NPJ Vaccines最新文献

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.

Chlamydia trachomatis infections are the most common bacterial STIs globally and can lead to serious morbidity if untreated. Development of a killed, whole-cell vaccine has been stymied by coincident epitope destruction during inactivation. Here, we present a prototype Chlamydia vaccine composed of elementary bodies (EBs) from the related mouse pathogen, Chlamydia muridarum (Cm). EBs inactivated by gamma rays (Ir-Cm) in the presence of the antioxidant Mn²⁺-Decapeptide (DEHGTAVMLK) Phosphate (MDP) are protected from epitope damage but not DNA damage. Cm EBs gamma-inactivated with MDP retain their structure and provide significant protection in a murine genital tract infection model. Mice vaccinated with Ir-Cm (+MDP) exhibited elevated levels of Cm-specific IgG and IgA antibodies, reduced bacterial burdens, accelerated clearance, and distinctive cytokine responses compared to unvaccinated controls and animals vaccinated with EBs irradiated without MDP. Preserving EB epitopes with MDP during gamma inactivation offers the potential for a polyvalent, whole-cell vaccine against C. trachomatis.

We report SARS-CoV-2 KP.1, KP.1.1, KP.2 and KP.3 neutralizing antibody titers. They displayed increased immune evasion compared to JN.1, especially KP.1 and KP.3, for participants who experienced BF.7/BA.5.2 breakthrough infection or received bivalent (delta/BA.5) vaccine boosting. Second XBB sub-variants breakthrough infection enhanced the neutralization responses. HK.3-JN.1 RBD-heterodimer induced balanced and potent neutralizing responses against recently-circulating SARS-CoV-2 sub-variants in mice, supporting to replace the COVID-19 antigen containing JN.1 or its sub-variants.

Acute kidney injury (AKI) has been noticed after both COVID-19 vaccination and infection, affecting risk-benefit evaluations and vaccine hesitancy. We conducted a large-scale N3C cohort study to compare AKI incidence following COVID-19 vaccination and infection. Participants from December 2020 to August 2023 were divided into two groups based on their initially observed COVID-19 antigen exposure: COVID-19 vaccination group (n = 2,953,219) and COVID-19 infection group (n = 3,616,802). AKI was defined by diagnostic codes and serum creatinine changes within a 30 day follow-up window after exposure. The absolute risk of AKI was 0.66% in the vaccination group versus 4.88% in the infection group. After adjusting for various confounders, COVID-19 infection was associated with a significantly higher risk of AKI than COVID-19 vaccination (aHR = 10.31, P < 0.001). Our study reveals that COVID-19 vaccination is associated with a significant lower AKI risk compared to COVID-19 infection.

Rotaviruses pose a significant threat to young children. To identify novel pro- and anti-rotavirus host factors, we performed genome-wide CRISPR/Cas9 screens using rhesus rotavirus and African green monkey cells. Genetic deletion of either SERPINB1 or TMEM236, the top two antiviral factors, in MA104 cells increased virus titers in a rotavirus strain independent manner. Using this information, we optimized the existing rotavirus reverse genetics systems by combining SERPINB1 knockout MA104 cells with a C3P3-G3 helper plasmid. We improved the recovery efficiency and rescued several low-titer rotavirus reporter and mutant strains that prove difficult to rescue otherwise. Furthermore, we demonstrate that TMEM236 knockout in Vero cells supported higher yields of two live-attenuated rotavirus vaccine strains than the parental cell line and represents a more robust vaccine-producing cell substrate. Collectively, we developed a third-generation optimized rotavirus reverse genetics system and generated gene-edited Vero cells as a new substrate for improving rotavirus vaccine production.

Infectious diseases remain a persistent public health problem and a leading cause of morbidity and mortality in both humans and animals. The most effective method of combating viral infections is the widespread use of prophylactic vaccinations, which are administered to both people at risk of disease and animals that may serve as significant sources of infection. Therefore, it is crucial to develop technologies for the production of vaccines that are highly effective, easy to transport and store, and cost-effective. The protein expression system based on the protozoan Leishmania tarentolae offers several advantages, validated by numerous studies, making it a good platform for producing vaccine antigens. This review provides a comprehensive overview into the potential applications of L. tarentolae for the safe production of effective viral antigens.

This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

In August 2023, FDA approved Abrysvo for active immunization of pregnant individuals at 32 through 36 weeks gestational age to prevent lower respiratory tract disease (LRTD), including severe LRTD, caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age. A pragmatic approach to narrow the interval of use of Abrysvo in pregnant individuals balanced benefits of vaccine effectiveness against potential risks to infant and mother.

The absence of validated correlates of protection (CoPs) hampers the rational design and clinical development of new tuberculosis vaccines. In this review, we provide an overview of the potential CoPs in tuberculosis vaccine research. Major hindrances and potential opportunities are then discussed. Based on recent progress, it is reasonable to anticipate that success in the ongoing efforts to identify CoPs would be a game-changer in tuberculosis vaccine development.

Vaccines have played a central role in combating the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants are increasingly evading first-generation vaccine protection. To address this challenge, we designed "single-cycle infection SARS-CoV-2 viruses" (SCVs) that lack essential viral genes, possess distinctive immune-modulatory features, and exhibit an excellent safety profile in the Syrian hamster model. Animals intranasally vaccinated with an Envelope-gene-deleted vaccine candidate were fully protected against an autologous challenge with the SARS-CoV-2 virus through systemic and mucosal humoral immune responses. Additionally, the deletion of immune-downregulating viral genes in the vaccine construct prevented challenge virus transmission to contact animals. Moreover, vaccinated animals displayed neither tissue inflammation nor lung damage. Consequently, SCVs hold promising potential to induce potent protection against COVID-19, surpassing the immunity conferred by natural infection, as demonstrated in human immune cells.