A Live Attenuated Influenza A(H5N1) Vaccine Induces Long-Term Immunity in the Absence of a Primary Antibody Response

• Published in: The Journal of infectious diseases Vol. 209; no. 12; pp. 1860 - 1869
• Main Authors: Talaat, Kawsar R., Luke, Catherine J., Khurana, Surender, Manischewitz, Jody, King, Lisa R., McMahon, Bridget A., Karron, Ruth A., Lewis, Kristen D. C., Qin, Jing, Follmann, Dean A., Golding, Hana, Neuzil, Kathleen M., Subbarao, Kanta
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.06.2014
• Series: Editor's choice
• Subjects: Adult; Antibodies; Antibodies, Viral - blood; Antibody Affinity; Antibody Formation - immunology; Antibody response; Applied microbiology; Attenuated vaccines; Biological and medical sciences; Cross Reactions; Dosage; Female; Fundamental and applied biological sciences. Psychology; H5N1 subtype influenza A virus; Healthy Volunteers; Hemagglutination Inhibition Tests; Humans; Inactivated vaccines; Infectious diseases; Influenza A virus; Influenza A Virus, H5N1 Subtype - immunology; Influenza A Virus, H7N3 Subtype - immunology; Influenza vaccines; Influenza Vaccines - immunology; Influenza Vaccines - therapeutic use; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Pandemics; Transcriptional regulatory elements; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - immunology; Vaccines, Attenuated - therapeutic use; Virology; VIRUSES; Young Adult; Virus; Infection; Influenzavirus A; Immune response; Influenza A virus; Viral disease; Orthomyxoviridae; Influenza A; Vaccine; Attenuated strain; Humoral immunity; live attenuated; H5N1; vaccine; avian influenza
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiu123

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-ug 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-dade 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.