A live attenuated influenza A (H5N1) vaccine induces long-term immunity in the absence of a primary antibody response
KR Talaat, CJ Luke, S Khurana… - The Journal of …, 2014 - academic.oup.com
KR Talaat, CJ Luke, S Khurana, J Manischewitz, LR King, BA McMahon, RA Karron…
The Journal of infectious diseases, 2014•academic.oup.comBackground. 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 …
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 …
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.
Oxford University Press