Quadrivalent Inactivated Influenza Vaccine Non-inferior to Fluzone
SAN DIEGO, CA—A quadrivalent inactivated influenza vaccine (QIV) developed to reduce mismatch in predicting which B-lineage strains to include in annual trivalent influenza vaccines (TIV) has a similar safety and immunogenicity profile among children, adults, and seniors when compared with Fluzone, the currently licensed vaccine, according to results of three clinical trials reported at IDWeek 2012.
Of circulating influenza strains, approximately 20–25% are influenza B. Two distinct influenza B virus lineages, Victoria and Yamagata, have co-circulated in the United States for more than a decade, making predicting which one to include in TIVs difficult. In six of the past 12 influenza seasons, the B strain selected by health authorities for inclusion in the vaccine was not the predominant B-lineage strain that circulated during the next influenza season. Incorporating a strain from each B lineage, QIV seeks to reduce these mismatches.
Three Phase 2/3 trials were conducted in which children 6 months–<9 years of age (n=4,347), adults 18+ years (n=570), and seniors 65+ years (n=675) were randomly assigned to receive QIV (A/H1N1, A/H3N2, B/Victoria, and B/Yamagata), licensed TIV (Fluzone [Sanofi Pasteur]; both A strains and B/Victoria), or an alternate B-lineage TIV (AltB TIV; both A strains and B/Yamagata). Across the three studies, 3,307 subjects received QIV, 1,149 licensed TIV, and 1,136 AltB TIV.
Pain/tenderness at the injection site, irritability (children aged 6 to <24 months), myalgia, and malaise were the most common reactions and most were Grade 1 or 2 in severity.
Using predefined statistical criteria and as assessed by geometric mean HI titer ratios and seroconversion rates (four-fold rise in HI titer pre-vaccination to post-vaccination), antibody responses to all four QIV strains were non-inferior to each control TIV in each study, with the exception of seroconversion rates to A/H1N1 in seniors.
Similarly, geometric mean H1 titer ratios and seroconversion rates to both B strains in QIV were superior to each control TIV not containing the respective B strain, with the exception of geometric mean HI titer ratio to B/Victoria in seniors.
“QIV induced superior antibody responses to the B strain not represented in the TIV. QIV has the potential to be a useful alternative to TIV and offers the possibility of protection against both B lineages simultaneously,” reported David P. Greenberg, MD, from Sanofi Pasteur, Swiftwater, PA.
Sanofi Pasteur announced the filing a Supplemental Biologics License Application (sBLA) with the FDA for licensure of Fluzone QIV for active immunization of children and adults ≥6 months of age on October 18, 2012; the sBLA file has been accepted for full review.