Publications

  1. Polymorphic residues in HLA-B that mediate HIV control distinctly modulate peptide interactions with both TCR and KIR molecules.

    Tano-Menka R, Singh NK, Muzhingi I, Li X, Mandanas MV, Kaseke C, Crain CR, Zhang A, Ogunshola FJ, Vecchiarello L, Piechocka-Trocha A, Bashirova A, Birnbaum ME, Carrington M, Walker BD, Gaiha GD. Structure. 2024 Aug 8;32(8):1121-1136.e5. doi: 10.1016/j.str.2024.04.015. Epub 2024 May 10. PMID: 38733995 

     

  2. Expanded Antigen-Specific Elimination Assay to Measure Human CD8+ T Cell Cytolytic Potential.

    Collins DR, Olatotse MJ, Racenet ZJ, Arshad U, Çakan E, Gaiha GD, Clayton KL, Walker BD.Curr Protoc. 2024 Jul;4(7):e1109. doi: 10.1002/cpz1.1109.PMID: 39023416 

     

  3. Structure-based network analysis predicts pathogenic variants in human proteins associated with inherited retinal disease.

    Hauser BM, Luo Y, Nathan A, Al-Moujahed A, Vavvas DG, Comander J, Pierce EA, Place EM, Bujakowska KM, Gaiha GD, Rossin EJ.NPJ Genom Med. 2024 May 27;9(1):31. doi: 10.1038/s41525-024-00416-w.PMID: 38802398 

  4. Structure-based network analysis predicts mutations associated with inherited retinal disease.

    Hauser BM, Luo Y, Nathan A, Gaiha GD, Vavvas D, Comander J, Pierce EA, Place EM, Bujakowska KM, Rossin EJ.medRxiv [Preprint]. 2023 Jul 6:2023.07.05.23292247. doi: 10.1101/2023.07.05.23292247.Update in: NPJ Genom Med. 2024 May 27;9(1):31. doi: 10.1038/s41525-024-00416-w.PMID: 37461650 

  5. Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers.

    Bricio-Moreno L, Barreto de Albuquerque J, Neary JM, Nguyen T, Kuhn LF, Yeung Y, Hastie KM, Landeras-Bueno S, Olmedillas E, Hariharan C, Nathan A, Getz MA, Gayton AC, Khatri A, Gaiha GD, Ollmann Saphire E, Luster AD, Moon JJ.Front Immunol. 2024 Mar 11;15:1329846. doi: 10.3389/fimmu.2024.1329846. eCollection 2024.PMID: 38529279 

  6. SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency.

    Li Y, Choudhary MC, Regan J, Boucau J, Nathan A, Speidel T, Liew MY, Edelstein GE, Kawano Y, Uddin R, Deo R, Marino C, Getz MA, Reynolds Z, Barry M, Gilbert RF, Tien D, Sagar S, Vyas TD, Flynn JP, Hammond SP, Novack LA, Choi B, Cernadas M, Wallace ZS, Sparks JA, Vyas JM, Seaman MS, Gaiha GD, Siedner MJ, Barczak AK, Lemieux JE, Li JZ.Sci Transl Med. 2024 Jan 24;16(731):eadk1599. doi: 10.1126/scitranslmed.adk1599. Epub 2024 Jan 24.PMID: 38266109 

  7. Viral and host mediators of non-suppressible HIV-1 viremia.

    Mohammadi A, Etemad B, Zhang X, Li Y, Bedwell GJ, Sharaf R, Kittilson A, Melberg M, Crain CR, Traunbauer AK, Wong C, Fajnzylber J, Worrall DP, Rosenthal A, Jordan H, Jilg N, Kaseke C, Giguel F, Lian X, Deo R, Gillespie E, Chishti R, Abrha S, Adams T, Siagian A, Dorazio D, Anderson PL, Deeks SG, Lederman MM, Yawetz S, Kuritzkes DR, Lichterfeld MD, Sieg S, Tsibris A, Carrington M, Brumme ZL, Castillo-Mancilla JR, Engelman AN, Gaiha GD, Li JZ.Nat Med. 2023 Dec;29(12):3212-3223. doi: 10.1038/s41591-023-02611-1. Epub 2023 Nov 13.PMID: 37957382

