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Characterization of simian and human immunodeficiency chimeric viruses re-isolated from vaccinated macaque monkeys
1Laboratory of Viral Pathogenesis, Research Center for AIDS, Institute for Virus Research, Kyoto University, Japan.
Abstract:
Monkeys that have been vaccinated with nef-deleted SHIVs were either fully or partially protected against challenge with acute pathogenic SHIV-89.6 P. Viruses isolated from these vaccinated monkeys were all found to be the 89.6 P challenge virus using PCR amplification and restriction enzyme analysis of the env region of the viruses. Analysis of the 3'-end of the env region and 5'-half of the nef region using a heteroduplex mobility assay revealed that the parental 89.6 P and re-isolated viruses from unvaccinated 89.6 P-infected monkeys had quite an abundant and similar heterogeneous quasispecies population. In contrast, the viruses isolated from the vaccinated monkeys had different and fewer quasispecies indicating a selective immune pressure in the vaccinated monkeys. The in vitro replication of the viruses isolated from the vaccinated monkeys in human and macaque peripheral blood mononucular cells (PBMCs) as well as in established cell lines such as M8166 and HSC-F cells, were slow and delayed when compared to the parental 89.6 P and re-isolated viruses from unvaccinated 89.6 P-infected monkeys. Further comparison revealed that in HSC-F cells the viruses from vaccinated monkeys again showed delayed and weak CD4(+) cell down-modulation as well as having little or no effect on cell growth or cell viability on HSC-F cells and monkey PBMC. Thus we noticed that these re-isolated 89.6 P viruses from the vaccinated monkeys had changed or had been selected for low pathogenic viruses in the monkeys. This suggests that though the vaccination did not completely prevent the replication of the challenge virus in the monkeys it did contain the challenge virus by suppressing the pathogenic variants. This further enhances the prospects of this nef-deleted SHIV as the bases for effective anti-HIV vaccine candidates.
Insights
Vaccinating monkeys with nef-deleted simian-human immunodeficiency viruses (SHIVs) offered protection against pathogenic SHIV challenge. The study found that re-isolated viruses from vaccinated monkeys showed reduced pathogenicity, suggesting potential for effective anti-HIV vaccines.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- Developing effective vaccines against human immunodeficiency virus (HIV) remains a critical global health challenge.
- Simian-human immunodeficiency viruses (SHIVs) are valuable tools for studying HIV pathogenesis and vaccine efficacy.
- The role of the nef gene in SHIV pathogenicity and its potential as a vaccine target require further investigation.
Purpose of the Study:
- To evaluate the protective efficacy of nef-deleted SHIVs in a primate model.
- To characterize the viral variants that emerge after challenge in vaccinated and unvaccinated animals.
- To assess the pathogenicity and replication capacity of re-isolated viruses.
Main Methods:
- Monkeys were vaccinated with nef-deleted SHIVs and subsequently challenged with pathogenic SHIV-89.6P.
- Viruses from vaccinated and unvaccinated monkeys were isolated and analyzed using PCR, restriction enzyme analysis, and heteroduplex mobility assays.
- In vitro replication kinetics and cellular effects (CD4+ cell down-modulation, cell viability) of re-isolated viruses were assessed in various cell types.
Main Results:
- Vaccinated monkeys showed partial or full protection against SHIV-89.6P challenge.
- Viruses re-isolated from vaccinated monkeys exhibited reduced quasispecies diversity and slower replication in vitro compared to parental virus.
- Re-isolated viruses from vaccinated monkeys displayed attenuated pathogenicity, including delayed CD4+ cell down-modulation and minimal impact on cell growth.
Conclusions:
- Vaccination with nef-deleted SHIVs effectively suppressed pathogenic viral variants, leading to attenuated viral strains.
- The study demonstrates that nef-deleted SHIVs can contain viral replication and reduce pathogenicity, though not completely prevent infection.
- These findings support the development of nef-deleted SHIVs as promising candidates for effective anti-HIV vaccine development.
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