Abstract
Differences in innate immune ‘imprinting’ between vaccine adjuvants may mediate dissimilar effects on the quantity/quality of persisting adaptive responses. We compared antibody avidity maturation, antibody/memory B cell/CD4+ T cell response durability, and recall responses to non-adjuvanted fractional-dose antigen administered 1-year post-immunization (Day [D]360), between hepatitis B vaccines containing Adjuvant System (AS)01B, AS01E, AS03, AS04, or Alum (NCT00805389). Both the antibody and B cell levels ranked similarly (AS01B/E/AS03 > AS04 > Alum) at peak response, at D360, and following their increases post-antigen recall (D390). Proportions of high-avidity antibodies increased post-dose 2 across all groups and persisted at D360, but avidity maturation appeared to be more strongly promoted by AS vs. Alum. Post-antigen recall, frequencies of subjects with high-avidity antibodies increased only markedly in the AS groups. Among the AS, total antibody responses were lowest for AS04. However, proportions of high-avidity antibodies were similar between groups, suggesting that MPL in AS04 contributes to avidity maturation. Specific combinations of immunoenhancers in the AS, regardless of their individual nature, increase antibody persistence and avidity maturation.
Highlights
Protection against many infectious diseases is mediated by a functional, persistent antibody response, which is a critical immune correlate for many licensed human vaccines
Subjects received two doses of hepatitis B surface antigen (HBsAg) vaccine adjuvanted with AS01B, AS01E, AS03, AS04, or Alum, at D0 and D3021
To investigate memory ences between groups may be consistent with our hypothesis that, due to dissimilar innate signals provided to CD4+ T cells by the adjuvanted vaccines, the different levels of T cell help received by memory B cells result in short-lived plasma cells (PCs) with diverging qualities, for example in terms of affinity maturation[11,23]
Summary
Protection against many infectious diseases is mediated by a functional, persistent antibody response, which is a critical immune correlate for many licensed human vaccines. The level of antigen–antibody binding avidity, a qualitative response index, can correlate with protection. This has been demonstrated for the RTS, S malaria vaccine, amongst others, and for several monoclonal antibodies (mAb) treatments[3,4]. Inadequate levels of avidity maturation (the latter defined as the increase of avidity over time) can heighten susceptibility to viral infection, as seen for mumps vaccines[6]. Both quantitative and qualitative yardsticks can determine vaccine efficacy
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