Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect.

Publication Type
Journal Article
Year of Publication
Ledgerwood, Julie E; Zephir, Kathryn; Hu, Zonghui; Wei, Chih-Jen; Chang, Leejah; Enama, Mary E; Hendel, Cynthia S; Sitar, Sandra; Bailer, Robert T; Koup, Richard A; Mascola, John R; Nabel, Gary J; Graham, Barney S; VRC 310 Study Team
J Infect Dis
Date Published
2013 Aug 01
Adolescent; Adult; Antibodies, Viral; Female; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus; Humans; Immunization, Secondary; Influenza Vaccines; Male; Middle Aged; Time Factors; Vaccines, DNA; Vaccines, Inactivated; Young Adult

BACKGROUND: H5 DNA priming was previously shown to improve the antibody response to influenza A(H5N1) monovalent inactivated vaccine (MIV) among individuals for whom there was a 24-week interval between prime and boost receipt. This study defines the shortest prime-boost interval associated with an improved response to MIV.

METHODS: We administered H5 DNA followed by MIV at intervals of 4, 8, 12, 16, or 24 weeks and compared responses to that of 2 doses of MIV (prime-boost interval, 24 weeks).

RESULTS: H5 DNA priming with an MIV boost ≥12 weeks later showed an improved response, with a positive hemagglutination inhibition (HAI) titer in 91% of recipients (geometric mean titer [GMT], 141-206), compared with 55%-70% of recipients with an H5 DNA and MIV prime-boost interval of ≤8 weeks (GMT, 51-70) and 44% with an MIV-MIV prime-boost interval of 24 weeks (GMT, 27).

CONCLUSION: H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12-24 weeks. Clinical Trials Registration. NCT01086657.