  8. T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19.

    Zonozi R, Walters LC, Shulkin A, Naranbhai V, Nithagon P, Sauvage G, Kaeske C, Cosgrove K, Nathan A, Tano-Menka R, Gayton AC, Getz MA, Senjobe F, Worrall D, Iafrate AJ, Fromson C, Montesi SB, Rao DA, Sparks JA, Wallace ZS, Farmer JR, Walker BD, Charles RC, Laliberte K, Niles JL, Gaiha GD. Sci Transl Med. 2023 Nov 29;15(724):eadh4529. doi: 10.1126/scitranslmed.adh4529. Epub 2023 Nov 29.PMID: 38019932

     

  9. Features of functional and dysfunctional CD8+ T cells to guide HIV vaccine development.

    Bhattacharyya S, Crain CR, Goldberg B, Gaiha GD. Curr Opin HIV AIDS. 2023 Sep 1;18(5):257-263. doi: 10.1097/COH.0000000000000812. Epub 2023 Jul 18.PMID: 37535040 Review.

  10. SARS-CoV-2 Viral Clearance and Evolution Varies by Extent of Immunodeficiency.

    Li Y, Choudhary MC, Regan J, Boucau J, Nathan A, Speidel T, Liew MY, Edelstein GE, Kawano Y, Uddin R, Deo R, Marino C, Getz MA, Reynold Z, Barry M, Gilbert RF, Tien D, Sagar S, Vyas TD, Flynn JP, Hammond SP, Novack LA, Choi B, Cernadas M, Wallace ZS, Sparks JA, Vyas JM, Seaman MS, Gaiha GD, Siedner MJ, Barczak AK, Lemieux JE, Li JZ.medRxiv [Preprint]. 2023 Aug 7:2023.07.31.23293441. doi: 10.1101/2023.07.31.23293441.Update in: Sci Transl Med. 2024 Jan 24;16(731):eadk1599. doi: 10.1126/scitranslmed.adk1599.PMID: 37577493 

     

  11. Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide.

    Li X, Singh NK, Collins DR, Ng R, Zhang A, Lamothe-Molina PA, Shahinian P, Xu S, Tan K, Piechocka-Trocha A, Urbach JM, Weber JK, Gaiha GD, Takou Mbah OC, Huynh T, Cheever S, Chen J, Birnbaum M, Zhou R, Walker BD, Wang JH.Nat Commun. 2023 May 22;14(1):2929. doi: 10.1038/s41467-023-38573-8.PMID: 37217466 

     

  12. A pan-variant mRNA-LNP T cell vaccine protects HLA transgenic mice from mortality after infection with SARS-CoV-2 Beta.

    Carter B, Huang P, Liu G, Liang Y, Lin PJC, Peng BH, McKay LGA, Dimitrakakis A, Hsu J, Tat V, Saenkham-Huntsinger P, Chen J, Kaseke C, Gaiha GD, Xu Q, Griffiths A, Tam YK, Tseng CK, Gifford DK.Front Immunol. 2023 Mar 9;14:1135815. doi: 10.3389/fimmu.2023.1135815. eCollection 2023.PMID: 36969239 

  13. Comparative Immunogenicity and Effectiveness of mRNA-1273, BNT162b2, and Ad26.COV2.S COVID-19 Vaccines.

    Naranbhai V, Garcia-Beltran WF, Chang CC, Berrios Mairena C, Thierauf JC, Kirkpatrick G, Onozato ML, Cheng J, St Denis KJ, Lam EC, Kaseke C, Tano-Menka R, Yang D, Pavlovic M, Yang W, Kui A, Miller TE, Astudillo MG, Cahill JE, Dighe AS, Gregory DJ, Poznansky MC, Gaiha GD, Balazs AB, Iafrate AJ.J Infect Dis. 2022 Apr 1;225(7):1141-1150. doi: 10.1093/infdis/jiab593.PMID: 34888672 

