Programming cytomegalovirus as an HIV vaccine

Louis J. Picker; Jeffrey D. Lifson; Michael Gale; Scott G. Hansen; Klaus Früh

doi:10.1016/j.it.2023.02.001

Programming cytomegalovirus as an HIV vaccine

Louis J. Picker
, Jeffrey D. Lifson
, Michael Gale
, Scott G. Hansen
, Klaus Früh

Research output: Contribution to journal › Review article › peer-review

40 Scopus citations

Abstract

The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, CD8⁺ T cells in tissues for immediate immune interception of nascent primary infection. This goal was achieved and also led to the unexpected discoveries that non-human primate (NHP) CMVs can be programmed to differentially elicit CD8⁺ T cell responses that recognize viral peptides via classical MHC-Ia, and/or MHC-II, and/or MHC-E, and that MHC-E-restricted CD8⁺ T cell responses can uniquely mediate stringent arrest and subsequent clearance of highly pathogenic SIV, an unprecedented type of vaccine-mediated protection. These discoveries delineate CMV vector-elicited MHC-E-restricted CD8⁺ T cells as a functionally distinct T cell response with the potential for superior efficacy against HIV-1, and possibly other infectious agents or cancers.

Original language	English (US)
Pages (from-to)	287-304
Number of pages	18
Journal	Trends in Immunology
Volume	44
Issue number	4
DOIs	https://doi.org/10.1016/j.it.2023.02.001
State	Published - Apr 1 2023

Funding

This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI124377 , U19 AI128741 , RO1 AI059457 , and PO1 AI174856 , by P51 OD011092-61 , and by the Bill and Melinda Gates Foundation grant OPP1107409, and, in part, by federal funds from the National Cancer Institute , National Institutes of Health , under Contract No. 75N91019D00024/HHSN261201500003I (J.D.L.), and from contract number HHSN272201300010C (M.G.). The work summarized here would not have been possible without the help of numerous colleagues over the years. We are particularly grateful to Daniel Malouli, Meaghan Hancock, Jonah Sacha, Ben Bimber, Jay Nelson, Daniel Streblow, and their coworkers for their substantial contributions to this program, including the collaborative generation of unpublished data referred to in this reveiw.Moreover, we thank our colleagues at Vir Biotechnology, Inc. for the clinical development and testing of this new vector platform. Finally, the authors thank K. Rothstein for editing and A. Townsend for figure preparation. This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI124377, U19 AI128741, RO1 AI059457, and PO1 AI174856, by P51 OD011092-61, and by the Bill and Melinda Gates Foundation grant OPP1107409, and, in part, by federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024/HHSN261201500003I (J.D.L.), and from contract number HHSN272201300010C (M.G.). The work summarized here would not have been possible without the help of numerous colleagues over the years. We are particularly grateful to Daniel Malouli, Meaghan Hancock, Jonah Sacha, Ben Bimber, Jay Nelson, Daniel Streblow, and their coworkers for their substantial contributions to this program, including the collaborative generation of unpublished data referred to in this reveiw.Moreover, we thank our colleagues at Vir Biotechnology, Inc. for the clinical development and testing of this new vector platform. Finally, the authors thank K. Rothstein for editing and A. Townsend for figure preparation. L.J.P. S.G.H. and K.F. have a substantial financial interest in Vir Biotechnology, Inc. a company that may have a commercial interest in the results of this research and technology. L.J.P. S.G.H. and K.F. are also consultants to Vir Biotechnology, Inc. These potential individual and institutional conflicts of interest have been reviewed and managed by Oregon Health and Science University (OHSU).

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	75N91019D00024/HHSN261201500003I, HHSN272201300010C
National Institute of Health-National Cancer Institute
National Institute of Allergy and Infectious Diseases	PO1 AI174856, UM1 AI124377, P51 OD011092-61, U19 AI128741, RO1 AI059457
Bill and Melinda Gates Foundation	OPP1107409
Oregon State University/Oregon Health and Science University
Vir Biotechnology

Keywords

HIV vaccine
SIV replication arrest
cytomegalovirus
immune programming

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.it.2023.02.001

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title = "Programming cytomegalovirus as an HIV vaccine",

abstract = "The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, CD8+ T cells in tissues for immediate immune interception of nascent primary infection. This goal was achieved and also led to the unexpected discoveries that non-human primate (NHP) CMVs can be programmed to differentially elicit CD8+ T cell responses that recognize viral peptides via classical MHC-Ia, and/or MHC-II, and/or MHC-E, and that MHC-E-restricted CD8+ T cell responses can uniquely mediate stringent arrest and subsequent clearance of highly pathogenic SIV, an unprecedented type of vaccine-mediated protection. These discoveries delineate CMV vector-elicited MHC-E-restricted CD8+ T cells as a functionally distinct T cell response with the potential for superior efficacy against HIV-1, and possibly other infectious agents or cancers.",

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AU - Lifson, Jeffrey D.

AU - Gale, Michael

AU - Hansen, Scott G.

AU - Früh, Klaus

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N2 - The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, CD8+ T cells in tissues for immediate immune interception of nascent primary infection. This goal was achieved and also led to the unexpected discoveries that non-human primate (NHP) CMVs can be programmed to differentially elicit CD8+ T cell responses that recognize viral peptides via classical MHC-Ia, and/or MHC-II, and/or MHC-E, and that MHC-E-restricted CD8+ T cell responses can uniquely mediate stringent arrest and subsequent clearance of highly pathogenic SIV, an unprecedented type of vaccine-mediated protection. These discoveries delineate CMV vector-elicited MHC-E-restricted CD8+ T cells as a functionally distinct T cell response with the potential for superior efficacy against HIV-1, and possibly other infectious agents or cancers.

AB - The initial development of cytomegalovirus (CMV) as a vaccine vector for HIV/simian immunodeficiency virus (SIV) was predicated on its potential to pre-position high-frequency, effector-differentiated, CD8+ T cells in tissues for immediate immune interception of nascent primary infection. This goal was achieved and also led to the unexpected discoveries that non-human primate (NHP) CMVs can be programmed to differentially elicit CD8+ T cell responses that recognize viral peptides via classical MHC-Ia, and/or MHC-II, and/or MHC-E, and that MHC-E-restricted CD8+ T cell responses can uniquely mediate stringent arrest and subsequent clearance of highly pathogenic SIV, an unprecedented type of vaccine-mediated protection. These discoveries delineate CMV vector-elicited MHC-E-restricted CD8+ T cells as a functionally distinct T cell response with the potential for superior efficacy against HIV-1, and possibly other infectious agents or cancers.

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KW - SIV replication arrest

KW - cytomegalovirus

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Programming cytomegalovirus as an HIV vaccine

Abstract

Funding

Keywords

ASJC Scopus subject areas

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