Author Correction: SPA14 liposomes combining saponin with fully synthetic TLR4 agonist provide adjuvanticity to hCMV vaccine candidate
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Calboxyvinyl polymer adjuvant enhances respiratory iga responses through mucosal and systemic administration
Adjuvants play a crucial role in enhancing vaccine efficacy. Although several adjuvants have been approved, there remains a demand for safer and more effective adjuvants for nasal vaccines. Here, we identified calboxyvinyl polymer (CVP) as a superior mucosal vaccine adjuvant from pharmaceutical base materials using our screening systems; single nasal vaccination of the CVP-combined influenza split vaccine-induced antigen-specific IgA and IgG antibodies and provided protection against lethal influenza virus infection. Furthermore, nasal vaccination with CVP-combined severe acute respiratory syndrome coronavirus 2 antigen protected against the virus and stimulated the production of highly cross-reactive IgG antibodies against variants XBB1.5 and JN.1. Intriguingly, intramuscular vaccination of the CVP-combined vaccine also elicited the production of IgA antibodies in both nasal wash and bronchoalveolar lavage fluid in mice and cynomolgus monkeys. CVP therefore offers superior adjuvanticity to existing adjuvants and is anticipated to be a safe and effective adjuvant for mucosal vaccines.
Identifying falsified COVID-19 vaccines by analysing vaccine vial label and excipient profiles using MALDI-ToF mass spectrometry
The rapid development and worldwide distribution of COVID-19 vaccines is a remarkable achievement of biomedical research and logistical implementation. However, these developments are associated with the risk of a surge of substandard and falsified (SF) vaccines, as illustrated by the 184 incidents with SF and diverted COVID-19 vaccines which have been reported during the pandemic in 48 countries, with a paucity of methods for their detection in supply chains. In this context, matrix-assisted laser desorption ionisation-time of flight (MALDI-ToF) mass spectrometry (MS) is globally available for fast and accurate analysis of bacteria in patient samples, offering a potentially accessible solution to identify SF vaccines. We analysed the COVISHIELD™ COVID-19 vaccine; falsified versions of which were found in India, Myanmar and Uganda. We demonstrate for the first time that analysis of spectra from the vaccine vial label and its adhesive could be used as a novel approach to detect falsified vaccines. Vials tested by this approach could be retained in the supply chain since it is non-invasive. We also assessed whether MALDI-ToF MS could be used to distinguish the COVISHIELD™ vaccine from surrogates of falsified vaccines and the effect of temperature on vaccine stability. Both polysorbate 80 and L-histidine excipients of the genuine vaccine could be detected by the presence of a unique combination of MALDI-ToF MS peaks which allowed us to distinguish between the genuine vaccines and falsified vaccine surrogates. Furthermore, even if a falsified product contained polysorbate 80 at the same concentration as used in the genuine vaccine, the characteristic spectral profile of polysorbate 80 used in genuine products is a reliable internal marker for vaccine authenticity. Our findings demonstrate that MALDI-ToF MS analysis of extracts from vial labels and the vaccine excipients themselves can be used independently to detect falsified vaccines. This approach has the potential to be integrated into the national regulatory standards and WHO’s Prevent, Detect, and Respond strategy as a novel effective tool for detecting falsified vaccines.
A recombinant protein vaccine induces protective immunity against SARS-CoV-2 JN.1 and XBB-lineage subvariants
The emergence of XBB- and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations. In addition, the unfavorable impacts of immune imprinting, stemming from continuous exposure to antigens from circulated viruses, have been observed to incline immune response against earlier lineages, thereby declining the neutralization to newly emerged Omicron subvariants. In response to this, the advancement of next-generation vaccines against COVID-19 targeting components from new subvariants such as XBB-lineage is imperative. In the current study, a self-assembled trimeric recombinant protein (RBDXBB.1.5-HR) was generated by concatenating the sequences of the receptor binding domain (RBD) derived from XBB.1.5 with heptad-repeat 1 (HR1) and HR2 sequences from the spike S2 subunit. Adjuvanted-RBDXBB.1.5-HR induced robust humoral and cellular immune responses, characterized by elevated neutralization against JN.1-inculuded subvariants and a substantial population of antigen-specific T memory cells. Protective immunity conferred by RBDXBB.1.5-HR vaccine was preserved post-immunization, as evidenced by germinal center B (GC B) and T follicular helper (Tfh) responses, sustained neutralization potency, and an increase in memory B cells (MBCs) and long-lived plasma cells (LLPCs). The RBDXBB.1.5-HR vaccine showed a favorable boosting effect when administered heterologously after three doses of inactivated virus (IV) and mRNA vaccines. Significantly, it provided protection against live Omicron EG.5.1 viruses in vivo. The monovalent RBDXBB.1.5-HR vaccine showed favorable safety and immunogenicity, boosting neutralizing antibodies against JN.1- and XBB-lineage subvariants in individuals with prior COVID-19 vaccinations. These findings highlight its clinical potential in safeguarding against circulating Omicron subvariants.
Optimizing rabies mRNA vaccine efficacy via RABV-G structural domain screening and heterologous prime-boost immunization
mRNA vaccine has become a promising technology platform for rabies prevention. This study explores the roles of different structural domains of rabies virus glycoprotein (RABV-G) and heterologous prime-boost strategies for enhanced immune responses and protection. The results suggested that mRNA vaccines encoding full-length RABV-G (RABV-Full) and RABV-R333Q induced strong immune responses and provided full protection against rabies, while mRNA vaccines encoding ectodomain/transmembrane domain (RABV-TE) and ectodomain (RABV-E) were less effective. Heterologous immunization results revealed that mRNA-primed strategies yielded higher long-lasting VNTs, but lower early VNTs than inactivated rabies virus (IRV)-primed strategies. 2×RABV-Full and IRV > RABV-Full provided 100% protection, while that of RABV-Full>IRV was 90%. Transcriptome analysis showed that rabies mRNA vaccine induced both MHCI and MHCII antigen presentation, as well as B/T cell activation. In conclusion, full-length RABV-G mRNA vaccines, particularly with an ‘IRV prime and RABV-Full boost’ strategy, hold great potential for rabies prevention.
Toll-like receptor response to Zika virus infection: progress toward infection control
Infection with the Zika virus (ZIKV) poses a threat to human health. An improved understanding of the host Toll-like receptor response, disease onset, and viral clearance in vivo and in vitro may lead to the development of therapeutic or prophylactic interventions against viral infections. Currently, no clinically approved ZIKV vaccine is available, highlighting the need for its development. In this study, we discuss the progress in the Zika vaccine, including advances in the use of Toll-like receptor agonists as vaccine adjuvants to enhance vaccine efficacy.
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