Host immune response against an attenuated vaccine virus with deglycosylation in env.
Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10390)
Mori KM, Sugimoto CS, Shioda TS, Yasutomi YY, Yamamoto NY, Nagai YN AIDS Research Center, National Institute of Infectious Diseases, Tsukuba, Japan
A mutant with 5 deglycosylations in gp120 (d-5G) replicated robustly in rhesus macaques similar to a parental SIVmac239 in primary infection, but was tightly contained after 8 weeks postinfection (wpi). To explore the mechanism of the containment of the infection, host immune response in 5 rhesus macaques were studied. Heavy glycan shield in vial spikes in HIV/SIV confers neutralization resistance in clinical HIV-1 isolates and SIVmac239. Consistently, 3 of 5 animals induced neutralizing antibody (NAb) against d-5G after acute plasma viremia. However, 2 animals induced very low or undetectable NAb. Cellular immune response such as CTL plays an important role for clearing infected cells in acute viral replication. We examined viral specific CD8+T cells and CD4+T cells by IFN-γ ELISPOT. Viral specific CD8+ T cells were induced in 3 animals and but not in 2 animals during 8 wpi. Viral specific CD4+ T cells were induced in the same animals and more rapidly compared to viral specific CD8+ T cell response. Thus, viral specific immune responses were diverse among the animals. Interestingly NAb titer and cellular response were negatively correlated in all animals. These results indicated the undefined mechanism that polarized immune response toward Th1 or Nab induction but not Th2 during the primary infection, since high Env binding Ab titer was detected in all animals. Thus, the deglycosylation mutation in SIV allowed the host to control otherwise the lethal infection. But we could not find any evidence of the association between the antigenic alteration by deglycosylation in SIV and the specific immune response.
Keywords: AEGIS, Vaccines, Attenuated, SIV, Genes, env, Macaca mulatta, CD8-Positive T-Lymphocytes, HIV Envelope Protein gp120, Virus Replication, Viremia, Animal, genetics, immunology, virology
