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

Author

Naranbhai, Vivek, Nathan, Anusha, Kaseke, Clarety, Berrios, Cristhian, Khatri, Ashok, Choi, Shawn, Getz, Matthew A., Tano-Menka, Rhoda, Ofoman, Onosereme, Gayton, Alton, Senjobe, Fernando, Zhao, Zezhou, St Denis, Kerri J., Lam, Evan C., Carrington, Mary, Garcia-Beltran, Wilfredo F., Balazs, Alejandro B., Walker, Bruce D., Iafrate, A. John, and Gaiha, Gaurav D.

Published
2022
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2. Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses

Author

Nathan, Anusha, Rossin, Elizabeth J., Kaseke, Clarety, Park, Ryan J., Khatri, Ashok, Koundakjian, Dylan, Urbach, Jonathan M., Singh, Nishant K., Bashirova, Arman, Tano-Menka, Rhoda, Senjobe, Fernando, Waring, Michael T., Piechocka-Trocha, Alicja, Garcia-Beltran, Wilfredo F., Iafrate, A. John, Naranbhai, Vivek, Carrington, Mary, Walker, Bruce D., and Gaiha, Gaurav D.

Published
2021
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3. HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV

Author

Kaseke, Clarety, Park, Ryan J., Singh, Nishant K., Koundakjian, Dylan, Bashirova, Arman, Garcia Beltran, Wilfredo F., Takou Mbah, Overbeck C., Ma, Jiaqi, Senjobe, Fernando, Urbach, Jonathan M., Nathan, Anusha, Rossin, Elizabeth J., Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T., Birnbaum, Michael E., Baker, Brian M., Carrington, Mary, Walker, Bruce D., and Gaiha, Gaurav D.

Published
2021
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4. T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19

Author

Zonozi, Reza, primary, Walters, Lucy C., additional, Shulkin, Aaron, additional, Naranbhai, Vivek, additional, Nithagon, Pravarut, additional, Sauvage, Gabriel, additional, Kaeske, Clarety, additional, Cosgrove, Katherine, additional, Nathan, Anusha, additional, Tano-Menka, Rhoda, additional, Gayton, Alton C., additional, Getz, Matthew A., additional, Senjobe, Fernando, additional, Worrall, Daniel, additional, Iafrate, A. John, additional, Fromson, Caroline, additional, Montesi, Sydney B., additional, Rao, Deepak A., additional, Sparks, Jeffrey A., additional, Wallace, Zachary S., additional, Farmer, Jocelyn R., additional, Walker, Bruce D., additional, Charles, Richelle C., additional, Laliberte, Karen, additional, Niles, John L., additional, and Gaiha, Gaurav D., additional

Published
2023
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5. T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all prior infected and vaccinated individuals

Author

Naranbhai, Vivek, primary, Nathan, Anusha, additional, Kaseke, Clarety, additional, Berrios, Cristhian, additional, Khatri, Ashok, additional, Choi, Shawn, additional, Getz, Matthew A., additional, Tano-Menka, Rhoda, additional, Ofoman, Onosereme, additional, Gayton, Alton, additional, Senjobe, Fernando, additional, Denis, Kerri J. St, additional, Lam, Evan C., additional, Garcia-Beltran, Wilfredo F., additional, Balazs, Alejandro B., additional, Walker, Bruce D., additional, Iafrate, A. John, additional, and Gaiha, Gaurav D., additional

Published
2022
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6. Preferential expansion upon boosting of cross-reactive “pre-existing” switched memory B cells that recognize the SARS-CoV-2 Omicron variant Spike protein

Author

Perugino, Cory A., primary, Liu, Hang, additional, Feldman, Jared, additional, Hauser, Blake M., additional, Jacob-Dolan, Catherine, additional, Nathan, Anusha, additional, Zhou, Zezhou, additional, Kaseke, Clarety, additional, Tano-Menka, Rhoda, additional, Getz, Matthew A., additional, Senjobe, Fernando, additional, Berrios, Cristhian, additional, Ofoman, Onosereme, additional, Lemieux, Jacob E., additional, Goldberg, Marcia B., additional, Nundel, Kerstin, additional, Moormann, Ann, additional, Marshak-Rothstein, Ann, additional, Iafrate, John A., additional, Gaiha, Gaurav, additional, Charles, Richelle, additional, Balazs, Alejandro B., additional, Naranbhai, Vivek, additional, Schmidt, Aaron G., additional, and Pillai, Shiv, additional

