Immunogenicity and protective efficacy of a psoralen-inactivated dengue-1 virus vaccine candidate in Aotus nancymaae monkeys

Abstract: Psoralens are photoreactive compounds that cross-link pyrimidines after exposure to UVA radiation. In this experiment, we tested the protective efficacy of a psoralen-inactivated dengue vaccine candidate in non-human primates. Two groups of 7 Aotus nancymaae monkeys received either 10ng per dose of inactivated DENV1 plus alum adjuvant or alum alone (controls). Doses were injected intradermally on days 0, 14, and 28. Monkeys then received a challenge inoculation of 1.1×104 PFUs of WestPac 74 DENV-1 on day 132. At 62 days, only 1/7 vaccinated monkeys had detectable IgM, but IgG and neutralizing antibody remained detectable in 7/7. No IgM, IgG, or neutralizing antibody was detectable in control monkeys. DENV-1 viremia was detected after challenge in 3/7 vaccinated monkeys and 5/6 control monkeys (with one removed due to pregnancy) (p =0.27), but days of viremia were reduced from 3.67 days/animal among controls to 0.71 days/animal among vaccinated monkeys (p =0.051). Psoralen-inactivated DENV1 is immunogenic in Aotus nancymaae with a trend towards a reduction in days of viremia following experimental challenge. [Copyright &y& Elsevier]