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Multicolor Flow Cytometry Analyses of Cellular Immune Response in Rhesus Macaques
Published on: April 22, 2010
Recombinant rubella vectors elicit SIV Gag-specific T cell responses with cytotoxic potential in rhesus macaques
Margherita Rosati1, Candido Alicea2, Viraj Kulkarni2
1Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA.
Abstract:
Live-attenuated rubella vaccine strain RA27/3 has been demonstrated to be safe and immunogenic in millions of children. The vaccine strain was used to insert SIV gag sequences and the resulting rubella vectors were tested in rhesus macaques alone and together with SIV gag DNA in different vaccine prime-boost combinations. We previously reported that such rubella vectors induce robust and durable SIV-specific humoral immune responses in macaques. Here, we report that recombinant rubella vectors elicit robust de novo SIV-specific cellular immune responses detectable for >10 months even after a single vaccination. The antigen-specific responses induced by the rubella vector include central and effector memory CD4(+) and CD8(+) T cells with cytotoxic potential. Rubella vectors can be administered repeatedly even after vaccination with the rubella vaccine strain RA27/3. Vaccine regimens including rubella vector and SIV gag DNA in different prime-boost combinations resulted in robust long-lasting cellular responses with significant increase of cellular responses upon boost. Rubella vectors provide a potent platform for inducing HIV-specific immunity that can be combined with DNA in a prime-boost regimen to elicit durable cellular immunity.
Insights
Recombinant rubella vectors effectively induce long-lasting SIV-specific cellular immunity in macaques, even after a single dose. Combining rubella vectors with DNA prime-boost regimens enhances these durable immune responses.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Live-attenuated rubella vaccine strain RA27/3 is safe and immunogenic.
- Rubella vectors were engineered to express SIV gag sequences.
Purpose of the Study:
- To evaluate the ability of recombinant rubella vectors to induce SIV-specific cellular immune responses.
- To assess the durability and characteristics of these responses in rhesus macaques.
- To investigate the efficacy of prime-boost regimens combining rubella vectors and SIV gag DNA.
Main Methods:
- Rhesus macaques were vaccinated with rubella vectors expressing SIV gag sequences, alone or with SIV gag DNA, in various prime-boost combinations.
- SIV-specific cellular immune responses, including CD4(+) and CD8(+) T cell responses, were analyzed.
- Immune responses were monitored for over 10 months.
Main Results:
- Recombinant rubella vectors elicited robust de novo SIV-specific cellular immune responses lasting over 10 months after a single vaccination.
- Responses included central and effector memory CD4(+) and CD8(+) T cells with cytotoxic potential.
- Prime-boost regimens with rubella vectors and SIV gag DNA induced robust, long-lasting cellular immunity, with enhanced responses upon boosting.
Conclusions:
- Rubella vectors are a potent platform for inducing HIV-specific cellular immunity.
- Repeated administration of rubella vectors is feasible, even after prior vaccination with RA27/3.
- Combining rubella vectors with DNA prime-boost regimens offers a promising strategy for eliciting durable cellular immunity.