  14. T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals.

    Naranbhai V, Nathan A, Kaseke C, Berrios C, Khatri A, Choi S, Getz MA, Tano-Menka R, Ofoman O, Gayton A, Senjobe F, Zhao Z, St Denis KJ, Lam EC, Carrington M, Garcia-Beltran WF, Balazs AB, Walker BD, Iafrate AJ, Gaiha GD. Cell. 2022 Mar 17;185(6):1041-1051.e6. doi: 10.1016/j.cell.2022.01.029.

    The SARS-CoV-2 Omicron variant (B.1.1.529) contains mutations that mediate escape from infection and vaccine-induced antibody responses, although the extent to which these substitutions in spike and non-spike proteins affect T cell recognition is unknown. Here we show that T cell responses in individuals with prior infection, vaccination, both prior infection and vaccination, and boosted vaccination are largely preserved to Omicron spike and non-spike proteins. However, we also identify a subset of individuals (∼21%) with a >50% reduction in T cell reactivity to the Omicron spike. Evaluation of functional CD4 + and CD8 + memory T cell responses confirmed these findings and reveal that reduced recognition to Omicron spike is primarily observed within the CD8 + T cell compartment. Booster vaccination substantially enhanced T cell responses to Omicron spike. In contrast to neutralizing immunity, these findings suggest preservation of T cell responses to the Omicron variant, although with reduced reactivity in some individuals.

     

  15. T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all prior infected and vaccinated individuals.

    Naranbhai V, Nathan A, Kaseke C, Berrios C, Khatri A, Choi S, Getz MA, Tano-Menka R, Ofoman O, Gayton A, Senjobe F, Denis KJS, Lam EC, Garcia-Beltran WF, Balazs AB, Walker BD, Iafrate AJ, Gaiha GD.medRxiv [Preprint]. 2022 Jan 5:2022.01.04.21268586. doi: 10.1101/2022.01.04.21268586.Update in: Cell. 2022 Mar 17;185(6):1041-1051.e6. doi: 10.1016/j.cell.2022.01.029.PMID: 35018386 

     

  16. Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia.

    Collins DR, Urbach JM, Racenet ZJ, Arshad U, Power KA, Newman RM, Mylvaganam GH, Ly NL, Lian X, Rull A, Rassadkina Y, Yanez AG, Peluso MJ, Deeks SG, Vidal F, Lichterfeld M, Yu XG, Gaiha GD, Allen TM, Walker BD.Immunity. 2021 Oct 12;54(10):2372-2384.e7. doi: 10.1016/j.immuni.2021.08.007. Epub 2021 Sep 7.PMID: 34496223

     

  17. Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.

    Nathan A, Rossin EJ, Kaseke C, Park RJ, Khatri A, Koundakjian D, Urbach JM, Singh NK, Bashirova A, Tano-Menka R, Senjobe F, Waring MT, Piechocka-Trocha A, Garcia-Beltran WF, Iafrate AJ, Naranbhai V, Carrington M, Walker BD, Gaiha GD.Cell. 2021 Aug 19;184(17):4401-4413.e10. doi: 10.1016/j.cell.2021.06.029. Epub 2021 Jun 30.PMID: 34265281 

    The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape convalescent and vaccine-induced antibody responses has renewed focus on the development of broadly protective T-cell-based vaccines. Here, we apply structure-based network analysis and assessments of HLA class I peptide stability to define mutationally constrained CD8+ T cell epitopes across the SARS-CoV-2 proteome. Highly networked residues are conserved temporally among circulating variants and sarbecoviruses and disproportionately impair spike pseudotyped lentivirus infectivity when mutated. Evaluation of HLA class I stabilizing activity for 18 globally prevalent alleles identifies CD8+ T cell epitopes within highly networked regions with limited mutational frequencies in circulating SARS-CoV-2 variants and deep-sequenced primary isolates. Moreover, these epitopes elicit demonstrable CD8+ T cell reactivity in convalescent individuals but reduced recognition in recipients of mRNA-based vaccines. These data thereby elucidate key mutationally constrained regions and immunogenic epitopes in the SARS-CoV-2 proteome for a global T-cell-based vaccine against emerging variants and SARS-like coronaviruses.

