Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth
A vaccine will likely be one of the key tools for ending the HIV-1/AIDS epidemic by preventing HIV-1 spread within uninfected populations and achieving a cure for people living with HIV-1. The currently prevailing view of the vaccine field is to introduce protective antibodies, nevertheless, a vacci...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/3/360 |
| _version_ | 1797563251932790784 |
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| author | Nathifa Moyo Edmund G. Wee Bette Korber Kapil Bahl Samantha Falcone Sunny Himansu Adrianne L. Wong Antu K. Dey Mark Feinberg Tomáš Hanke |
| author_facet | Nathifa Moyo Edmund G. Wee Bette Korber Kapil Bahl Samantha Falcone Sunny Himansu Adrianne L. Wong Antu K. Dey Mark Feinberg Tomáš Hanke |
| author_sort | Nathifa Moyo |
| collection | DOAJ |
| description | A vaccine will likely be one of the key tools for ending the HIV-1/AIDS epidemic by preventing HIV-1 spread within uninfected populations and achieving a cure for people living with HIV-1. The currently prevailing view of the vaccine field is to introduce protective antibodies, nevertheless, a vaccine to be effective may need to harness protective T cells. We postulated that focusing a T-cell response on the most vulnerable regions of the HIV-1 proteome while maximizing a perfect match between the vaccine and circulating viruses will control HIV-1 replication. We currently use a combination of replication-deficient simian (chimpanzee) adenovirus and poxvirus modified vaccinia virus Ankara to deliver bivalent conserved-mosaic immunogens to human volunteers. Here, we exploit the mRNA platform by designing tetravalent immunogens designated as HIVconsvM, and demonstrate that mRNA formulated in lipid nanoparticles induces potent, broad and polyfunctional T-cell responses in a pre-clinical model. These results support optimization and further development of this vaccine strategy in experimental medicine trials in humans. |
| first_indexed | 2024-03-10T18:39:57Z |
| format | Article |
| id | doaj.art-c6a3f4acd94640fab6a5e393110fa76d |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T18:39:57Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-c6a3f4acd94640fab6a5e393110fa76d2023-11-20T05:57:51ZengMDPI AGVaccines2076-393X2020-07-018336010.3390/vaccines8030360Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and BreadthNathifa Moyo0Edmund G. Wee1Bette Korber2Kapil Bahl3Samantha Falcone4Sunny Himansu5Adrianne L. Wong6Antu K. Dey7Mark Feinberg8Tomáš Hanke9The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKLos Alamo National Laboratory, Theoretical Biology and Biophysics, Los Alamos, NM 87545, USAModerna Inc., Cambridge, MA 02139, USAModerna Inc., Cambridge, MA 02139, USAModerna Inc., Cambridge, MA 02139, USAInternational AIDS Vaccine Initiative-New York, New York, NY 10004, USAInternational AIDS Vaccine Initiative-New York, New York, NY 10004, USAInternational AIDS Vaccine Initiative-New York, New York, NY 10004, USAThe Jenner Institute, University of Oxford, Oxford OX3 7DQ, UKA vaccine will likely be one of the key tools for ending the HIV-1/AIDS epidemic by preventing HIV-1 spread within uninfected populations and achieving a cure for people living with HIV-1. The currently prevailing view of the vaccine field is to introduce protective antibodies, nevertheless, a vaccine to be effective may need to harness protective T cells. We postulated that focusing a T-cell response on the most vulnerable regions of the HIV-1 proteome while maximizing a perfect match between the vaccine and circulating viruses will control HIV-1 replication. We currently use a combination of replication-deficient simian (chimpanzee) adenovirus and poxvirus modified vaccinia virus Ankara to deliver bivalent conserved-mosaic immunogens to human volunteers. Here, we exploit the mRNA platform by designing tetravalent immunogens designated as HIVconsvM, and demonstrate that mRNA formulated in lipid nanoparticles induces potent, broad and polyfunctional T-cell responses in a pre-clinical model. These results support optimization and further development of this vaccine strategy in experimental medicine trials in humans.https://www.mdpi.com/2076-393X/8/3/360HIV vaccineHIVconsvXHIVconsvconserved regionsT cell vaccinemRNA vaccines |
| spellingShingle | Nathifa Moyo Edmund G. Wee Bette Korber Kapil Bahl Samantha Falcone Sunny Himansu Adrianne L. Wong Antu K. Dey Mark Feinberg Tomáš Hanke Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth Vaccines HIV vaccine HIVconsvX HIVconsv conserved regions T cell vaccine mRNA vaccines |
| title | Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth |
| title_full | Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth |
| title_fullStr | Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth |
| title_full_unstemmed | Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth |
| title_short | Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth |
| title_sort | tetravalent immunogen assembled from conserved regions of hiv 1 and delivered as mrna demonstrates potent preclinical t cell immunogenicity and breadth |
| topic | HIV vaccine HIVconsvX HIVconsv conserved regions T cell vaccine mRNA vaccines |
| url | https://www.mdpi.com/2076-393X/8/3/360 |
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