Development of inactivated subunit influenza vaccine endowing with IgA induction and protection against heterologous strain

Abstract

Abstract Vaccination is known to be the best way to prevent and control seasonal influenza infections. Among the various available influenza vaccines, an inactivated vaccine shows improved protective effects associated with greater safety. However, since the influenza virus is continuously evolving, its response to inactivated vaccines becomes increasingly difficult to predict, leading to complete or partial loss of protection against the virus. In addition, immunogenicity is lower than other types and Th2-biased immune responses have been reported. In this study, we have investigated the role of the single-stranded RNA (ssRNA) adjuvant derived from the intergenic region of internal ribosome entry site of Cricket Paralysis virus in seasonal inactivated subunit influenza vaccine (ISIV). We found that the ssRNA adjuvant stimulated balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and HI) responses, along with mucosal (indicated by IgA) immune response. Moreover, the ssRNA adjuvant formulated ISIV enhanced viral clearance and improved lung pathology after homologous and even heterologous influenza virus infections. The proportion of memory CD4+ and CD8+ T cells, important for long term immunity, was also observed to increase. Therefore, the ssRNA adjuvant formulated ISIV is effective in inducing humoral and cellular immune responses, cross protection, and long-term immunity.