IMMUNOGENICITY OF RECOMBINANT VACCINIA VIRUS EXPRESSING ENV GLYCOPROTEINS

我们以前报道过用重组SIVmne免疫， 包膜（gp160）疫苗保护猕猴免受静脉注射 用克隆的同源病毒E11S攻击。 本研究 证实了这一观察结果，并发现疫苗是有效的， 不仅可以对抗在人类T细胞系上生长的病毒， 在猕猴PBMC上生长的病毒。 然而，保护的广度是 有限公司 在三个实验中，3/10的动物用 亲本未克隆的SIVmne被完全保护。 剩余 动物中，3只为一过性病毒阳性，4只为 攻毒后持续阳性，10例未免疫 对照动物。 保护作用与 抗同源SIVmne的血清中和抗体或 SIVmac251病毒 为了更深入地了解 机制，我们分析了在包膜区的核苷酸序列， 未克隆的攻击病毒，并将它们与 受感染动物的PBMC。 大多数（85%）未克隆的 攻击病毒与产生攻击病毒的分子克隆同源， 制备疫苗（E11S型）。 剩下的15%， V1区的变化（变体类型）。 感染的对照动物 这种未克隆的病毒具有两种基因型的不同比例， 而3/4免疫但持续感染的动物具有> 99%的 感染后早期的变异类型。 这些结果表明 由重组gp160疫苗引发的保护性免疫， 主要限于同源病毒，并建议 针对V1区的免疫反应可能是 包膜蛋白可能起保护作用。 的结果 研究报告于1999年初发表。 资助NIH拨款RR00166。 Polacino，P.，Stallard，J. E.克拉尼茨基，D. C. Montefiori，A. J. Langlois，B. a. Richardson，J. Overbaugh，W. R.莫顿河e. Benveniste和S. L.胡1999. 保护的宽度有限 猴免疫缺陷病毒SIVmne gp160诱导免疫 联合免疫方案中的疫苗。 J. Virol. 73：618 - 630。

We previously reported that immunization with recombinant SIVmne envelope (gp160) vaccines protected macaques against an intravenous challenge by the cloned homologous virus, E11S. In this study, we confirmed this observation and found that the vaccines were effective not only against virus grown on human T-cell lines, but also against virus grown on macaque PBMC. The breadth of protection, however, was limited. In three experiments, 3/10 animals challenged with the parental uncloned SIVmne were completely protected. Of the remaining animals, three were transiently virus-positive and four were persistently positive after challenge, as were 10 non-immunized control animals. Protection was not correlated with levels of serum-neutralizing antibodies against the homologous SIVmne or a related virus, SIVmac251. To gain further insight into the protective mechanism, we analyzed nucleotide sequences in the envelope region of the uncloned challenge virus and compared them w ith those present in the PBMC of infected animals. The majority (85%) of the uncloned challenge virus was homologous to the molecular clone from which the vaccines were made (E11S type). The remaining 15% contained conserved changes in the V1 region (variant types). Control animals infected with this uncloned virus had varying proportions of both genotypes, whereas 3/4 immunized but persistently infected animals had >99% of the variant types early after infection. These results indicate that the protective immunity elicited by recombinant gp160 vaccines is restricted primarily to the homologous virus and suggest the possibility that immune responses directed to the V1 region of the envelope protein may play a role in protection. The results of this study were published in early 1999. FUNDING NIH grant RR00166. Polacino, P., V. Stallard, J. E. Klaniecki, D. C. Montefiori, A. J. Langlois, B. A. Richardson, J. Overbaugh, W. R. Morton, R. E. Benveniste, and S. L. Hu. 1999. Limited breadth of the protective immunity elicited by simian immunodeficiency virus SIVmne gp160 vaccines in a combination immunization regimen. J. Virol. 73:618-630.