Naval Medical Research Center Detachment, Lima, Peru.
Vaccine. 2011 Mar 24;29(15):2691-6. doi: 10.1016/j.vaccine.2011.01.077. Epub 2011 Feb 17.
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 × 10(4)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.
补骨脂素是一种光反应性化合物,在暴露于 UVA 辐射后会与嘧啶碱基交联。在本实验中,我们测试了一种补骨脂素灭活的登革热候选疫苗在非人类灵长类动物中的保护效果。两组 7 只南迪长尾猴(Aotus nancymaae)分别接受 10ng 剂量的灭活 DENV1 加铝佐剂或单独的铝佐剂(对照组)。剂量于第 0、14 和 28 天皮内注射。然后,猴子在第 132 天接受 1.1×10(4)PFUs 的西太平洋 74 型 DENV-1 挑战接种。在 62 天,只有 1/7 接种疫苗的猴子可检测到 IgM,但 7/7 的猴子仍可检测到 IgG 和中和抗体。对照组猴子均未检测到 IgM、IgG 或中和抗体。在 3/7 只接种疫苗的猴子和 5/6 只对照猴子(因怀孕而去除 1 只)中检测到 DENV-1 病毒血症(p=0.27),但与对照组动物相比,接种疫苗猴子的病毒血症天数从 3.67 天/动物减少到 0.71 天/动物(p=0.051)。补骨脂素灭活的 DENV1 在南迪长尾猴中具有免疫原性,在实验性挑战后病毒血症天数有减少的趋势。