Search

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]

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]

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]

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]

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]

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: 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]

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]

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]

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]

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia among adults in Western countries. Despite the introduction of targeted therapies, including first-line Bruton's tyrosine kinase inhibitor (BTKi) treatment, CLL remains largely incurable. Frequent disease relapses occur due to remaining treatment-resistant CLL cells, calling for novel therapies to eliminate minimal residual disease (MRD). Peptide-based vaccination targeting human leucocyte antigen (HLA)-presented CLL-associated antigens represents a promising, low-side-effect therapeutic option to optimize treatment responses and eliminate residual tumor cells by inducing an anti-leukemic immune response. The iVACXS15-CLL01 trial is an open-label, first-in-human (FIH) Phase I trial, evaluating the CLL-VAC-XS15 vaccine in CLL patients undergoing BTKi-based therapy. The vaccine was developed from HLA-presented CLL-associated antigen peptides, identified through comparative mass-spectrometry-based immunopeptidome analyses of CLL versus healthy samples in a previous study. To facilitate rapid and cost-effective deployment, vaccine peptides are selected for each patient from a pre-manufactured "peptide warehouse" based on the patient's individual HLA allotype and CLL immunopeptidome. The trial enrolls 20 CLL patients, who receive up to three doses of the vaccine, adjuvanted with the toll-like-receptor (TLR) 1/2 ligand XS15 and emulsified in Montanide ISA 51 VG. The primary objective of the iVAC-XS15-CLL01 trial is to assess the safety and immunogenicity of the CLL-VAC-XS15 vaccine. Secondary objectives are to Frontiers in evaluate the vaccine impact on MRD, progression-free survival, and overall survival, as well as comprehensive immunophenotyping to characterize vaccine-induced T-cell responses. This Phase I trial aims to advance CLL treatment by enhancing immune-mediated disease clearance and guiding the design of subsequent Phase II/III trials to implement a new therapeutic strategy for CLL patients. [ABSTRACT FROM AUTHOR]

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

At various times in recent decades, surges have occurred in optimism about the potential for universal influenza vaccines that provide strong, broad, and long-lasting protection and could substantially reduce the disease burden associated with seasonal influenza epidemics as well as the threat posed by pandemic influenza. Each year more than 500 million doses of seasonal influenza vaccine are administered around the world, with most doses being egg-grown inactivated subunit or split-virion vaccines. These vaccines tend to have moderate effectiveness against medically attended influenza for influenza A(H1N1) and influenza B, and somewhat lower for influenza A(H3N2) where differences between vaccine strains and circulating strains can occur more frequently due to antigenic drift and egg adaptations in the vaccine strains. Several enhanced influenza vaccine platforms have been developed including cell-grown antigen, the inclusion of adjuvants, or higher antigen doses, to improve immunogenicity and protection. During the COVID-19 pandemic there was unprecedented speed in development and roll-out of relatively new vaccine platforms, including mRNA vaccines and viral vector vaccines. These new platforms present opportunities to improve protection for influenza beyond existing products. Other approaches continue to be explored. Incremental improvements in influenza vaccine performance should be achievable in the short to medium term. [ABSTRACT FROM AUTHOR]

With the coming of the post‐antibiotic era, there is an increasingly urgent need for safe and efficient antibacterial vaccines. Bacterial outer membrane vesicles (OMVs) have received increased attention recently as a potential subunit vaccine. OMVs are non‐replicative and contain the principle immunogenic bacterial antigen, which circumvents the safety concerns of live‐attenuated vaccines. Here, we developed a novel nano‐vaccine by coating OMVs onto PEGylated nano‐Rehmannia glutinosa polysaccharide (pRL) in a structure consisting of concentric circles, resulting in a more stable vaccine with improved immunogenicity. The immunological function of the pRL‐OMV formulation was evaluated in vivo and in vitro, and the underlying mechanism was studied though transcriptomic analysis. The pRL‐OMV formulation significantly increased dendritic cell (DC) proliferation and cytokine secretion. Efficient phagocytosis of the formulation by DCs was accompanied by DC maturation. Further, the formulation demonstrated superior lymph node targeting, contributing to a potent mixed cellular response and bacterial‐specific antibody response against Bordetella bronchiseptica infection. Specifically, transcriptomic analysis revealed that the immune protection function correlated with T‐cell receptor signalling and Th1/Th2/Th17 differentiation, among other markers of enhanced immunological activity. These findings have implications for the future application of OMV‐coated nano‐carriers in antimicrobial immunotherapy. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study aimed to assess the reactogenicity and immunogenicity of various SARS-CoV-2 vaccines and compare their protective effects against COVID-19 among healthcare workers (HCWs) during the Omicron outbreak in Taiwan. Methods: Conducted from March 2021 to July 2023, this prospective observational study included healthy HCWs without prior COVID-19 immunization. Participants chose between adenovirus-vectored (AstraZeneca), mRNA (Moderna, BioNTech-Pfizer), and protein-based (Medigen, Novavax) vaccines. Blood samples were taken at multiple points to measure neutralizing antibody (nAb) titers, and adverse events (AEs) were recorded via questionnaires. Results: Of 710 HCWs, 668 (94.1%) completed three doses, and 290 (40.8%) received a fourth dose during the Omicron outbreak. AEs were more common with AstraZeneca and Moderna vaccines, while Medigen caused fewer AEs. Initial nAb titers were highest with Moderna but waned over time regardless of the vaccine. Booster doses significantly increased nAb titers, with the highest levels observed in Moderna BA1 recipients. The fourth dose significantly reduced COVID-19 incidence, with Moderna BA1 being the most effective. Conclusions: Regular booster doses, especially with mRNA and adjuvant-protein vaccines, effectively enhance nAb levels and reduce infection rates, providing critical protection for frontline HCWs during variant outbreaks. [ABSTRACT FROM AUTHOR]

