Immunology of vaccine adjuvants enhancing respiratory viral vaccine efficacy

Abstract

Abstract We investigated the adjuvant effects of MPL (TLR4 agonist) and CpG (TLR9 agonist) on promoting protection after vaccination of C57BL/6 and BALB/c mice with inactivated influenza split virus or human respiratory syncytial virus (RSV) vaccines. Adjuvant effects of combination MPL and CpG (MPL+CpG) on improving protective vaccine efficacy were evident by higher levels of protective humoral and cellular immune responses to vaccination, more effective control of lung viral replication, prevention of weight loss, and inflammatory cytokines and cellular infiltrates in vaccinated mice after virus challenge. Vaccine-enhanced respiratory disease, a well-known phenomenon due to atypical immune priming by RSV vaccination after challenge, could be prevented by MPL + CpG adjuvants in RSV vaccination, shaping toward Th1 and IgG2a isotype immune responses. In contrast, aluminum hydroxide and squalene oil-in-water adjuvants (AddaVax) were not effective in conferring vaccine-induced protection against influenza and RSV in BALB/c mice after vaccination and challenge. Combination of MPL and CpG was found to exhibit distinct effects on modulating inflammatory micro-environment with cytokines, chemokines, and innate infiltrates in vivo within a day as well as stimulating dendritic cells in vitro to secrete IL-12p70 and TNF-α cytokines. In summary, the findings suggest that a combination adjuvant of different TLR agonists exhibits a unique pattern of innate and adaptive immune responses, contributing to protection by inactivated influenza split virus and subunit RSV vaccination.