Safety and Immunogenicity of a Subvirion Monovalent Unadjuvanted Inactivated Influenza A(H3N2) Variant Vaccine in Healthy Persons >= 18 Years Old

• Type of Material: Article
• Authors: Wendy A. Keitel, Baylor College of Medicine; Lisa A. Jackson, Group Health Research Institute; Srilatha Edupuganti, Emory University; Patricia L. Winokur, University of Iowa; Mark Mulligan, Emory University; Natalie Thornburg, Emory University; Shital M. Patel, Baylor College of Medicine; Nadine Rouphael, Emory University; Sandhya Bangaru, Vanderbilt University; Monica M. McNeal, University of Cincinnati; Abbie R. Bellamy, EMMES Corporation; Heather R. Hill, EMMES Corporation
• Language: English
• Date: 2015-08-15
• Publisher: OXFORD UNIV PRESS INC
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Author.
• Final Published Version (URL): http://dx.doi.org/10.1093/infdis/jiv056
• Title of Journal or Parent Work: Journal of Infectious Diseases
• Volume: 212
• Issue: 4
• Start Page: 552
• End Page: 561
• Grant/Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases (contracts HHSN272200800002C [to Baylor College of Medicine], HHSN272200800004C [to Group Health Research Institute], HHSN272200800005C [to Emory University School of Medicine], HHSN272200800008C [to the University of Iowa and Iowa VA Health System], HHSN272200800006C [to the University of Cincinnati], HHSN272200800007C [to Vanderbilt University], and HHSN272200800013C [to the EMMES Corporation]) and the National Center for Advancing Translational Sciences (award UL1TR000454), NIH; and the Georgia Research Alliance.
• Keywords: HUMANS; ANTIBODY; Life Sciences & Biomedicine; Science & Technology; IMMUNE-RESPONSE; immunization; H3N2 variant; MEMORY; immune responses; influenza; Immunology; Microbiology; Infectious Diseases; pandemic; EFFICACY; VIRUS

Abstract

Background. Variant influenza A(H3N2) viruses (H3N2v) have transmitted recently from pigs to humans in the United States. Vaccines strategies are needed. Methods. Healthy adults received 2 doses of subvirion H3N2v vaccine (15 μg of hemagglutinin/dose) 21 days apart in this open-label trial. Serum hemagglutination inhibition (HAI) and neutralizing (Neut) antibody (Ab) titers were measured before and 8 and 21 days after each dose. Memory B-cell (MBC) responses were assessed. Results. Vaccine was well tolerated. A total of 40% of subjects had an HAI Ab titer of ≥40 before vaccination. Eight-seven percent (95% confidence interval [CI], 79%-93%) and 73% (95% CI, 63%-81%) of subjects 18-64 years old (98 subjects) and ≥65 years old (90 subjects), respectively, had an HAI titer of ≥40 21 days after dose 1 (P =. 01); 51% (95% CI, 41%-61%) and 52% (95% CI, 41%-62%) of younger and older subjects, respectively, developed ≥4-fold rises in titer (P = not significant). Neut Ab response patterns were similar. Geometric mean titers were higher in younger subjects. Dose 2 provided no significant enhancement in responses. Cross-reactive MBCs were detected before vaccination and expanded after vaccination. Preexisting H3N2v-specific MBCs positively correlated with early increases in vaccine-induced Ab. Conclusions. In most healthy adults, one 15-μg dose of vaccine elicited levels of HAI Abs associated with protection. Studies in children and elderly individuals are indicated to define the immunization needs of these groups.