Prime-Boost Interval Matters: A Randomized Phase 1 Study to Identify the Minimum Interval Necessary to Observe the H5 DNA Influenza Vaccine Priming Effect

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.

Avian influenza, DNA vaccine, H5N1, boost interval, hemagglutination inhibition