  18. HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV.

    Kaseke C, Park RJ, Singh NK, Koundakjian D, Bashirova A, Garcia Beltran WF, Takou Mbah OC, Ma J, Senjobe F, Urbach JM, Nathan A, Rossin EJ, Tano-Menka R, Khatri A, Piechocka-Trocha A, Waring MT, Birnbaum ME, Baker BM, Carrington M, Walker BD, Gaiha GD. Cell Rep. 2021 Jul 13;36(2):109378. doi: 10.1016/j.celrep.2021.109378.PMID: 34260940 

    Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines.

  19. The Emerging Role for CTL Epitope Specificity in HIV Cure Efforts.

    Kaseke C, Tano-Menka R, Senjobe F, Gaiha GD. J Infect Dis. 2021 Feb 15;223(12 Suppl 2):32-37. doi: 10.1093/infdis/jiaa333.PMID: 33586771 Review.

  20. Oral Biologic Delivery: Advances Toward Oral Subunit, DNA, and mRNA Vaccines and the Potential for Mass Vaccination During Pandemics.

    Coffey JW, Gaiha GD, Traverso G.Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:517-540. doi: 10.1146/annurev-pharmtox-030320-092348. Epub 2020 Aug 31.PMID: 32466690 Review.

     

  21. Dendritic cells focus CTL responses toward highly conserved and topologically important HIV-1 epitopes.

    Garcia-Bates TM, Palma ML, Anderko RR, Hsu DC, Ananworanich J, Korber BT, Gaiha GD, Phanuphak N, Thomas R, Tovanabutra S, Walker BD, Mellors JW, Piazza PA, Kroon E, Riddler SA, Michael NL, Rinaldo CR, Mailliard RB; I4C and RV254 Study Groups.EBioMedicine. 2021 Jan;63:103175. doi: 10.1016/j.ebiom.2020.103175. Epub 2021 Jan 12.PMID: 33450518 

     

  22.  Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host.

    Choi B, Choudhary MC, Regan J, Sparks JA, Padera RF, Qiu X, Solomon IH, Kuo HH, Boucau J, Bowman K, Adhikari UD, Winkler ML, Mueller AA, Hsu TY, Desjardins M, Baden LR, Chan BT, Walker BD, Lichterfeld M, Brigl M, Kwon DS, Kanjilal S, Richardson ET, Jonsson AH, Alter G, Barczak AK, Hanage WP, Yu XG, Gaiha GD, Seaman MS, Cernadas M, Li JZ.N Engl J Med. 2020 Dec 3;383(23):2291-2293. doi: 10.1056/NEJMc2031364. Epub 2020 Nov 11.PMID: 33176080

     

  23. CD8+ T cells in HIV control, cure and prevention.

    Collins DR, Gaiha GD, Walker BD.Nat Rev Immunol. 2020 Aug;20(8):471-482. doi: 10.1038/s41577-020-0274-9. Epub 2020 Feb 12.PMID: 32051540 Review.

