Human Vaccines & Immunotherapeutics最新文献

France was the first country to grant Sipavibart (AZD3152, an investigational long-acting monoclonal antibody) as a COVID-19 pre-exposure prophylaxis treatment in immunocompromised individuals in December 2023. The first patients to receive Sipavibart had different profiles, but they were all highly immunocompromised with frequently associated hypogammaglobulinemia and other chronic conditions. No adverse event was reported.

Seasonal influenza is a severe disease that significantly impacts public health, causing millions of infections and hundreds of thousands of deaths each year. Seasonal influenza viruses, particularly the H3N2 subtype, exhibit high antigenic variability, often leading to mismatch between vaccine strains and circulating strains. Therefore, rapidly assessing the alignment between existing seasonal influenza vaccine and circulating strains is crucial for enhancing vaccine efficacy. This study, based on a pseudovirus platform, evaluated the match between current influenza H3N2 vaccine strains and circulating strains through cross-neutralization assays using clinical human immune sera against globally circulating influenza virus strains. The research results show that although mutations are present in the circulating strains, the current H3N2 vaccine strain still imparting effective protection, providing a scientific basis for encouraging influenza vaccination. This research methodology can be sustainably applied for the neutralization potency assessment of subsequent circulating strains, establishing a persistent methodological framework.

The COVID-19 pandemic disproportionately affected racial and ethnic minority communities across the United States (U.S.). Despite the disproportionate burden of COVID-19 faced by communities of color, Black and Hispanic communities are less likely to be fully vaccinated than White non-Hispanic Persons. Health inequity and vaccine hesitancy are complex phenomena that require multilevel responses tailored to the unique needs of each community, a process that inherently necessitates a high level of community engagement in order to develop the most effective health interventions. Building on the principles of community based participatory research (CBPR) and with the support of the National Institutes of Health (NIH), Project 2VIDA! was born. A multidisciplinary collaborative of academic researchers, community members, and clinicians whose aim is to foster sustainable partnerships to reduce the burden of COVID-19 in Hispanic and Black communities across Southern California. Our model was designed to meet our community members where they were - whether on their lunch break or picking their children from school. This CBPR model has been well received by community members. Future health interventions focused on reducing health disparities should prioritize the role of the community, leverage the voices of key community partners, and be grounded in equitable power sharing.

Staphylococcal Enterotoxin B (SEB), produced by Staphylococcus aureus (S. aureus), is a powerful superantigen that induces severe immune disruption and toxic shock syndrome (TSS) upon binding to MHC-II and TCR. Despite its significant impact on the pathogenesis of S. aureus, there are currently no specific therapeutic interventions available to counteract the mechanism of action exerted by this toxin. In this study, we have identified a human monoclonal antibody, named Hm0487, that specifically targets SEB by single-cell sequencing using PBMCs isolated from volunteers enrolled in a phase I clinical trial of the five-antigen S. aureus vaccine. X-ray crystallography studies revealed that Hm0487 exhibits high affinity for a linear B cell epitope in SEB (SEB_138-147), which is located distantly from the site involved in the formation of the MHC-SEB-TCR ternary complex. Furthermore, in vitro studies demonstrated that Hm0487 significantly impacts the interaction of SEB with both receptors and the binding to immune cells, probably due to an allosteric effect on SEB rather than competing with receptors for binding sites. Moreover, both in vitro and in vivo studies validated that Hm0487 displayed efficient neutralizing efficacy in models of lethal shock and sepsis induced by either SEB or bacterial challenge. Our findings unveil an alternative mechanism for neutralizing the pathogenesis of SEB by Hm0487, and this antibody provides a novel strategy for mitigating both SEB-induced toxicity and S. aureus infection.

