Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect
Julie E Ledgerwood, Kathryn Zephir, Zonghui Hu, Chih-Jen Wei, Leejah Chang, Mary E Enama, Cynthia S Hendel, Sandra Sitar, Robert T Bailer, Richard A Koup, John R Mascola, Gary J Nabel, Barney S Graham, VRC 310 Study Team, Sarah Hubka, LaSonji Holman, Ingelise Gordon, Laura Novik, Pamela Costner, Floreliz Mendoza, Jamie Saunders, Brenda Larkin, Diane Johnson, Nina Berkowitz, Brandon Wilson, Tanya Clarke, Olga Vasilenko, Yesenia Merino, Joseph Casazza, Sheryl Young, Uzma Sarwar, Nicole L Luongo Susan Leitman, Charla Andrews, Phillip Gomez, Becky Sheets, Judy Stein, Galina Yamshchikov, Hope Decederfelt, Judith Starling, LaChonne Stanford, Rhonda Washington-Lewis, Kathy Rhone, Hanne Andersen, Meghan Kunchai, Ly Diep, Phyllis Zaia, Julie E Ledgerwood, Kathryn Zephir, Zonghui Hu, Chih-Jen Wei, Leejah Chang, Mary E Enama, Cynthia S Hendel, Sandra Sitar, Robert T Bailer, Richard A Koup, John R Mascola, Gary J Nabel, Barney S Graham, VRC 310 Study Team, Sarah Hubka, LaSonji Holman, Ingelise Gordon, Laura Novik, Pamela Costner, Floreliz Mendoza, Jamie Saunders, Brenda Larkin, Diane Johnson, Nina Berkowitz, Brandon Wilson, Tanya Clarke, Olga Vasilenko, Yesenia Merino, Joseph Casazza, Sheryl Young, Uzma Sarwar, Nicole L Luongo Susan Leitman, Charla Andrews, Phillip Gomez, Becky Sheets, Judy Stein, Galina Yamshchikov, Hope Decederfelt, Judith Starling, LaChonne Stanford, Rhonda Washington-Lewis, Kathy Rhone, Hanne Andersen, Meghan Kunchai, Ly Diep, Phyllis Zaia
Abstract
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.
Keywords: Avian influenza; DNA vaccine; H5N1; boost interval; hemagglutination inhibition.
Figures
Source: PubMed