Systems serology-based comparison of antibody effector functions induced by adjuvanted vaccines to guide vaccine design

The mechanisms by which antibodies confer protection vary across vaccines, ranging from simple neutralization to functions requiring innate immune recruitment via Fc-dependent mechanisms. The role of adjuvants in shaping the maturation of antibody-effector functions remains under investigated. Using systems serology, we compared adjuvants in licensed vaccines (AS01(B)/AS01(E)/AS03/AS04/Alum) combined with a model antigen. Antigen-naive adults received two adjuvanted immunizations followed by late revaccination with fractional-dosed non-adjuvanted antigen (NCT00805389). A dichotomy in response quantities/qualities emerged post-dose 2 between AS01(B)/AS01(E)/AS03 and AS04/Alum, based on four features related to immunoglobulin titers or Fc-effector functions. AS01(B/E) and AS03 induced similar robust responses that were boosted upon revaccination, suggesting that memory B-cell programming by the adjuvanted vaccinations dictated responses post non-adjuvanted boost. AS04 and Alum induced weaker responses, that were dissimilar with enhanced functionalities for AS04. Distinct adjuvant classes can be leveraged to tune antibody-effector functions, where selective vaccine formulation using adjuvants with different immunological properties may direct antigen-specific antibody functions.