Prime-Boost Interval Matters: A Randomized Phase 1 Study to Identify the Minimum Interval Necessary to Observe the H5 DNA Influenza Vaccine Priming Effect
Year of Publication
Ledgerwood, JE; Zephir, K; Hu, Z; Wei, CJ; Chang, L; Enama, ME; Hendel, CS; Sitar, S; Bailer, RT; Koup, RA; Mascola, JR; Nabel, GJ; Graham, BS; The VRC 310 Study Team
J Infect Dis
Antibodies; Avian influenza; boost interval; DNA; H5n1; hemagglutination inhibition; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins; immunization; Influenza Vaccines; Influenza Virus/genetics/immunology; Vaccines Inactivated; Viral/blood
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.