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9–18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02–8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15–0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients. [ABSTRACT FROM AUTHOR]

(1) Background: Shift work can affect physical health and the immune system by altering the body's circadian rhythms. This study investigated the factors associated with the hepatitis B virus (HBV) vaccination response in manufacturing workers, classified by whether they engaged in shift work or not. (2) Methods: This retrospective observational study was conducted among adults employed at two manufacturing companies. Those with negative initial hepatitis B surface antibody (HBsAb) levels before vaccination and who subsequently received a three-dose series of HBV vaccine were enrolled. Hepatitis B surface antibodies were examined for 3 years after the first dose. The endpoint of this study was the failure of a seroprotective anti-HB response after vaccination (HBsAb < 10 mIU/mL). Binary logistic regression models were used to analyze factors associated with response failures. (3) Results: Of the 1103 eligible subjects, 337 (30.6%) were shift workers. The failure rate was numerically higher in the shift workers (9.2%) than in the non-shift workers (7.9%), without statistical significance (p = 0.405). However, after adjustment with the binary logistic regression models, the shift workers had a statistically significantly higher rate of response failures than the non-shift workers (odds ratio 2.87; 95% confidence interval 1.64–5.05, p < 0.001), as did males, older workers, those with a low initial anti-HB titer, those with a vitamin D deficiency, and current smokers. (4) Conclusions: Our findings suggest a possible association between shift work and the serologic responses to HBV vaccination. Novel strategies for vaccination should be considered for shift workers. [ABSTRACT FROM AUTHOR]

Seasonal influenza vaccine effectiveness is low. Carbohydrate fatty acid monosulphate ester (CMS), a new oil-in-water adjuvant, has proven potency in animal models with suggested capacity for dose-sparing. The objective was to evaluate safety and immunogenicity of CMS when added to a low-dose influenza vaccine (QIV) in humans. In a randomised, double-blind, active-controlled, first-in-human study, sixty participants (18–50 years) received either 0.5 mg CMS or 2 mg CMS with 1/5th dose QIV, or a full dose QIV without CMS. Adverse events (AE) were monitored until 7 days post-vaccination. Haemagglutinin inhibition (HI) titres in serum and CD4+ T cells in PBMCs were determined at day 0, 7, 28, and 180. Mean age was 37.6 (±10.1) years and 42/60 (70.0%) were female. Pain at injection site (42/60, 86.7%) and headache (34/60, 56.7%) were reported most and more frequently in the 2 mg CMS group. HI titres and the frequency of influenza specific CD4+ T cells were equal across strains for the three cohorts on all visits, increased until day 28 and decreased at day 180 to values higher than baseline. CMS was safe in humans. Humoral and cell-mediated immunogenicity was similar across vaccines, even with 1/5th antigen dose. CMS can have beneficial implications in low-resource settings or in a pandemic context. [ABSTRACT FROM AUTHOR]

