Enhancing SIV Vaccine Protection in Non-Human Primates
Author Information
Author(s): Hirao Lauren A., Hokey David A., Morrow Matthew P., Jure-Kunkel Maria N., Weiner David B.
Primary Institution: University of Pennsylvania
Hypothesis
A blocking antibody directed toward CTLA-4 will provide expansion primarily of a more T helper phenotype while an antibody that serves as a 4-1BB agonist will provide more of a late costimulatory signal associated with the induction of an effector T cell phenotype.
Conclusion
The study shows that the use of 4-1BB as an adjuvant significantly enhances the immune response and control of SIV replication compared to CTLA-4 blockade.
Supporting Evidence
- Animals receiving the 4-1BB mAb exhibited enhanced IFN-γ responses compared to the DNA vaccine only group.
- The combination of both mAbs enhanced the magnitude of the polyfunctional CD8+ T cell response.
- Following challenge, the group that received both mAbs exhibited a significant, ∼2.0 log, decrease in plasma viral load compared to the naïve group.
- More than half the animals receiving 4-1BB antibodies alone or in combination with CTLA-4 antibodies were able to completely suppress viral replication.
Takeaway
This study tested two different treatments to help a vaccine work better against a virus in monkeys, finding that one treatment helped the immune system fight the virus much more effectively.
Methodology
Cynomolgus macaques were immunized with SIV DNA vaccines and treated with monoclonal antibodies targeting CTLA-4 and 4-1BB to evaluate their effects on immune responses and viral load after SIV challenge.
Potential Biases
Potential bias in the selection of treatment groups and the interpretation of immune response data.
Limitations
The study was conducted in a non-human primate model, which may not fully replicate human responses.
Participant Demographics
Thirty cynomolgus macaques, consisting of 11 females and 19 males, aged 3 to 8 years.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website