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Vaccine protection and reduced virus load from heterologous macaque-propagated SIV challenge
J L Heeney1, L Holterman, P ten Haaft
1Laboratory of Viral Pathogenesis, Biomedical Primate Research Center TNO, Rijswijk, The Netherlands.
Abstract:
The efficacy of vaccine protection afforded by live attenuated vaccines was tested by heterologous SIVtno8980 challenge following successful protection against homologous SIVmac32H challenge. Animals immunized with the attenuated SIVmacBK28 molecular clone were asymptomatic and virus isolation negative by quantitative virus isolation prior to challenge. Two groups of four animals previously immunized 5 years and 4 months (respectively) were challenged with 100 MID50 of SIVtno8980, as was a third group of four naive controls. All control animals that were challenged developed high levels of plasma antigenemia within 2 weeks of challenge and developed rapid Th/m cell loss whereas vaccinated animals did not. Quantitative virus isolation from peripheral blood mononuclear cells revealed that one of four animals in each group became virus isolation positive but that the virus load in the two vaccinated animals was markedly lower than in nonvaccinated controls. Studies are underway to determine the duration and immunological correlates of protection from AIDS.
Insights
Live attenuated vaccines provided protection against simian-human immunodeficiency virus (SHIV) challenge. Vaccinated macaques showed no signs of disease and lower viral loads compared to unvaccinated controls, indicating vaccine efficacy.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Live attenuated vaccines are a promising strategy for preventing simian-human immunodeficiency virus (SHIV) infection.
- Previous studies demonstrated protection against homologous SHIV challenge with SIVmacBK28.
- The durability and breadth of protection remain critical questions.
Purpose of the Study:
- To evaluate the efficacy of live attenuated vaccines against heterologous SHIV challenge.
- To assess the duration of vaccine-induced protection.
- To investigate the immunological correlates of protection.
Main Methods:
- Animals previously immunized with SIVmacBK28 were challenged with a heterologous SIVtno8980 strain.
- A naive control group was included for comparison.
- Plasma antigenemia, Th/m cell counts, and quantitative virus isolation from peripheral blood mononuclear cells were monitored.
Main Results:
- Vaccinated animals remained asymptomatic and virus-isolation negative prior to challenge.
- Following heterologous challenge, control animals developed high antigenemia and rapid Th/m cell loss.
- Vaccinated animals showed no significant signs of disease, with one animal in each group becoming virus positive at a markedly lower viral load than controls.
Conclusions:
- Live attenuated vaccines confer significant protection against heterologous SHIV challenge.
- Protection appears durable, with efficacy observed 5 years post-immunization.
- Further studies are needed to define the duration and immunological basis of this protection.