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SIVmac vaccine studies using whole inactivated virus antigen sequentially depleted of viral proteins
Abstract:
Groups of four rhesus monkeys were immunised at 0, 1, 2, and 13 months with whole inactivated SIVmac32H, SIVmac depleted of the outer envelope glycoprotein gp130, virus cores depleted of the lipid membrane (and hence transmembrane glycoproteins), or purified gag protein. These macaques plus controls were challenged with either the homologous SIVmac251-32H grown in human cells or the same virus passed once through monkey cells. None of those challenged with monkey-grown virus were protected, whereas all in the whole and gp130-depleted virus groups, and one in the core group resisted challenge with human-grown virus. As the only difference between the challenge viruses was a single in vitro passage in monkey cells it can be concluded that protection was solely due to human cell components. Finally, passive transfer of high titer IgG from monkeys infected with the homologous challenge virus failed to protect monkeys from infection despite the presence of circulating neutralising antibodies.
Insights
Vaccine protection against simian immunodeficiency virus (SIV) depended on human cell components. Even with neutralizing antibodies, passive antibody transfer failed to protect monkeys from infection.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- Developing effective vaccines against simian immunodeficiency virus (SIV) is crucial for understanding and combating human immunodeficiency virus (HIV).
- Previous studies have explored various vaccine candidates, including inactivated whole virus, viral components, and virus-like particles.
Purpose of the Study:
- To investigate the protective efficacy of different SIVmac32H vaccine preparations against homologous SIV challenge.
- To determine the role of human cell-derived components in vaccine-induced protection.
- To assess the effectiveness of passive antibody transfer in preventing SIV infection.
Main Methods:
- Rhesus monkeys were immunized with whole inactivated SIVmac32H, gp130-depleted SIVmac, virus cores, or purified gag protein.
- Immunized and control macaques were challenged with homologous SIVmac251-32H grown in human cells or monkey cells.
- Passive transfer of high-titer IgG from infected monkeys was performed.
Main Results:
- No protection was observed in monkeys challenged with monkey cell-passaged SIV.
- Complete protection against human cell-grown SIV was achieved with whole inactivated virus and gp130-depleted virus vaccines.
- Partial protection was observed in the virus core vaccine group.
- Passive transfer of antibodies did not prevent SIV infection despite detectable neutralizing antibodies.
Conclusions:
- Vaccine-induced protection against SIVmac challenge is dependent on human cell-derived components present in the vaccine.
- The cellular origin of the challenge virus significantly impacts vaccine efficacy.
- Neutralizing antibodies alone, transferred passively, are insufficient to confer protection against SIV infection in this model.