repetitive array can elicit a strong immune response in animals. VLPs and NPs can be powerful platforms for multivalent antigen presentation. This review summarises the development of virus-like particle vaccines (VLPs) and nanoparticle vaccines (NPs) against picornaviruses. By detailing the progress made in the fight against various picornaviruses such as poliovirus (PV), foot-and-mouth disease virus (FMDV), enterovirus (EV), Senecavirus A (SVA), and encephalomyocarditis virus (EMCV), we in turn highlight the significant strides made in vaccine technology. These advancements include diverse construction methods, expression systems, elicited immune responses, and the use of various adjuvants. We see promising prospects for the continued development and optimisation of VLPs and NPs vaccines. Future research should focus on enhancing these vaccines' immunogenicity, stability, and delivery methods. Moreover, expanding our understanding of the interplay between these vaccines and the immune system will be crucial. We hope these insights will inspire and guide fellow researchers in the ongoing quest to combat picornavirus infections more effectively. [ABSTRACT FROM AUTHOR]

Shigellosis, caused by the Gram-negative bacterium Shigella, is a major global health challenge. Despite extensive research over the past two decades, no commercial vaccine is available to prevent Shigella infection. Developing multi-epitope vaccines offers a promising and innovative approach to tackling infectious diseases. In this study, we produced a multi-epitope vaccine candidate using E. coli BL21 (DE3) plysS bacteria and purified the vaccine protein with Ni-NTA affinity chromatography. We then prepared alginate nanoparticles containing the vaccine protein, with a particle size of 122 ± 6 nm, PDI 0.17, SPAN 0.83, and zeta potential of -27 ± 2 mV. Successful protein loading was confirmed through nanodrop and ATR-FTIR analyses. To evaluate the immunogenicity of the encapsulated vaccine, mice were orally vaccinated, and their serum was analyzed for IgG, IL-4, and IFN-γ levels cytokines. The results showed a significant increase in IgG level in the vaccinated group compared to controls. Additionally, the vaccinated group exhibited a notable increase in IL-4 and IFN-γ cytokines, indicating a robust Th-cell-mediated immune response essential for combating Shigella. Our nano-vaccine demonstrated high efficacy in activating both humoral and cellular immunity, effectively protecting against the bacteria. The alginate-based oral vaccine candidate thus emerges as a promising strategy for developing a multi-epitope vaccine candidate against Shigella. [ABSTRACT FROM AUTHOR]

Background Rotavirus is a leading cause of severe pediatric gastroenteritis; 2 highly effective vaccines are used in the United States (US). We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. Methods Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) is a birth cohort of 245 mother-child pairs enrolled in 2017–2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as reverse-transcription polymerase chain reaction detection of rotavirus vaccine virus in stools collected 4–28 days after dose 1. Seroconversion was defined as a 3-fold rise in immunoglobulin A between the 6-week and 6-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. Results Prevaccination immunoglobulin G (IgG) (odds ratio [OR], 0.84 [95% confidence interval {CI},.75–.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("nonsecretors") with nonsecretor mothers, versus all other combinations (OR, 0.37 [95% CI,.16–.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose 1. Prevaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. Conclusions In this US cohort, prevaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response. [ABSTRACT FROM AUTHOR]

Background: Pregnancy is a critical time for women, making them more susceptible to infectious diseases like COVID-19. This study aims to determine the immunogenicity of COVID-19 in pregnant women who have been infected compared to those who have received the inactive COVID-19 vaccine. Materials and methods: In this retrospective cohort study, pregnant women who received the inactivated COVID-19 vaccine (Sinopharm) and those with a history of COVID-19 infection during pregnancy were studied. Participants who had experienced stillbirth, received different COVID-19 vaccines, or had intrauterine fetal death were excluded from the study. Overall, the study included 140 participants. The participants were divided into two groups of 70 participants - pregnant women who received the Sinopharm vaccine and pregnant women who had COVID-19 infection during pregnancy. Before delivery, blood samples were collected from all mothers to evaluate the maternal immunoglobulin G (IgG) level. Blood samples were also taken from the baby's umbilical cord during delivery to measure the newborn's IgG level. Additionally, blood samples were collected from babies whose mothers showed signs of acute infection to measure their IgM levels and evaluate vertical transmission. Findings: The study found a significant relationship between the mean level of maternal IgG and umbilical cord IgG within the groups (P < 0.001). The highest levels of maternal IgG (2.50 ± 2.17) and umbilical cord IgG (2.43 ± 2.09) were observed in pregnant women with a previous COVID-19 infection and no history of vaccination (P < 0.001). Only one baby was born with a positive IgM, and this baby was born to a mother who showed signs of COVID-19 infection in the last five days of pregnancy. The mother was 28 years old, with a BMI of 33; it was her first pregnancy, and she gave birth to a male newborn at term. Conclusion: Administering an inactivated vaccine during pregnancy can generate immunity in both the mother and the child. However, the vaccine's immunity level may not be as potent as that conferred by COVID-19 infection during pregnancy. Nonetheless, the risk of vertical transmission of COVID-19 is considered minimal and can be classified as negligible. [ABSTRACT FROM AUTHOR]

Melanoma is known to be the most hazardous and life‐threatening type of skin cancer. Although numerous treatments have been authorized in recent years, they often result in severe side effects and may not fully cure the disease. To combat this issue, immunotherapy has emerged as a promising approach for the prevention and treatment of melanoma. Specifically, the use of epitope melanoma vaccine, a subset of immunotherapy, has recently gained attention. The aim of this study was to create a multi‐epitope melanoma vaccine using immunoinformatic methods. Two well‐known antigens, NYESO‐1 and MAGE‐C2, were selected due to their strong immunogenicity and high expression in melanoma. To enhance the immunogenicity of the peptide vaccine, Brucella cell‐surface protein 31 (BCSP31), the G5 domain of resuscitation‐promoting factor B (RpfB) adjuvants, and the helper epitope of pan HLADR‐binding epitope (PADRE) were incorporated to vaccine construct. These different segments were connected with suitable linkers and the resulting vaccine structure was evaluated for its physicochemical, structural, and immunological properties using computational tools. The designed vaccine was found to have satisfactory allergenicity, antigenicity, and physicochemical parameters. Additionally, a high‐quality tertiary structure of the vaccine was achieved through modeling, refinement, and validation. Docking and molecular dynamics studies showed that the vaccine had a stable and appropriate interaction with the cognate TLR2 and TLR4 receptors during the simulation period. Finally, in silico immune simulation analysis revealed a significant increase in the levels of helper and cytotoxic T cells, as well as the cytokines interferon‐gamma and interleukin‐2, after repeated exposure to the melanoma vaccine. These results suggest that the designed vaccine has the potential to be an effective therapeutic option for melanoma. However, additional in vitro and in vivo validations are crucial to assess real‐world efficacy and safety. [ABSTRACT FROM AUTHOR]

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