Meningococcal vaccination strategies in China are intricate, including multiple vaccines targeting different serogroups. The current National Immunization Program (NIP) includes two polysaccharide vaccines for serogroups A and C (MPV-A and MPV-AC), covering limited serogroups and requiring adaptation. This study aims to evaluate the cost-effectiveness of replacing the current strategy with alternative strategies utilizing non-NIP vaccines to inform policy decisions. From a societal perspective, a decision tree-Markov model was constructed to simulate the economic and health consequences of meningococcal disease in a 2019 birth cohort with four vaccination strategies. Epidemiology, vaccine efficacy, cost, and other parameters were derived from previous studies. We conducted sensitivity analyses to assess the robustness of the findings and explored prices for non-NIP vaccines that enable cost-effective strategies. Compared to the current strategy, alternative strategies using quadrivalent polysaccharide vaccine (MPV-4), bivalent conjugate vaccine (MCV-AC), and quadrivalent conjugate vaccine (MCV-4) could avoid 91, 286, and 455 more meningococcal cases. The ICERs were estimated at approximately $250 thousand/QALY, $450 thousand/QALY, and $1.5 million/QALY, all exceeding the threshold of three times GDP per capita. The alternative strategies were not cost-effective. However, if vaccine prices were reduced to $3.9 for MPV-4, $9.9 for MCV-AC, and $12 for MCV-4, the corresponding strategy would be cost-effective. The current meningococcal vaccination strategy in China could effectively prevent the disease at a low cost, but with limited serogroup coverage. Strategies using MPV-4, MCV-AC, or MCV-4 could increase health benefits at a substantial cost, and might become cost-effective if vaccine prices decrease.

Monoclonal neutralizing antibodies (mAbs) are considered an important prophylactic against SARS-CoV-2 infection in at-risk populations and a strategy to counteract future sarbecovirus-induced disease. However, most mAbs isolated so far neutralize only a few sarbecovirus strains. Therefore, there is a growing interest in bispecific antibodies (bsAbs) which can simultaneously target different spike epitopes and thereby increase neutralizing breadth and prevent viral escape. Here, we generate and characterize a panel of 30 novel broadly reactive bsAbs using an efficient controlled Fab-arm exchange protocol. We specifically combine some of the broadest mAbs described so far, which target conserved epitopes on the receptor binding domain (RBD). Several bsAbs show superior cross-binding and neutralization compared to the parental mAbs and cocktails against sarbecoviruses from diverse clades, including recent SARS-CoV-2 variants. BsAbs which include mAb COVA2-02 are among the most potent and broad combinations. As a result, we study the unknown epitope of COVA2-02 and show that this mAb targets a distinct conserved region at the base of the RBD, which could be of interest when designing next-generation bsAb constructs to contribute to a better pandemic preparedness.

Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO₄ as an adjuvant. The AH vaccine was constructed by fusing Als3_17-432 and Hyr1_25-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO₄, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine's efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO₄ combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO₄ vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.

To evaluate the performance of "Vaccination Rates Monitoring Report System" implemented by Shenzhen CDC, we conducted an analysis of the data quality and identify key areas for system improvement. Following evaluation guidelines provided by WHO and United States CDC, we established six evaluation attributes: representativeness, simplicity, acceptability, data reliability, stability and timeliness. In eastern, central and western regions of Shenzhen, we selected one district from each region, of which the local CDC and ten CHSCs under jurisdiction were chosen for evaluation. On-site inspections, questionnaires survey and interviews were utilized for data collection, while the Likert scale method was used for attributes rating evaluation. A total of 70 participants were surveyed, consisting of 60 CHSCs and 10 CDCs staff. The gender ratio was 1:2.5 (males to females), with the majority falling within the 25-34 age range (46%). Most participants held full-time positions (80%) and had more than 5 years of work experience (62%). The system achieved 100% coverage of all CHSCs and CDCs (100%). The cumulative percentage scores for the overall favorable options of simplicity, acceptability, data reliability, stability, and timeliness were 79%, 85%, 73%, 50%, and 71% respectively. The system operates normally with strong representativeness. Acceptability was rated as "good." Simplicity, data reliability, and system timeliness were rated as "average," while system stability was rated as "poor." Based on these survey results, developers should urgently investigate reasons for poor stability, particularly addressing concerns from CHSCs users. Additionally, the issues and shortcomings identified in other attributes should also be gradually improved.