Cohort-Specific Peptide Reagents Broaden Depth and Breadth Estimates of the CD8 T Cell Response to HIV-1 Gag Potential T Cell Epitopes
Author(s)
Type
Journal Article
Abstract
An effective HIV vaccine will need to stimulate immune responses against the sequence diversity presented in circulating virus strains. In this study, we evaluate breadth and depth estimates of potential T-cell epitopes (PTEs) in transmitted founder virus sequence-derived cohort-specific peptide reagents against reagents representative of consensus and global sequences. CD8 T-cells from twenty-six HIV-1+ PBMC donor samples, obtained at 1-year post estimated date of infection, were evaluated. ELISpot assays compared responses to 15mer consensus (n = 121), multivalent-global (n = 320), and 10mer multivalent cohort-specific (n = 300) PTE peptides, all mapping to the Gag antigen. Responses to 38 consensus, 71 global, and 62 cohort-specific PTEs were confirmed, with sixty percent of common global and cohort-specific PTEs corresponding to consensus sequences. Both global and cohort-specific peptides exhibited broader epitope coverage compared to commonly used consensus reagents, with mean breadth estimates of 3.2 (global), 3.4 (cohort) and 2.2 (consensus) epitopes. Global or cohort peptides each identified unique epitope responses that would not be detected if these peptide pools were used alone. A peptide set designed around specific virologic and immunogenetic characteristics of a target cohort can expand the detection of CD8 T-cell responses to epitopes in circulating viruses, providing a novel way to better define the host response to HIV-1 with implications for vaccine development.
Date Issued
2023-02-17
Date Acceptance
2023-02-13
Citation
Vaccines, 2023, 11 (2)
ISSN
2076-393X
Publisher
MDPI AG
Journal / Book Title
Vaccines
Volume
11
Issue
2
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36851349
PII: vaccines11020472
Subjects
CD8 T-cell
epitope-mapping
HIV-1
HIV-1 vaccine
Publication Status
Published
Coverage Spatial
Switzerland
Article Number
ARTN 472