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In vivo and in vitro immunogenicity of novel MHC class I presented epitopes to confer protective immunity against chronic HTLV-1 infection
Journal article   Open access   Peer reviewed

In vivo and in vitro immunogenicity of novel MHC class I presented epitopes to confer protective immunity against chronic HTLV-1 infection

Ria Mulherkar, Aykan Karabudak, Rashida Ginwala, Xiaofang Huang, Aileen Rowan, Ramila Philip, Edward L. Murphy, Danielle Clements, Lishomwa C. Ndhlovu, Zafar K. Khan, …
Vaccine, v 36(33), pp 5046-5057
09 Aug 2018
DOI: https://doi.org/10.1016/j.vaccine.2018.07.002
PMID: 30005946
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc6091894View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

ATLL Epitopes HAM/TSP HTLV-1 Immunoproteomics Vaccine
•HTLV-1 is a potentially seriously disabling virus for which there is currently no cure or vaccine.•Immunoproteomics can identify naturally presented epitopes in infected individuals.•We confirmed 6 novel epitopes presented in chronically infected patients.•In vitro and in vivo generated epitope-specific CD8 cells showed immunogenicity.•Results contribute to creation of a therapeutic peptide-based vaccine for HTLV-1. Human T-cell leukemia virus type 1 (HTLV-1) has infected as many as 10 million people worldwide. While 90% are asymptomatic, 5% develop severe diseases including adult T-cell leukemia/lymphoka (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). No vaccine against HTLV-1 exists, and screening programs are not universal. However, patients with chronic HTLV-1 infection have high frequencies of HTLV-1-activated CD8+ T cells, and the two main HLA alleles (A2, A24) are present in 88% of infected individuals. We thus utilized an immunoproteomics approach to characterize MHC-I restricted epitopes presented by HLA-A2+, A24+ MT-2 and SLB-1 cell lines. Unlike traditional motif prediction algorithms, this approach identifies epitopes associated with cytotoxic T-cell responses in their naturally processed forms, minimizing differences in antigen processing and protein expression levels. Out of nine identified peptides, we confirmed six novel MHC-I restricted epitopes that were capable of binding HLA-A2 and HLA-A24 alleles and used in vitro and in vivo methods to generate CD8+ T cells specific for each of these peptides. MagPix MILLIPLEX data showed that in vitro generated epitope-specific CD8+ T cells secreted IFN-ɣ, granzyme B, MIP-1α, TNF-α, perforin and IL-10 when cultured in the presence of MT-2 cell line. Degranulation assay confirmed cytotoxic response through surface expression of CD107 on CD8+ T cells when cultured with MT-2 cells. A CD8+ T-cell killing assay indicated significant antiviral activity of CD8+ T cells specific against all identified peptides. In vivo generated CD8+ T cells similarly demonstrated immunogenicity on ELISpot, CD107 degranulation assay, and MagPix MILLIPLEX analysis. These epitopes are thus candidates for a therapeutic peptide-based vaccine against HTLV-1, and our results provide preclinical data for the advancement of such a vaccine.

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14 citations in Web of Science
15 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Industry collaboration
Domestic collaboration
International collaboration
Web of Science research areas
Immunology
Medicine, Research & Experimental
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