Tetravalent Immunogen Assembled from Conserved Regions of HIV-1 and Delivered as mRNA Demonstrates Potent Preclinical T-Cell Immunogenicity and Breadth

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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Main Authors: Nathifa Moyo, Edmund G. Wee, Bette Korber, Kapil Bahl, Samantha Falcone, Sunny Himansu, Adrianne L. Wong, Antu K. Dey, Mark Feinberg, Tomáš Hanke
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Vaccines
Subjects:
HIV vaccine
HIVconsvX
HIVconsv
conserved regions
T cell vaccine
mRNA vaccines
Online Access:https://www.mdpi.com/2076-393X/8/3/360
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spelling doaj-c6a3f4acd94640fab6a5e393110fa76d2020-11-25T03:13:11ZengMDPI AGVaccines2076-393X2020-07-01836036010.3390/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
collection DOAJ
language English
format Article
sources DOAJ
author Nathifa Moyo
Edmund G. Wee
Bette Korber
Kapil Bahl
Samantha Falcone
Sunny Himansu
Adrianne L. Wong
Antu K. Dey
Mark Feinberg
Tomáš Hanke
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
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
title 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_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_sort tetravalent immunogen assembled from conserved regions of hiv-1 and delivered as mrna demonstrates potent preclinical t-cell immunogenicity and breadth
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2020-07-01
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.
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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AT tomashanke tetravalentimmunogenassembledfromconservedregionsofhiv1anddeliveredasmrnademonstratespotentpreclinicaltcellimmunogenicityandbreadth
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