We previously reported a reduced humoral immune response to the COVID-19 vaccines. Subsequently, we observed a lower susceptibility to COVID-19 in individuals carrying the ALDH2 rs671 variant through a web-based retrospective survey. Based on these findings, we hypothesized that rs671 variant was beneficial for cellular immunity against COVID-19. Using the IFN-γ enzyme-linked immunospot (ELISPOT) assay, we assessed cellular immunity before and after COVID-19 vaccination in two subcohorts of a previously reported cohort. Subcohort 1 (26 participants) had six repeated observations at baseline after one to three doses, whereas subcohort 2 (19 participants) had two observations before and after the third dose. ELISPOT counts at six months after the second dose increased from baseline in carriers of the rs671 variant but not in non-carriers. A positive effect of rs671 on ELISPOT counts was estimated using a mixed model (183 observations from 45 participants), including the random effect of subcohort, repeated measures, and fixed effects of vaccine type, age, sex, height, lifestyle, steroid use, and allergic disease. There was no association between ELISPOT counts and specific IgG levels, suggesting a limitation in estimating protective potential by humoral response. Our sequential observational studies suggest a beneficial effect of the rs671 variant in SARS-CoV-2 infection via enhanced cellular immune response, providing a potential basis for optimizing preventive measures and drug development. [ABSTRACT FROM AUTHOR]

A phase 1–2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382), with parallel groups, involving 1161 participants, was designed to assess the safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were a ≥4-fold anti-RBD IgG seroconversion or a ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe—no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headaches predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p < 0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints. [ABSTRACT FROM AUTHOR]

Several vaccines against chikungunya fever have been developed and tested, and one has been recently licensed. We performed a meta-analysis to estimate the immunogenicity and safety of all chikungunya vaccines that have been progressed to clinical trial evaluation (VLA1553; mRNA-1388/VAL-181388; PXVX0317/VRC-CHKVLP059-00-VP; ChAdOx1 Chik; MV-CHIK). We included trials retrieved from MedLine, Scopus, and ClinicalTrials.gov. The outcomes were the rates of seroconversion/seroresponse and serious adverse events (SAEs) after the primary immunization course. We retrieved a total of 14 datasets, including >4000 participants. All candidate chikungunya vaccines were able to elicit an immunogenic response in ≥96% of vaccinated subjects, regardless of the vaccination schedule and platform used, and the seroconversion/seroresponse rates remained high 6 to 12 months after vaccination for most vaccines. Four of the five candidate vaccines showed a good overall safety profile (no data were available for ChAdOx1 Chik), with no significant increase in the risk of SAEs among the vaccinated, and a low absolute risk of product-related SAEs. Overall, the present findings support the potential use of the candidate vaccines for the prevention of chikungunya and the current indication for use in adult travelers to endemic regions of the licensed VLA 1553 vaccine. In order to extend chikungunya vaccination to a wider audience, further studies are needed on individuals from endemic countries and frail populations. [ABSTRACT FROM AUTHOR]

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

Maternal vaccination is a safe and effective means of preventing infection in pregnant women, their fetuses, and infants after birth. Several vaccines are routinely administered in pregnancy as a valuable part of prenatal care with supporting recommendations from national and international health organizations. Fears concerning vaccine safety in pregnancy are pervasive despite sufficient available safety data to support their use, leading to underutilization of maternal immunization. Despite this hesitancy, the field of maternal vaccination is evolving to include more vaccines in the routine prenatal vaccination schedule, including the new RSV vaccine. This review discusses the currently recommended vaccines in pregnancy, evidence for their use, and an overview of ongoing clinical trials investigating prospective vaccines for pregnant women. [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

[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]

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

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

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

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

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

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

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

Background: Infectious diseases such as peste des petits ruminants (PPRs), contagious caprine pleuropneumonia (CCPP), sheep and goat pox (SGPX), and pasteurellosis have considerable impacts on the optimal utilization of sheep and goat resources in Ethiopia. Immunization using multiple vaccines administered simultaneously has been suggested as a cost-effective and safe approach to controlling and preventing these diseases. Aim: The aim of this study was to assess the immunogenicity and safety of multiple vaccines administered simultaneously in goats. Methods: Sero-negative PPR, CCPP, SGPX, and Pasteurellosis goats were immunized with multiple vaccines. Goats vaccinated with a single vaccine against each disease served as a positive control. The immune response of the goats was assessed using serological tests, and any adverse effects were monitored. Results: The results of the present study showed that goats vaccinated with multiple vaccines exhibited a remarkable immune response against PPR, CCPP, and pasteurellosis. In contrast, they did not produce a protective immune response against sheep or goat pox. No adverse effects were observed with any of the vaccines. Conclusion: This study suggested that combined vaccines can be effective at inducing a protective immune response in goats. However, further research is needed to fully understand the immune response to combined vaccines. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

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

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

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

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

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