Abstract
During the 2009–2010 influenza pandemic, an adjuvanted, dose-sparing vaccine was recommended for most Canadians. We hypothesize that differences exist in the responses to AS03-adjuvanted, low antigen (Ag) dose versus unadjuvanted, full-dose vaccines. We investigated the relationship between Ag dose and the oil-in-water emulsion Adjuvant System AS03. BALB/c mice received two IM doses of AS03A or AS03B with exaggerated dilutions of A/Uruguay/716/2007 H3N2 split virion vaccine Ag. Immune responses were assessed 3 weeks after the booster. Unadjuvanted “high” (3 μg) and low-dose (0.03–0.003 μg) vaccines generated similar serum antibody titers and cytokine secretion patterns in restimulated splenocytes. Compared to unadjuvanted “high-dose” vaccination, both AS03A and AS03B-adjuvanted low-dose vaccines tended to elicit higher serum antibody titers, broader induction of cytokine secretion and generated more influenza-specific antibody secreting cells and cytokine-secreting CD4 and CD8 T cells in splenocytes. We show that varying Ag and/or AS03 dose in this influenza vaccination mouse model can strongly influence both the magnitude and pattern of the immune response elicited. These findings are highly relevant given the likelihood of expanded use of adjuvanted, dose-sparing vaccines and raise questions about the use of “standard” doses of vaccines in pre-clinical vaccine studies.
Highlights
Vaccines are the most cost-effective method to prevent influenza virus-associated morbidity and mortality [1]; they are least effective in high-risk populations [1]
AS03-adjuvanted vaccines were able to generate superior humoral responses and distinct cellular immune responses compared to unadjuvanted vaccine
We demonstrate that use of AS03 can markedly change both the magnitude and pattern of vaccine-induced humoral and cellular immune responses in mice
Summary
Vaccines are the most cost-effective method to prevent influenza virus-associated morbidity and mortality [1]; they are least effective in high-risk populations [1]. During the 2009–2010 A/California pandemic H1N1 influenza outbreak, the World Health Organization recommended the use of antigen (Ag)-sparing vaccines [2]. In Canada, an Ag-sparing vaccine formulated with AS03 and 25% of the adult hemagglutinin (HA) dose in unadjuvanted seasonal influenza vaccines was selected for administration to the majority of Canadians (ArepanrixTM; GSK Vaccines, Mississauga, ON, Canada) [3]. A similar vaccine was used in Europe (PandemrixTM, GSK Vaccines, Rixensart, Belgium)
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