Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques
© 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 ch...
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| Format: | Article |
| Language: | English |
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Proceedings of the National Academy of Sciences
2021
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| Online Access: | https://hdl.handle.net/1721.1/133471 |
| _version_ | 1826203116134989824 |
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| author | Murakowski, Dariusz K Barton, John P Peter, Lauren Chandrashekar, Abishek Bondzie, Esther Gao, Ang Barouch, Dan H Chakraborty, Arup K |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Murakowski, Dariusz K Barton, John P Peter, Lauren Chandrashekar, Abishek Bondzie, Esther Gao, Ang Barouch, Dan H Chakraborty, Arup K |
| author_sort | Murakowski, Dariusz K |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T12:31:54Z |
| format | Article |
| id | mit-1721.1/133471 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T12:31:54Z |
| publishDate | 2021 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1334712024-03-20T19:55:36Z Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques Murakowski, Dariusz K Barton, John P Peter, Lauren Chandrashekar, Abishek Bondzie, Esther Gao, Ang Barouch, Dan H Chakraborty, Arup K 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 © 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. 2021-10-27T19:53:01Z 2021-10-27T19:53:01Z 2021 2021-06-08T17:36:03Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133471 en 10.1073/PNAS.2022496118 Proceedings of the National Academy of Sciences of the United States of America 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. application/pdf Proceedings of the National Academy of Sciences PNAS |
| spellingShingle | Murakowski, Dariusz K Barton, John P Peter, Lauren Chandrashekar, Abishek Bondzie, Esther Gao, Ang Barouch, Dan H Chakraborty, Arup K Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques |
| title | Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques |
| title_full | Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques |
| title_fullStr | Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques |
| title_full_unstemmed | Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques |
| title_short | Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques |
| title_sort | adenovirus vectored vaccine containing multidimensionally conserved parts of the hiv proteome is immunogenic in rhesus macaques |
| url | https://hdl.handle.net/1721.1/133471 |
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