A live attenuated influenza A(H5N1) vaccine induces long-term immunity in the absence of a primary antibody response

Kawsar R. Talaat, Catherine J. Luke, Surender Khurana, Jody Manischewitz, Lisa R. King, Bridget A. McMahon, Ruth A. Karron, Kristen D.C. Lewis, Jing Qin, Dean A. Follmann, Hana Golding, Kathleen M. Neuzil, Kanta Subbarao

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Highly pathogenic avian influenza A(H5N1) causes severe infections in humans. We generated 2 influenza A(H5N1) live attenuated influenza vaccines for pandemic use (pLAIVs), but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long-lasting immunity that could be detected by administration of inactivated subvirion influenza A(H5N1) vaccine (ISIV). Methods. The following groups were invited to participate in the study: persons who previously received influenza A(H5N1) pLAIV; persons who previously received an irrelevant influenza A(H7N3) pLAIV; and community members who were naive to influenza A(H5N1) and LAIV. LAIV-experienced subjects received a single 45-μg dose of influenza A(H5N1) ISIV. Influenza A(H5N1)- and LAIV-naive subjects received either 1 or 2 doses of ISIV. Results. In subjects who had previously received antigenically matched influenza A(H5N1) pLAIV followed by 1 dose of ISIV compared with those who were naive to influenza A(H5N1) and LAIV and received 2 doses of ISIV, we observed an increased frequency of antibody response (82% vs 50%, by the hemagglutination inhibition assay) and a significantly higher antibody titer (112 vs 76; P =. 04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in influenza A(H5N1) pLAIV-primed subjects. Conclusions. ISIV administration unmasked long-lasting immunity in influenza A(H5N1) pLAIV recipients, with a rapid, high-titer, high-quality antibody response that was broadly cross-reactive across several influenza A(H5N1) clades. Clinical Trials Registration. NCT01109329.

Original languageEnglish (US)
Pages (from-to)1860-1869
Number of pages10
JournalJournal of Infectious Diseases
Volume209
Issue number12
DOIs
StatePublished - Jun 15 2014

Keywords

  • H5N1
  • avian influenza
  • live attenuated
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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