Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells
By D. Weiskopf, Michael A. Angelo, E. D. de Azeredo, John Sidney, J. Greenbaum, A. Fernando, Anne H. Broadwater, Ravi V. Kolla, A. D. de Silva, A. D. de Silva and 6 more. Proceedings of the National Academy of Sciences of the United States of America, 2013
607 citations recorded by the source corpus.
Significance Dengue virus is the etiologic agent of dengue fever, the most significant mosquito-borne viral disease in humans, affecting over 100 million individuals each year. Currently there is no licensed vaccine or effective antiviral therapy available, and treatment is largely supportive in nature. This study presents a comprehensive analysis of functional T-cell memory against dengue viruses and suggests an HLA-linked protective role for CD8+ T cells. This demonstration of the protective role of T-cell responses points the way forward to identifying robust correlates of protection in natural immunity and vaccination against dengue virus. The role of CD8+ T cells in dengue virus infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing individuals to severe disease. A comprehensive analysis of CD8+ responses in the general population from the Sri Lankan hyperendemic area, involving the measurement of ex vivo IFNγ responses associated with more than 400 epitopes, challenges the original antigenic sin theory. Although skewing of responses toward primary infecting viruses was detected, this was not associated with impairment of responses either qualitatively or quantitatively. Furthermore, we demonstrate higher magnitude and more polyfunctional responses for HLA alleles associated with decreased susceptibility to severe disease, suggesting that a vigorous response by multifunctional CD8+ T cells is associated with protection from dengue virus disease.
Subfields: Infectious Diseases, Public Health, Environmental and Occupational Health
View Paper: https://www.semanticscholar.org/paper/399f9affcae6c2a10ca4e09a3be92e4f93ebb9d6
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In Infectious Diseases
Citations in the corpus
- COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning (2020, background): “The MHC-I and MHC-II reference alleles covered a wide range of human genetic variation representing the majority of the world population (81, 82).”
- Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals (2020, unknown): “20C. Peripheral blood mononuclear cells (PBMC) were isolated by density-gradient sedimentation using Ficoll-Paque (Lymphoprep, Nycomed Pharma, Oslo, Norway) as previously described (Weiskopf et al., 2013).”
- Properties of MHC Class I Presented Peptides That Enhance Immunogenicity (2013, background): “tested the immune responses to Dengue-derived peptides in Dengue seropositive donors [56].”
- A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2 (2020, methodology): “Following a previously validated approach (Weiskopf et al., 2013), we assembled a set of the 12 most prominent HLA class I alleles that have been shown to allow broad coverage of the general population, as described in the STAR Methods (see also Table S5).”
- The Immune Epitope Database and Analysis Resource in Epitope Discovery and Synthetic Vaccine Design (2017, background): “The third strategy is to pick peptides with percentile ranks below 1% (27).”