Immunogenicity of Unadjuvanted and AF03-Adjuvanted A/H1N1/California/07/2009 Influenza Vaccines in Naïve and Influenza-Primed Mice

Abstract

Listen

Translate article

Influenza A virus of swine origin caused the first pandemic of the 21st century. In accordance with WHO recommendations, pandemic influenza vaccines were manufactured using the A/California/07/2009 (H1N1) strain and these vaccines were first evaluated in preclinical studies.We evaluated the immunogenicity of the A/California/07/2009 (H1N1) vaccine in both naïve and influenza-primed mice. Animals were intramuscularly-immunized on D0 and D21 with 0.3 or 3μg of hemagglutinin administered with or without AF03 adjuvant. Immunogenicity of the various formulations was compared to that of other seasonal H1N1 and H5N1 strains. Additionally, we investigated the impact of prior or concomitant immunization with seasonal trivalent inactivated influenza vaccine (TIV). The immune response was assessed by hemagglutination inhibition and microneutralization assays.In naïve mice, a single dose of unadjuvanted A/H1N1/California/07/2009 vaccine elicited HI titers>40, and a second vaccine dose strongly increased these titers. In the presence of AF03, even a low vaccine dosage elicited high antibody titers (HI titers>700). The antibody responses induced by both unadjuvanted and adjuvanted-vaccine were similar to those induced by other seasonal H1N1 strains and were superior to those induced by H5N1 vaccine strains. In mice previously primed with TIV, the unadjuvanted pandemic (H1N1) 2009 vaccine induced higher functional antibody titers than in naïve mice. However the AF03-adjuvanted vaccine induced similar antibody titers in both naïve and primed mice. The concomitant administration of TIV together with pandemic (H1N1) 2009 vaccine did not affect antibody responses generated against A/California/07/2009 or A/Brisbane/59/2007 seasonal H1N1 strain.The pandemic (H1N1) 2009 unadjuvanted influenza vaccine was shown to be immunogenic in mice after a single immunization. Formulation of the vaccine with AF03 adjuvant strongly increased its immunogenicity and enabledimmune response to the pandemic (H1N1) 2009 or to the H1N1 strain contained in the seasonal TIV.