Analysis of the vaccine-induced influenza B virus hemagglutinin-specific antibody dependent cellular cytotoxicity response

Influenza A virus (IAV) and influenza B virus (IBV) cause substantial morbidity and mortality during seasonal epidemics. On basis of variation in the surface glycoprotein hemagglutinin, two antigenically distinct lineages of IBV are distinguished: B/Victoria/2/87-like (B/Vic) and B/Yamagata/16/88-like (B/Yam). To prevent IAV and IBV infections, both trivalent (containing IBV of one lineage) and quadrivalent (containing IBV of both lineages) influenza vaccines are used. In addition to virus-neutralizing antibodies, inactivated influenza vaccines induce antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC). Here, we determine whether vaccination with trivalent or quadrivalent inactivated influenza vaccine induces ADCC mediating antibodies directed to IBV of the two different lineages, and whether these antibodies cross-react with IBV of the opposing lineage. A robust ADCC assay based on the use of recombinant hemagglutinin and a continuous natural killer cell line that expresses FcγRIII (CD16) was used to detect the presence of ADCC mediating antibodies. Paired pre- and post-vaccination serum samples from 26 and 15 study subjects that received a trivalent or quadrivalent inactivated influenza vaccine, respectively, were assessed for the presence of ADCC mediating antibodies specific for HA derived from viruses of the B/Vic or B/Yam-lineage. Furthermore, the relative contribution of HA1- and HA2-subunit-specific antibodies to the ADCC response was determined. We found that seasonal inactivated influenza vaccines induce HA-head- and HA-stalk-specific antibodies that mediate ADCC. As expected, the quadrivalent vaccine induced antibodies to HA from both IBV lineages. Notably, a trivalent vaccine containing HA from the B/Vic lineage induced antibodies that cross-react with the B/Yam lineage.

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