Published
2022
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7. HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV

Author

Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Biology, Kaseke, Clarety, Park, Ryan J, Singh, Nishant K, Koundakjian, Dylan, Bashirova, Arman, Garcia Beltran, Wilfredo F, Takou Mbah, Overbeck C, Ma, Jiaqi, Senjobe, Fernando, Urbach, Jonathan M, Nathan, Anusha, Rossin, Elizabeth J, Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T, Birnbaum, Michael E, Baker, Brian M, Carrington, Mary, Walker, Bruce D, Gaiha, Gaurav D, Koch Institute for Integrative Cancer Research at MIT, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Massachusetts Institute of Technology. Department of Biology, Kaseke, Clarety, Park, Ryan J, Singh, Nishant K, Koundakjian, Dylan, Bashirova, Arman, Garcia Beltran, Wilfredo F, Takou Mbah, Overbeck C, Ma, Jiaqi, Senjobe, Fernando, Urbach, Jonathan M, Nathan, Anusha, Rossin, Elizabeth J, Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T, Birnbaum, Michael E, Baker, Brian M, Carrington, Mary, Walker, Bruce D, and Gaiha, Gaurav D

Abstract

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.

Published
2021

11. Conformational changes in the Ebola virus membrane fusion machine induced by pH, Ca2+, and receptor binding.

Author

Das, Dibyendu Kumar, Bulow, Uriel, Diehl, William E., Durham, Natasha D., Senjobe, Fernando, Chandran, Kartik, Luban, Jeremy, and Munro, James B.

Subjects
MEMBRANE fusion, EBOLA virus, VIRAL envelope proteins, FLUORESCENCE resonance energy transfer, VIRAL envelopes
Abstract

The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for virus entry into cells. Following endocytosis of EBOV, the GP1 domain is cleaved by cellular cathepsins in acidic endosomes, removing the glycan cap and exposing a binding site for the Niemann-Pick C1 (NPC1) receptor. NPC1 binding to cleaved GP1 is required for entry. How this interaction translates to GP2 domain-mediated fusion of viral and endosomal membranes is not known. Here, using a bulk fluorescence dequenching assay and single-molecule Förster resonance energy transfer (smFRET)-imaging, we found that acidic pH, Ca2+, and NPC1 binding synergistically induce conformational changes in GP2 and permit virus-liposome lipid mixing. Acidic pH and Ca2+ shifted the GP2 conformational equilibrium in favor of an intermediate state primed for NPC1 binding. Glycan cap cleavage on GP1 enabled GP2 to transition from a reversible intermediate to an irreversible conformation, suggestive of the postfusion 6-helix bundle; NPC1 binding further promoted transition to the irreversible conformation. Thus, the glycan cap of GP1 may allosterically protect against inactivation of EBOV by premature triggering of GP2. The Ebola virus envelope glycoprotein is a membrane fusion machine required for the virus to enter into host cells. This study presents direct observation of the conformational changes that the envelope glycoprotein undergoes during the membrane fusion process. [ABSTRACT FROM AUTHOR]

Published
2020
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12. HLA class-I-peptide stability mediates CD8+T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV

Author

Kaseke, Clarety, Park, Ryan J., Singh, Nishant K., Koundakjian, Dylan, Bashirova, Arman, Garcia Beltran, Wilfredo F., Takou Mbah, Overbeck C., Ma, Jiaqi, Senjobe, Fernando, Urbach, Jonathan M., Nathan, Anusha, Rossin, Elizabeth J., Tano-Menka, Rhoda, Khatri, Ashok, Piechocka-Trocha, Alicja, Waring, Michael T., Birnbaum, Michael E., Baker, Brian M., Carrington, Mary, Walker, Bruce D., and Gaiha, Gaurav D.

Abstract

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.

Published
2021
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13. T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all prior infected and vaccinated individuals.

Author

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, and Gaiha GD

Abstract

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.

Published
2022
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