Vaccination against influenza viruses suffers from low efficacy in conferring homologous and cross-protection, particularly in older adults. Here, we compared the effects of three different adjuvant types (QS-21+MPL, CpG+MPL and bacterial cell wall CWS) on enhancing the immunogenicity and homologous and heterosubtypic protection of influenza vaccination in young adult and aged mouse models. A combination of saponin QS-21 and monophosphoryl lipid A (QS-21+MPL) was most effective in inducing T helper type 1 (Th1) T cell and cross-reactive IgG as well as hemagglutination inhibiting antibody responses to influenza vaccination. Both combination adjuvants (QS-21+MPL and CpG+MPL) exhibited high potency by preventing weight loss and reducing viral loads and enhanced homologous and cross-protection by influenza vaccination in adult and aged mouse models. Bacillus Calmette-Guerin cell-wall skeleton (CWS) displayed substantial adjuvant effects on immune responses to influenza vaccination but lower adjuvant efficacy in inducing Th1 IgG responses, cross-protection in adult mice, and in conferring homologous protection in aged mice. This study has significance in comparing the effects of potent adjuvants on enhancing humoral and cellular immune responses to influenza virus vaccination, inducing homologous and cross-protection in adult and aged populations.
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