Desrosiers R C, Wyand M S, Kodama T, Ringler D J, Arthur L O, Sehgal P K, Letvin N L, King N W, Daniel M D
New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772.
Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353-7. doi: 10.1073/pnas.86.16.6353.
Rhesus monkeys were immunized by multiple inoculations with purified, disrupted, noninfectious simian immunodeficiency virus (SIV) in adjuvant. Immunized monkeys developed anti-SIV antibodies detectable by whole-virus ELISA and by immunoblot reactivity; these antibodies had weak neutralizing activity. One week after the last immunization, monkeys were challenged with 200-1000 animal infectious doses of uncloned, live SIV. The same strain of SIV that was used for vaccination was also used for challenge. Anamnestic antibody responses and SIV recovery from peripheral blood were used to evaluate infection following the live virus challenge; two of six vaccinated monkeys showed no evidence of infection following the live virus challenge. Transfusion of 10 ml of whole blood from these two into uninfected, naive rhesus monkeys did not result infection of the recipients, providing further support for the lack of infection in the two previously vaccinated animals. Four of four unvaccinated control monkeys inoculated with these doses of live SIV became infected and three of these died with AIDS 118-258 days after infection. Only one of the six vaccinated monkeys has died to date. In situ hybridization with lymph node biopsy specimens suggested that the virus load was much higher in control macaques than in vaccinated macaques. These results indicate that vaccination with inactivated whole virus can protect macaques against challenge with live SIV. Furthermore, they provide hope that vaccine protection against human AIDS virus infection may be possible.
恒河猴通过在佐剂中多次接种纯化的、经裂解的、无感染性的猿猴免疫缺陷病毒(SIV)进行免疫。免疫后的猴子产生了可通过全病毒酶联免疫吸附测定(ELISA)和免疫印迹反应检测到的抗SIV抗体;这些抗体具有较弱的中和活性。在最后一次免疫后一周,用200 - 1000个动物感染剂量的未克隆活SIV对猴子进行攻击。用于疫苗接种的SIV毒株也用于攻击。用记忆性抗体反应和从外周血中回收SIV来评估活病毒攻击后的感染情况;六只接种疫苗的猴子中有两只在活病毒攻击后未显示出感染迹象。将这两只猴子的10毫升全血输给未感染的、未经免疫的恒河猴,未导致受者感染,这进一步证明了之前接种过疫苗的两只动物未被感染。四只接种这些剂量活SIV的未接种疫苗的对照猴子被感染,其中三只在感染后118 - 258天死于艾滋病。到目前为止,六只接种疫苗的猴子中只有一只死亡。对淋巴结活检标本进行原位杂交表明,对照猕猴中的病毒载量远高于接种疫苗的猕猴。这些结果表明,用灭活全病毒进行疫苗接种可以保护猕猴免受活SIV的攻击。此外,它们为针对人类艾滋病病毒感染的疫苗保护提供了希望。