Effect on Cellular and Humoral Immune Responses of the AS03 Adjuvant System in an A/H1N1/2009 Influenza Virus Vaccine Administered to Adults during Two Randomized Controlled Trials
Abstract
Effect on Cellular and Humoral Immune Responses of the AS03 Adjuvant System in an A/H1N1/2009 Influenza Virus Vaccine Administered to Adults during Two Randomized Controlled Trials ▿ † François Roman 1 , Frédéric Clément 2 , Walthère Dewé 1 , Karl Walravens 3 , Cathy Maes 2 , Julie Willekens 2 , Fien De Boever 2 , Emmanuel Hanon 1 and Geert Leroux-Roels 2 , * 1 GlaxoSmithKline Biologicals, Wavre, Belgium 2 Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium 3 GlaxoSmithKline Biologicals, Rixensart, Belgium ABSTRACT The influence of AS03 A , a tocopherol oil-in-water emulsion-based adjuvant system, on humoral and cell-mediated responses to A/California/7/2009 H1N1 pandemic vaccine was investigated. In two observer-blind studies, a total of 261 healthy adults aged 18 to 60 years were randomized to receive either AS03 A -adjuvanted H1N1 vaccine containing 3.75 μg hemagglutinin (HA) or nonadjuvanted H1N1 vaccine containing 15 or 3.75 μg HA on days 0 and 21. Hemagglutination inhibition (HI) antibody and T-cell responses were analyzed up to day 42. A first dose of AS03 A -adjuvanted vaccine (3.75 μg HA) or nonadjuvanted vaccine (15 μg HA) induced HI responses of similar magnitudes that exceeded licensure criteria (e.g., 94 to 100% with titers of ≥40). A lower response following 3.75 μg HA without adjuvant was observed (73% with titers of ≥40). Following a second dose, geometric mean HI titers at day 42 were higher for AS03 A -adjuvanted vaccine (636 and 637) relative to nonadjuvanted vaccine (341 for 15 μg HA and 150 for 3.75 μg HA). Over the 42-day period, the increase in frequency of A/H1N1/2009-specific CD4 + T cells was significantly higher in the adjuvanted group than in the nonadjuvanted group. There was no evidence of correlation between baseline CD4 + T-cell frequencies and day 21 HI antibody titers, while there was some correlation ( R = 0.35) between day 21 CD4 + T-cell frequencies and day 42 HI titers. AS03 A adjuvant enhanced the humoral and CD4 + T-cell-mediated responses to A/H1N1/2009 vaccine. Baseline A/H1N1/2009-specific CD4 + T-cell frequencies did not predict post-dose 1 antibody responses, but there was some correlation between post-dose 1 CD4 + T-cell frequencies and post-dose 2 antibody responses.