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Trivalent inactivated influenza vaccine (TIV) contains 1 of 2 influenza B/lineages (B/Yamagata or B/Victoria) annually. We assessed prime-boost responses in young children following a change in the B/lineage included in TIV.Participants were primed during a clinical trial as infants or toddlers with two 0.25 or two 0.5 mL doses of 2008–2009 TIV containing B/Florida/4/06(Yamagata) antigen. In subsequent years, sequential subsets received annual age-appropriate doses of 2009–2010 and 2010–2011 TIV containing the changed influenza B/lineage antigen (B/Brisbane/60/08(Victoria)). Serologic response was assessed pre- and postimmunization by hemagglutination inhibition (HI; with/without ether treatment of influenza B antigen) and microneutralization. The primary immunogenicity outcome was the seroprotection rate (SPR) measured by HI without ether treatment (SPR:HI titers ≥40).Fifty-six children were included in 2009–2010 and 36 in 2010–2011 analyses. Before the 2009–2010 TIV dose, antibody to all 2008–2009 TIV components had fallen to low levels: SPR <10% for B/Florida/4/06(Yamagata) and B/Brisbane/60/08(Victoria) antigens. A single 2009–2010 TIV dose boosted antibody to the shared 2008–2009/2009–2010 influenza A antigens and to the priming 2008–2009 B/Florida/4/06(Yamagata) antigen with SPRs >85%. In contrast, antibody to the B/Brisbane/60/08(Victoria) antigen included in the 2009–2010 TIV remained low: SPR <25%. Antibody to the B/Brisbane/60/08(Victoria) antigen was not improved from a further dose in the 2010–2011 TIV: SPR 31% versus SPR 69% to B/Yamagata. A similar pattern of B/Yamagata dominance was observed when HI testing was conducted with antigen prepared by ether treatment.Repeated annual TIV doses containing B/Victoria-lineage antigen strongly recalled antibodies to the B/Yamagata antigen of first exposure, but elicited lower B/Victoria responses.