Homologous Boosting with Adenoviral Serotype 5 HIV Vaccine (rAd5) Vector Can Boost Antibody Responses Despite Preexisting Vector-Specific Immunity in a Randomized Phase I Clinical Trial
Year of Publication
Sarwar, UN; Novik, L; Enama, ME; Plummer, SA; Koup, RA; Nason, MC; Bailer, RT; McDermott, AB; Roederer, M; Mascola, JR; Ledgerwood, JE; Graham, BS; The VRC 015 Study Team
Adenoviridae; Adolescent; Adult; AIDS Vaccines; biosynthesis; Enzyme-Linked Immunosorbent Assay; Genetic Vectors; HIV Antibodies; immunology
BACKGROUND: Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine. METHODS: Thirty-one adults, 18-55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks. RESULTS: Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boost. CONCLUSIONS: Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.