     

  24. Structural topology defines protective CD8+ T cell epitopes in the HIV proteome.

    Gaiha GD, Rossin EJ, Urbach J, Landeros C, Collins DR, Nwonu C, Muzhingi I, Anahtar MN, Waring OM, Piechocka-Trocha A, Waring M, Worrall DP, Ghebremichael MS, Newman RM, Power KA, Allen TM, Chodosh J, Walker BD.Science. 2019 May 3;364(6439):480-484. doi: 10.1126/science.aav5095.PMID: 31048489

    Mutationally constrained epitopes of variable pathogens represent promising targets for vaccine design but are not reliably identified by sequence conservation. In this study, we employed structure-based network analysis, which applies network theory to HIV protein structure data to quantitate the topological importance of individual amino acid residues. Mutation of residues at important network positions disproportionately impaired viral replication and occurred with high frequency in epitopes presented by protective human leukocyte antigen (HLA) class I alleles. Moreover, CD8+ T cell targeting of highly networked epitopes distinguished individuals who naturally control HIV, even in the absence of protective HLA alleles. This approach thereby provides a mechanistic basis for immune control and a means to identify CD8+ T cell epitopes of topological importance for rational immunogen design, including a T cell-based HIV vaccine

  25. CD8(+) T Cells and cART: A Dynamic Duo?

    Gaiha GD, Walker BD.Immunity. 2016 Sep 20;45(3):466-468. doi: 10.1016/j.immuni.2016.09.003.PMID: 27653598 Review.

     

  26. Dysfunctional HIV-specific CD8+ T cell proliferation is associated with increased caspase-8 activity and mediated by necroptosis.

    Gaiha GD, McKim KJ, Woods M, Pertel T, Rohrbach J, Barteneva N, Chin CR, Liu D, Soghoian DZ, Cesa K, Wilton S, Waring MT, Chicoine A, Doering T, Wherry EJ, Kaufmann DE, Lichterfeld M, Brass AL, Walker BD.Immunity. 2014 Dec 18;41(6):1001-12. doi: 10.1016/j.immuni.2014.12.011. Epub 2014 Dec 8.PMID: 25526311 

     

  27. Comprehensive identification of host modulators of HIV-1 replication using multiple orthologous RNAi reagents.

    Zhu J, Davoli T, Perriera JM, Chin CR, Gaiha GD, John SP, Sigiollot FD, Gao G, Xu Q, Qu H, Pertel T, Sims JS, Smith JA, Baker RE, Maranda L, Ng A, Elledge SJ, Brass AL.Cell Rep. 2014 Oct 23;9(2):752-66. doi: 10.1016/j.celrep.2014.09.031. Epub 2014 Oct 16. PMID: 25373910 

  28. Immunology. The fiery side of HIV-induced T cell death.

    Gaiha GD, Brass AL.Science. 2014 Jan 24;343(6169):383-4. doi: 10.1126/science.1250175.PMID: 24458634 

     

  29. Surfactant Protein D modulates HIV infection of both T-cells and dendritic cells.

    Madsen J, Gaiha GD, Palaniyar N, Dong T, Mitchell DA, Clark HW.PLoS One. 2013;8(3):e59047. doi: 10.1371/journal.pone.0059047. Epub 2013 Mar 18.PMID: 23527085 

     

  30. Reactivation of latent HIV-1 by inhibition of BRD4.

    Zhu J, Gaiha GD, John SP, Pertel T, Chin CR, Gao G, Qu H, Walker BD, Elledge SJ, Brass AL.Cell Rep. 2012 Oct 25;2(4):807-16. doi: 10.1016/j.celrep.2012.09.008. Epub 2012 Oct 4.PMID: 23041316 

     

  31. IFITM3 inhibits influenza A virus infection by preventing cytosolic entry.

    Feeley EM, Sims JS, John SP, Chin CR, Pertel T, Chen LM, Gaiha GD, Ryan BJ, Donis RO, Elledge SJ, Brass AL.PLoS Pathog. 2011 Oct;7(10):e1002337. doi: 10.1371/journal.ppat.1002337. Epub 2011 Oct 27.PMID: 22046135 

     

  32. Surfactant protein A binds to HIV and inhibits direct infection of CD4+ cells, but enhances dendritic cell-mediated viral transfer.

    Gaiha GD, Dong T, Palaniyar N, Mitchell DA, Reid KB, Clark HW.J Immunol. 2008 Jul 1;181(1):601-9. doi: 10.4049/jimmunol.181.1.601.PMID: 18566427