Programming cytomegalovirus as an HIV vaccine

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Cytomegalovirus (CMV) was developed as a vaccine vector to induce tissue-resident CD8+ T cells for early interception of HIV/SIV infection.
• This strategy aimed to position effector T cells for immediate response to nascent viral challenges.

Purpose of the Study:

• To investigate the potential of non-human primate (NHP) CMV vectors to elicit distinct CD8+ T cell responses.
• To evaluate the efficacy of different T cell responses, including MHC-E restricted ones, in controlling SIV infection.

Main Methods:

• Programming NHP CMV vectors to elicit CD8+ T cell responses recognizing viral peptides via MHC-Ia, MHC-II, and/or MHC-E.
• Assessing the protective capacity of these engineered T cell responses against pathogenic SIV challenge.

Main Results:

• CMV vectors successfully pre-positioned effector CD8+ T cells in tissues.
• NHP CMV vectors could be programmed to elicit differential CD8+ T cell responses restricted by MHC-Ia, MHC-II, or MHC-E.
• MHC-E-restricted CD8+ T cell responses uniquely achieved stringent arrest and clearance of highly pathogenic SIV.

Conclusions:

• CMV-elicited MHC-E-restricted CD8+ T cells represent a functionally distinct and potent immune response.
• This approach demonstrates unprecedented vaccine-mediated protection against SIV, suggesting potential for superior efficacy against HIV-1.
• The findings highlight the potential of CMV vectors and MHC-E restricted T cells for combating infectious diseases and cancers.