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Increased valency of conserved-mosaic vaccines enhances the breadth and depth of epitope recognition

Increased valency of conserved-mosaic vaccines enhances the breadth and depth of epitope recognition
Increased valency of conserved-mosaic vaccines enhances the breadth and depth of epitope recognition
The biggest roadblock in development of effective vaccines against human immunodeficiency virus type 1 (HIV-1) is the virus genetic diversity. For T-cell vaccine, this can be tackled by focusing the vaccine-elicited T-cells on the highly functionally conserved regions of HIV-1 proteins, mutations in which typically cause a replicative fitness loss, and by computing multivalent mosaic proteins, which maximize the coverage of potential 9-mer T-cell epitopes of the input viral sequences. Our first conserved region vaccines HIVconsv employed clade alternating consensus sequences and showed promise in the initial clinical trials in terms of magnitude and breadth of elicited CD8(+) T-cells. Here, monitoring T-cells restricted by HLA-A*02:01 in transgenic mice, we assessed whether or not the tHIVconsv design (HIVconsv with a tissue plasminogen activator leader sequence) benefits from combining with a complementing conserved mosaic immunogen tHIVcmo, and compared the bivalent immunization to that with trivalent conserved mosaic vaccines. A hierarchy of tHIVconsv ? tHIVconsv+tHIVcmo < tCmo1+tCmo2+tCmo3 vaccinations for induction of CD8(+) T-cell responses was observed in terms of recognition of tested peptide variants. Thus, our HLA-A*02:01-restricted epitope data concur with previously published mouse and macaque observations and suggest that even conserved region vaccines benefit from oligovalent mosaic design.
1525-0016
375-384
Abdul-Jawad, Sultan
75c35bac-9434-489c-922f-1a4062cf30df
Ondondo, Beatrice
302233c2-694a-4460-87b1-d4aefd6bb63f
Van Hateren, Andy
e345fa3c-d89c-4b91-947e-c1d818cc7f71
Gardner, Andrew
c440553f-4ff6-4c84-8161-bb186a8b3ba8
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Korber, Bette
e166e2e3-8515-48db-92ae-cb57fbb17f70
Hanke, Tomáš
5e76b76f-443c-4613-a9fd-fefe0b66a288
Abdul-Jawad, Sultan
75c35bac-9434-489c-922f-1a4062cf30df
Ondondo, Beatrice
302233c2-694a-4460-87b1-d4aefd6bb63f
Van Hateren, Andy
e345fa3c-d89c-4b91-947e-c1d818cc7f71
Gardner, Andrew
c440553f-4ff6-4c84-8161-bb186a8b3ba8
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Korber, Bette
e166e2e3-8515-48db-92ae-cb57fbb17f70
Hanke, Tomáš
5e76b76f-443c-4613-a9fd-fefe0b66a288

Abdul-Jawad, Sultan, Ondondo, Beatrice, Van Hateren, Andy, Gardner, Andrew, Elliott, Tim, Korber, Bette and Hanke, Tomáš (2016) Increased valency of conserved-mosaic vaccines enhances the breadth and depth of epitope recognition. Molecular Therapy, 24 (2), 375-384. (doi:10.1038/mt.2015.210). (PMID:26581160)

Record type: Article

Abstract

The biggest roadblock in development of effective vaccines against human immunodeficiency virus type 1 (HIV-1) is the virus genetic diversity. For T-cell vaccine, this can be tackled by focusing the vaccine-elicited T-cells on the highly functionally conserved regions of HIV-1 proteins, mutations in which typically cause a replicative fitness loss, and by computing multivalent mosaic proteins, which maximize the coverage of potential 9-mer T-cell epitopes of the input viral sequences. Our first conserved region vaccines HIVconsv employed clade alternating consensus sequences and showed promise in the initial clinical trials in terms of magnitude and breadth of elicited CD8(+) T-cells. Here, monitoring T-cells restricted by HLA-A*02:01 in transgenic mice, we assessed whether or not the tHIVconsv design (HIVconsv with a tissue plasminogen activator leader sequence) benefits from combining with a complementing conserved mosaic immunogen tHIVcmo, and compared the bivalent immunization to that with trivalent conserved mosaic vaccines. A hierarchy of tHIVconsv ? tHIVconsv+tHIVcmo < tCmo1+tCmo2+tCmo3 vaccinations for induction of CD8(+) T-cell responses was observed in terms of recognition of tested peptide variants. Thus, our HLA-A*02:01-restricted epitope data concur with previously published mouse and macaque observations and suggest that even conserved region vaccines benefit from oligovalent mosaic design.

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Accepted/In Press date: 9 November 2015
e-pub ahead of print date: 5 January 2016
Published date: 24 February 2016
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 393773
URI: http://eprints.soton.ac.uk/id/eprint/393773
ISSN: 1525-0016
PURE UUID: f3c600d4-534c-4d11-92a6-04fd37a48a96
ORCID for Andy Van Hateren: ORCID iD orcid.org/0000-0002-3915-0239
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

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Date deposited: 04 May 2016 11:28
Last modified: 15 Mar 2024 03:27

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Contributors

Author: Sultan Abdul-Jawad
Author: Beatrice Ondondo
Author: Andrew Gardner
Author: Tim Elliott ORCID iD
Author: Bette Korber
Author: Tomáš Hanke

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