GagCM9-Specific CD8+ T Cells Do Not Suppress SIV Replication In Vivo
Author Information
Author(s): Vojnov Lara, Martins Mauricio A., Almeida Jorge R., Ende Zachary, Rakasz Eva G., Reynolds Matthew R., Leon Enrique J., Weisgrau Kim L., Burwitz Benjamin J., Folkvord Joy M., Veloso de Santana Marlon G., Costa Neves Patrícia C., Connick Elizabeth, Skinner Pamela J., Gostick Emma, O'Connor David H., Wilson Nancy A., Bonaldo Myrna C., Galler Ricardo, Price David A., Douek Danny C., Watkins David I.
Primary Institution: University of Wisconsin-Madison
Hypothesis
Why do GagCM9-specific CD8+ T cells fail to control SIV replication in vaccinated rhesus macaques?
Conclusion
Despite high levels of GagCM9-specific CD8+ T cells, the vaccinated animals failed to control SIV replication.
Supporting Evidence
- Six out of seven vaccinated animals had high levels of GagCM9-specific CD8+ T cells but could not control viral replication.
- The number of public TCR clonotypes in GagCM9-specific CD8+ T cells inversely correlated with chronic phase viral load.
- Vaccinated animals had a high effector to target ratio of GagCM9-specific CD8+ T cells to SIV-producing cells.
- Despite high frequencies of GagCM9-specific CD8+ T cells, viral loads were comparable to mock-vaccinated controls.
- Viral escape mutations were not observed until later in the infection, indicating that the T cell response was not ineffective due to escape.
Takeaway
Scientists gave seven monkeys a vaccine to help them fight a virus, but even though the monkeys had a lot of immune cells ready to fight, they still couldn't stop the virus from spreading.
Methodology
The study involved vaccinating rhesus macaques with a segment of SIV Gag and then challenging them with SIV to assess the immune response and viral load.
Potential Biases
Potential bias in the selection of animals and the specific immune responses measured.
Limitations
The study was limited to a small sample size of seven animals and focused on a specific T cell response.
Participant Demographics
Indian rhesus macaques (Macaca mulatta), Mamu-A*01+ genotype.
Statistical Information
P-Value
0.0213
Statistical Significance
p=0.0213
Digital Object Identifier (DOI)
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