Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy-Reference-Cited by-同舟云学术

Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy

Published:2021-04-30 Issue:6541 Volume:372 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Verweij Marieke C.¹^ORCID,Hansen Scott G.¹^ORCID,Iyer Ravi¹^ORCID,John Nessy¹^ORCID,Malouli Daniel¹^ORCID,Morrow David¹^ORCID,Scholz Isabel¹^ORCID,Womack Jennie¹^ORCID,Abdulhaqq Shaheed¹^ORCID,Gilbride Roxanne M.¹,Hughes Colette M.¹,Ventura Abigail B.¹^ORCID,Ford Julia C.¹^ORCID,Selseth Andrea N.¹^ORCID,Oswald Kelli²,Shoemaker Rebecca²,Berkemeier Brian²^ORCID,Bosche William J.²^ORCID,Hull Michael²,Shao Jason³^ORCID,Sacha Jonah B.¹,Axthelm Michael K.¹^ORCID,Edlefsen Paul T.³^ORCID,Lifson Jeffrey D.²^ORCID,Picker Louis J.¹^ORCID,Früh Klaus¹^ORCID

Affiliation:

1. Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.

2. AIDS and Cancer Virus Program, Frederick National Laboratory, Frederick, MD 21702, USA.

3. Population Sciences and Computational Biology Programs, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Abstract

Viral peptide is key to T cell priming Simian immunodeficiency virus (SIV) vaccines containing a strain 68-1 rhesus cytomegalovirus (RhCMV) vector elicit strong CD8 + T cell responses that can control and clear SIV infections. The SIV peptides targeted by these T cells are presented on major histocompatibility complex (MHC) II and the nonclassical MHC-Ib molecule MHC-E rather than the more typical MHC-Ia. Verweij et al. show that the 68-1 RhCMV–encoded peptide VL9 drives intracellular transport of MHC-E and recognition of RhCMV-infected targets by MHC-E–restricted CD8 + T cells. Rhesus macaques vaccinated with a mutant 68-1 RhCMV lacking VL9 showed no priming of MHC-E–restricted CD8 + T cells and no protection against SIV. This work strongly suggests that future effective CMV-based HIV vaccines in humans will also require MHC-E–restricted CD8 + T cell priming. Science , this issue p. eabe9233

Funder

National Institutes of Health

NIH Office of the Director

National Cancer Institute

National Institute of Allergy and Infectious Diseases

Bill and Melinda Gates Foundation

Bill and Melinda Gates Foundation supported Collaboration for AIDS Vaccine Discovery

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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