High dose (HD-IIV), standard dose (SD-IIV), and MF-59 adjuvanted (aIIV) influenza vaccines are licensed for adults ≥65 years old, but there is no preferential recommendation for a specific product. These vaccines are manufactured using egg-adapted high growth reassortant viruses. Recent data suggests that antibodies generated by egg-adapted A(H3N2) viruses may contribute to reduced vaccine effectiveness. We report results from the first year of a two year randomized trial of vaccine immunogenicity, including response to A(H3N2) vaccine strains propagated in egg (H3N2-egg) and cell culture (H3N2-cell).
Adults 65-74 years old were randomized to receive 2016-17 trivalent inactivated influenza vaccines: SD-IIV (n=60), HD-IIV (n=59), and aIIV (n=60). Pre- and post-vaccination sera were analyzed by microneutralization assays (MN) to egg- and cell-propagated A(H3N2) vaccine virus, A/Hong Kong/4801/2014 and tested by hemagglutination inhibition (HI) assays to A/California/7/2009 A(H1N1)pdm09-like and B/Brisbane/60/2008-like viruses. Endpoints were post-vaccination geometric mean titer (GMT), mean fold rise (MFR), and seroconversion. Respiratory swabs from adults with acute respiratory illness during the season were tested by RT-PCR to identify vaccine failures.
Pre-vaccination MN and HI titers were similar across study arms. There were no differences across study arms in postvaccination MN GMT, seroconversion, and MFR against H3N2-egg and H3N2-cell (figure). However, response was lower against H3N2-cell than H3N2-egg. HI MFR for H1N1pdm09 and B/Brisbane were significantly higher in HD-IIV than SD-IIV and aIIV recipients (figure). Eight participants had PCR-confirmed A(H3N2) infection: 1/60 (2%) SD-IIV, 4/57 (7%) HD-IIV, and 3/60 (5%) aIIV recipients. Postvaccination H3N2-cell MN GMT was 15 and 63, respectively for A(H3N2) cases and noncases. Among the eight A(H3N2) cases, post-vaccination MN titers were ≥1:40 against H3N2-egg for 6 cases versus 0 cases against H3N2-cell.
Post-vaccination MN titers against H3N2 egg- and cell-propagated vaccine viruses were similar across study arms, though antibody response was lower to H3N2-cell. HD-IIV generated greater antibody response against A(H1N1)pdm09 and B compared with SD-IIV or aIIV.
J. King, None
S. Spencer, None
B. Flannery, None
E. Belongia, None