Abstract
There is an unmet need for new influenza vaccine strategies that compensate for impaired vaccine responses in elderly individuals. Here, we evaluated the effectiveness of a single-stranded RNA (ssRNA) as an adjuvant to enhance the efficacy of inactivated influenza vaccine (IIV) in mouse models. Immunization with the ssRNA along with IIV reduced viral titers as well as pathological and inflammatory scores in the lungs after influenza challenge in aged mice. ssRNA induced balanced Th1/Th2 responses with an increase in IgA titers. Moreover, the ssRNA adjuvant markedly increased the frequency of influenza HA-specific T cells and IFN-γ production along with the expression of genes related to innate and adaptive immune systems that could overcome immunosenescence in aged mice. Our findings indicate that ssRNA is an efficient vaccine adjuvant that boosts cellular and humoral immunity in aged mice, demonstrating its potential as a novel adjuvant for currently available influenza virus vaccines for elderly individuals.
Highlights
There is an unmet need for new influenza vaccine strategies that compensate for impaired vaccine responses in elderly individuals
We previously developed a novel single-stranded RNA platform that originated from cricket paralysis virus (CrPV) internal ribosome entry sites (IRES)
inactivated influenza vaccine (IIV) formulated with single-stranded RNA (ssRNA) induces a balanced IgG1/IgG2a immune response and elicits the production of higher neutralizing antibody titers in young and aged mice
Summary
There is an unmet need for new influenza vaccine strategies that compensate for impaired vaccine responses in elderly individuals. The ssRNA adjuvant markedly increased the frequency of influenza HA-specific T cells and IFN-γ production along with the expression of genes related to innate and adaptive immune systems that could overcome immunosenescence in aged mice. Vaccination is the most efficacious method to prevent the development of infectious diseases, the responsiveness of influenza vaccine is markedly reduced in elderly individuals owing to the occurrence of immunological aging[4,5]. Higher levels of several pro-inflammatory cytokines, chemokines, and C-reactive protein were detected both within the tissue microenvironments and in blood of aged individuals[13] This phenomenon is regarded as an obstacle for the induction of proper immune responses to pathogens or vaccines because it impedes the organism’s ability to recognize stimuli. Aged individuals may need higher threshold levels to activate immune cells than that of young individuals[14,15]
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