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Influenza B/Victoria Antigen Induces Strong Recall of B/Yamagata But Lower B/Victoria Response in Children Primed With Two Doses of B/Yamagata

Skowronski, Danuta M. MD, FRCPC*†; Hottes, Travis S. MSc*; De Serres, Gaston MD, PhD; Ward, Brian J. MDCM§; Janjua, Naveed Z. MD, MSc, DrPH*†; Sabaiduc, Suzana BSc*; Chan, Tracy BSc, RMCCM*; Petric, Martin PhD, FCCM*

The Pediatric Infectious Disease Journal: October 2011 - Volume 30 - Issue 10 - p 833-839
doi: 10.1097/INF.0b013e31822db4dc
Original Studies

Objectives: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

From the *British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada; †School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada; ‡Institut national de santé publique du Québec, Québec, Québec, Canada; and §McGill University Health Centre (MUHC) Vaccine Research Unit, Montreal General Hospital, Montréal, Québec, Canada.

Accepted for publication April 19, 2011.

Supported by funds from Canadian Institutes of Health Research (ID#: CVC-99971) as well as the Ministère de la santé et des services sociaux du Québec. Within 36 months of submission, D.M.S. was Principal Investigator on the TITRE I trial for which influenza vaccine was provided free by Sanofi Pasteur; G.D.S. received research grants from Glaxo Smith Kline and Sanofi Pasteur for unrelated studies; and B.J.W. shared a CIHR team grant with GlaxoSmithKline investigators.

The authors have no other funding or conflicts of interest to disclose.

Presented, in part, at 14th Annual Conference on Vaccine Research, May 16–18, 2011, Baltimore, abstract 124.

Clinical trial registration: NCT00710866 (TITRE I); NCT01067404 (TITRE II); NCT01235000 (TITRE IIB).

Address for correspondence: Danuta M. Skowronski, MD, British Columbia Centre for Disease Control, 655 West 12th Ave., Vancouver, British Columbia, Canada. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.