Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques
Name
e2022496118.full.pdf
Description
Published version
Size
930 KB
Format
Adobe PDF
Checksum (MD5)
39e21938218d1f6ab114371827618344
Author(s)
Murakowski, Dariusz K
Barton, John P
Peter, Lauren
Chandrashekar, Abishek
Bondzie, Esther
Gao, Ang
Barouch, Dan H
Chakraborty, Arup K
Date Issued
2021
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Version
Final published version
Abstract
© 2021 National Academy of Sciences. All rights reserved. An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mutations that can partially restore the fitness cost of immune-evading mutations. Based on the fitness landscapes of HIV proteins that account for the effects of coupled mutations, we designed a single long peptide immunogen comprising parts of the HIV proteome wherein mutations are likely to be deleterious regardless of the sequence of the rest of the viral protein. This immunogen was then stably expressed in adenovirus vectors that are currently in clinical development. Macaques immunized with these vaccine constructs exhibited T-cell responses that were comparable in magnitude to animals immunized with adenovirus vectors with whole HIV protein inserts. Moreover, the T-cell responses in immunized macaques strongly targeted regions contained in our immunogen. These results suggest that further studies aimed toward using our vaccine construct for HIV prophylaxis and cure are warranted.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
10.1073/PNAS.2022496118
https://doi.org/10.1073/PNAS.2022496118
