Characterization of splenic and systemic immunity by differentially charged lipid adjuvants in enhancing post-intranasal immunization response against influenza

Abstract

Abstract Background: At this time when vaccine development is at its peak against different respiratory diseases, it is of utmost importance to find suitable adjuvants that can increase the potency of the vaccine candidates. This study aims to find the systemic and splenic immune mechanism exhibited in mice models by anionic and cationic lipid adjuvants in presence of vaccine-candidate influenza antigen Hemagglutinin (HA). Results: The study demonstrates how anionic and cationic lipid adjuvants can differ in their mechanism to induce immune protection. In presence of HA antigen, the cationic adjuvant (N3) induces enhanced dendritic cell activity, MHCI, CD80-CD86 costimulatory marker expression with significantly higher CD8T and Th17 population with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Anionic adjuvant (L3) induces significantly higher MHCII and DEC205 expression on dendritic cells with significantly increased CD4T and regulatory T cell population. This L3 treatment group also exhibited a higher plasma B cell population with significantly higher antigen-specific IgG and IgA titer with virus neutralization potential. Conclusion: Thus, in this study, we illustrate how the use of differentially charged lipid adjuvants in combination with influenza HA antigen, drives differential adaptive immune response patterns. While anionic adjuvants are significantly higher humoral responses than cationic adjuvants, the latter influence significantly higher Th1/Th17 response. It is much more difficult to find a suitable and safer candidate vaccine antigen than to simply alter the associated adjuvant for a customized vaccination program. This will pave the way forward in the selection of the adjuvants based on their charges in boosting specific immune response arms in the future development of vaccine formulation.