Almond N, Jenkins A, Jones S, Arnold C, Silvera P, Kent K, Mills K H G, Stott E J
Division of Retrovirology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3QG, UK1.
J Gen Virol. 1999 Sep;80 ( Pt 9):2375-2382. doi: 10.1099/0022-1317-80-9-2375.
The presence or evolution of immune escape variants has been proposed to account for the failure of recombinant envelope vaccines to protect macaques against challenge with simian immunodeficiency virus (SIVmac). To address this issue, two groups of three cynomolgus macaques were immunized with recombinant SIV Env vaccines using two different vaccine schedules. One group of macaques received four injections of recombinant SIV gp120 in SAF-1 containing threonyl muramyl dipeptide as adjuvant. A second group were primed twice with recombinant vaccinia virus expressing SIV gp160 and then boosted twice with recombinant SIV gp120. Both vaccine schedules elicited neutralizing antibodies to Env. However, on the day of challenge, titres of anti-Env antibodies measured by ELISA were higher in macaques primed with recombinant vaccinia virus. Following intravenous challenge with 10 monkey infectious doses of the SIVmac J5M challenge stock, five of the six immunized macaques and all four naive controls became infected. The virus burdens in PBMC of macaques that were primed with recombinant vaccinia virus were lower than those of naive controls, as determined by virus titration and quantitative DNA PCR. Sequence analysis was performed on SIV env amplified from the blood of immunized and naive infected macaques. No variation of SIV env sequence was observed, even in macaques with a reduced virus load, suggesting that the appearance of immune escape variants does not account for the incomplete protection observed. In addition, this study indicates that the measurement of serum neutralizing antibodies may not provide a useful correlate for protection elicited by recombinant envelope vaccines.
有人提出免疫逃逸变异株的存在或演变可解释重组包膜疫苗无法保护猕猴免受猿猴免疫缺陷病毒（SIVmac）攻击的原因。为解决这一问题，两组各三只食蟹猴按照两种不同的疫苗接种方案用重组SIV包膜疫苗进行免疫。一组食蟹猴接受四次含有苏氨酰胞壁酰二肽作为佐剂的SAF-1中的重组SIV gp120注射。第二组先用表达SIV gp160的重组痘苗病毒进行两次初免，然后用重组SIV gp120进行两次加强免疫。两种疫苗接种方案均诱导产生了针对Env的中和抗体。然而，在攻击当天，通过ELISA检测的抗Env抗体滴度在以重组痘苗病毒初免的猕猴中更高。在用10个猴感染剂量的SIVmac J5M攻击毒株进行静脉攻击后，六只免疫猕猴中的五只和所有四只未免疫对照均被感染。通过病毒滴定和定量DNA PCR测定，以重组痘苗病毒初免的猕猴外周血单核细胞中的病毒载量低于未免疫对照。对从免疫和未免疫感染猕猴血液中扩增的SIV env进行了序列分析。即使在病毒载量降低的猕猴中也未观察到SIV env序列的变异，这表明免疫逃逸变异株的出现并不能解释所观察到的不完全保护现象。此外，本研究表明血清中和抗体的测定可能无法为重组包膜疫苗诱导的保护提供有用的相关性指标。
