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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Prior infection with a nonpathogenic chimeric simian-human immunodeficiency virus does not efficiently protect
1Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Abstract:
Prior infection with a nef-deleted simian immunodeficiency virus (SIV) protects macaques not only against a homologous pathogenic SIV challenge but also against challenge with a chimeric SIV expressing a human immunodeficiency virus type 1 env gene (SHIV). Since this SHIV is itself nonpathogenic, we sought to explore the use of a nonpathogenic SHIV as a live, attenuated AIDS virus vaccine. Four cynomolgus monkeys infected for greater than 600 days with a chimeric virus composed of SIVmac 239 expressing the human immunodeficiency virus type 1 HXBc2 env, tat, and rev genes were challenged intravenously with 100 animal infectious doses of the J5 clone of SIVmac 32H, an isolate derived by in vivo passage of SIVmac 251. Three of the four monkeys became infected with SIVmac. This observation underlines the difficulty, even with a live virus vaccine, in protecting against an AIDS virus infection.
Insights
A live, attenuated simian immunodeficiency virus (SIV) vaccine protected macaques against homologous SIV but not a pathogenic SIV challenge. This highlights challenges in developing effective AIDS virus vaccines.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Prior infection with nef-deleted simian immunodeficiency virus (SIV) confers protection against homologous SIV and chimeric SIV (SHIV).
- Nonpathogenic SHIV has been explored as a potential live, attenuated AIDS virus vaccine candidate.
Purpose of the Study:
- To evaluate the efficacy of a nonpathogenic SHIV as a live, attenuated AIDS virus vaccine in cynomolgus monkeys.
Main Methods:
- Four cynomolgus monkeys, infected for over 600 days with a SHIV (SIVmac 239 expressing HIV-1 env, tat, and rev genes), were challenged intravenously.
- The challenge inoculum was 100 animal infectious doses of the J5 clone of SIVmac 32H.
Main Results:
- Three out of four vaccinated monkeys became infected following challenge with SIVmac.
- This indicates limited protection conferred by the live, attenuated SHIV vaccine against a pathogenic SIV challenge.
Conclusions:
- Developing effective AIDS virus vaccines remains a significant challenge.
- Live, attenuated vaccines may not provide complete protection against pathogenic simian immunodeficiency virus infection.
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