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Published on: May 2, 2011
Enhanced safety and efficacy of live attenuated SIV vaccines by prevaccination with recombinant vaccines
1Department of Veterinary Pathology, Microbiology, and Immunology, University of California, Davis 95616, USA.
Abstract:
The only vaccines shown to be protective against intravenous challenge with virulent virus in the simian immunodeficiency virus (SIV)/macaque model are attenuated live SIVs. However, these vaccines have several disadvantages: 1) they persist indefinitely in vaccinated macaques; 2) they are pathogenic to neonatal macaques; and 3) they are lethal in some adult macaques. To enhance the safety and efficacy of these vaccines, we immunized macaques first with recombinant vaccines and then inoculated the animals with SIV(delta(nef)). In the first experiment, preimmunized macaques advanced to disease slower than controls after challenge with virulent SIV; five animals survived for 3 years without disease and only the vaccine virus (SIV(delta(nef)) could be isolated at this time. In the second experiment, preimmunized animals had lower virus loads and no disease compared to controls.
Insights
Recombinant vaccines followed by live attenuated simian immunodeficiency virus (SIV) enhance vaccine safety and efficacy. This approach protected macaques against virulent SIV challenge, reducing disease progression and viral load.
Area of Science:
- Veterinary immunology
- Vaccinology
- Primate models of infectious disease
Background:
- Attenuated live simian immunodeficiency virus (SIV) vaccines are protective but have safety concerns, including persistence, pathogenicity in neonates, and lethality in adults.
- Live attenuated SIV vaccines pose risks due to their indefinite persistence, pathogenicity in neonatal macaques, and potential lethality in adult macaques.
Purpose of the Study:
- To enhance the safety and efficacy of SIV vaccines.
- To evaluate a prime-boost vaccination strategy using recombinant vaccines followed by live attenuated SIV.
Main Methods:
- Macaques were immunized with recombinant vaccines.
- Immunized macaques were subsequently inoculated with a live attenuated SIV vaccine (SIV(delta(nef))).
- Animals were challenged with virulent SIV, and outcomes were compared to control groups.
Main Results:
- Pre-immunization with recombinant vaccines followed by SIV(delta(nef)) vaccination led to slower disease progression after virulent SIV challenge.
- Five out of nine macaques survived for 3 years without disease, with only the vaccine virus (SIV(delta(nef))) isolated.
- In a second experiment, pre-immunized animals exhibited lower viral loads and no disease compared to controls.
Conclusions:
- A prime-boost strategy using recombinant vaccines followed by live attenuated SIV enhances vaccine safety and efficacy.
- This approach offers a promising alternative to live attenuated SIV vaccines alone for preventing SIV infection in macaques.
- Further research into this prime-boost strategy could advance the development of safer and more effective SIV/HIV vaccines.
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