The Sette lab’s previous large scale epitope identification efforts (supported by HHS contracts) have led to a deeper understanding of the role of T cells and HLA variants in the development of (or protection from) DENV disease. Current efforts (supported in part by a consortium grant led by Eva Harris at UC Berkeley) addresses questions including whether infection with different serotypes is associated with distinct types of T cell responses, whether any HLA alleles are associated with pathogenesis or protection, and whether vaccination with a formulation in clinical trials is associated with T cell responses similar to those following infection that might serve as correlates of protection.
Selected References
Kallas EG, Precioso AR, Palacios R, et al. Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial [published online ahead of print, 2020 Mar 24]. Lancet Infect Dis. 2020;S1473-3099(20)30023-2. doi:10.1016/S1473-3099(20)30023-2
Graham N, Eisenhauer P, Diehl SA, et al. Rapid Induction and Maintenance of Virus-Specific CD8+ TEMRA and CD4+ TEM Cells Following Protective Vaccination Against Dengue Virus Challenge in Humans. Front Immunol. 2020;11:479. Published 2020 Mar 24. doi:10.3389/fimmu.2020.00479
Grifoni A, Voic H, Dhanda SK, Kidd CK, Brien JD, Buus S, Stryhn A, Durbin AP, Whitehead S, Diehl SA, De Silva AD, Balmaseda A, Harris E, Weiskopf D, Sette A. T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species. J Virol. 2020 Mar 4. pii: JVI.00089-20. doi: 10.1128/JVI.00089-20. [Epub ahead of print] PubMed PMID: 32132233.
Grifoni A, Pham J, Sidney J, O’Rourke PH, Paul S, Peters B, Martini SR, de Silva AD, Ricciardi MJ, Magnani DM, Silveira CGT, Maestri A, Costa PR, de-Oliveira-Pinto LM, de Azeredo EL, Damasco PV, Phillips E, Mallal S, de Silva AM, Collins M, Durbin A, Diehl SA, Cerpas C, Balmaseda A, Kuan G, Coloma J, Harris E, Crowe JE Jr, Stone M, Norris PJ, Busch M, Vivanco-Cid H, Cox J, Graham BS, Ledgerwood JE, Turtle L, Solomon T, Kallas EG, Watkins DI, Weiskopf D, Sette A. Prior Dengue Virus Exposure Shapes T Cell Immunity to Zika Virus in Humans. J Virol. 2017 Nov 30;91(24). pii: e01469-17. doi: 10.1128/JVI.01469-17. Print 2017 Dec 15. PubMed PMID: 28978707; PubMed Central PMCID: PMC5709580.
Tian Y, Babor M, Lane J, Schulten V, Patil VS, Seumois G, Rosales SL, Fu Z, Picarda G, Burel J, Zapardiel-Gonzalo J, Tennekoon RN, De Silva AD, Premawansa S, Premawansa G, Wijewickrama A, Greenbaum JA, Vijayanand P, Weiskopf D, Sette A, Peters B. Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA. Nat Commun. 2017 Nov 13;8(1):1473. doi: 10.1038/s41467-017-01728-5. PubMed PMID: 29133794; PubMed Central PMCID: PMC5684192.
Weiskopf D, Angelo MA, Grifoni A, O’Rourke PH, Sidney J, Paul S, De Silva AD, Phillips E, Mallal S, Premawansa S, Premawansa G, Wijewickrama A, Peters B, Sette A. HLA-DRB1 Alleles Are Associated With Different Magnitudes of Dengue Virus-Specific CD4+ T-Cell Responses. J Infect Dis. 2016 Oct 1;214(7):1117-24. doi: 10.1093/infdis/jiw309. Epub 2016 Jul 20. PubMed PMID: 27443615; PubMed Central PMCID: PMC5021234.
Dan JM, Lindestam Arlehamn CS, Weiskopf D, da Silva Antunes R, Havenar-Daughton C, Reiss SM, Brigger M, Bothwell M, Sette A, Crotty S. A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood. J Immunol. 2016 Aug 1;197(3):983-93. doi: 10.4049/jimmunol.1600318. Epub 2016 Jun 24. PubMed PMID: 27342848; PubMed Central PMCID: PMC4955771.
Weiskopf D, Bangs DJ, Sidney J, Kolla RV, De Silva AD, de Silva AM, Crotty S, Peters B, Sette A. Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4256-63. doi: 10.1073/pnas.1505956112. Epub 2015 Jul 20. PubMed PMID: 26195744; PubMed Central PMCID: PMC4534238.
Weiskopf D, Angelo MA, Bangs DJ, Sidney J, Paul S, Peters B, de Silva AD, Lindow JC, Diehl SA, Whitehead S, Durbin A, Kirkpatrick B, Sette A. The human CD8+ T cell responses induced by a live attenuated tetravalent dengue vaccine are directed against highly conserved epitopes. J Virol. 2015 Jan;89(1):120-8. doi: 10.1128/JVI.02129-14. Epub 2014 Oct 15. PubMed PMID: 25320311; PubMed Central PMCID: PMC4301095.
Weiskopf D, Angelo MA, Sidney J, Peters B, Shresta S, Sette A. Immunodominance changes as a function of the infecting dengue virus serotype and primary versus secondary infection. J Virol. 2014 Oct;88(19):11383-94. doi: 10.1128/JVI.01108-14. Epub 2014 Jul 23. PubMed PMID: 25056881; PubMed Central PMCID: PMC4178794.
Weiskopf D, Angelo MA, de Azeredo EL, Sidney J, Greenbaum JA, Fernando AN, Broadwater A, Kolla RV, De Silva AD, de Silva AM, Mattia KA, Doranz BJ, Grey HM, Shresta S, Peters B, Sette A. Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells. Proc Natl Acad Sci. 2013 May 28;110(22):E2046-53.