Limited breadth of the protective immunity elicited by simian immunodeficiency virus SIVmne gp160 vaccines in a combination immunization regimen

We previously reported that immunization with recombinant simian immunodefi ciency virus 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 n ot only against virus grown on human T-cell lines but also against virus gr own on macaque peripheral blood mononuclear cells (PBMC). The breadth of pr otection, however, was limited. In three experiments, 3 of 10 animals chall enged with the parental uncloned SIVmne were completely protected. Of the r emaining animals, three were transiently virus positive and four were persi stently positive after challenge, as were 10 nonimmunized control animals. Protection was not correlated with levels of serum-neutralizing antibodies against the homologous SIVmne or a related virus, SIVmac251. To gain furthe r insight into the protective mechanism, we analyzed nucleotide sequences i n the envelope region of the uncloned challenge virus and compared them wit h those present in the PBMC of infected animals. The majority (85%) of the uncloned challenge virus was homologous to the molecular clone from which t he vaccines were made (E11S type). The remaining 15% contained conserved ch anges in the V1 region (variant types). Control animals infected with this uncloned virus had different proportions of the two genotypes, whereas thre e of four immunized but persistently infected animals had > 99% of the vari ant 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 dir ected to the V1 region of the envelope protein play a role in protection.