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Principal Investigator: Andres Chang
Organization: EMORY UNIVERSITY
Fiscal Year: 2024
Award: $192,888
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients have immune system deficits
that arise from the cancer and are aggravated by lymphoma therapies, placing them at higher risk of morbidity
and mortality after infection with viruses like influenza and severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2). Patients are strongly recommended to get vaccinated and boosted with SARS-CoV-2 mRNA
vaccines, but antibody responses after vaccination in these patients are often impaired. SARS-CoV-2 vaccines
also elicit T cell responses in healthy individuals that may be protective but previous studies indicate that T cells
from NHL/CLL patients are also dysfunctional.
Under the mentorship of Drs. Rafi Ahmed and Jonathon Cohen, I have assembled a cohort of over 600 NHL/CLL
patients with over 1,300 longitudinal blood samples paired with clinical data that I have used to study the immune
responses in this patient population. Using this cohort, I showed that most patients have lower antibody
responses after SARS-CoV-2 vaccination than otherwise healthy individuals and that antibody responses
correlate at least partly with lymphoma therapies. I have also shown that some patients produce spike-specific
CD4+ and CD8+ T cells after vaccination. The longitudinal, antigen-specific CD4+ and CD8+ T cell responses
after vaccination and infection have not been well characterized in NHL/CLL patients. I hypothesize that these
patients have alterations in their CD4+ and CD8+ T cell responses after antigen stimulation, which are dependent
on the underlying lymphoma subtype and lymphoma therapy.
This proposal has 3 goals: 1) To evaluate the generation, differentiation, breadth, and persistence of SARS-
CoV-2-specific CD4+ T cell responses in NHL/CLL patients after vaccination and infection using functional
assays and single cell sequencing technologies; 2) To define the primary and memory SARS-CoV-2-specific
CD8+ T cell responses after vaccination and infection through functional assays and single cell sequencing
technologies; and 3) to support my transition from a trainee in Dr. Ahmed’s laboratory to leading an independent
research program.
Successful completion of these studies will provide in-depth knowledge of the generation, evolution, breadth,
and persistence of antigen-specific T cell responses in NHL/CLL patients after vaccination and infection. This
knowledge will facilitate the design of interventions that may improve vaccine responses in these and other
immunosuppressed patients, protecting them from potentially life-threatening viral infections like SARS-CoV-2
and influenza. Moreover, the insights on the generation and maintenance of adaptive immune responses against
novel antigens obtained from these studies could help fuel the development of better cancer immunotherapies.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><ATAC sequencing><ATAC-seq><ATACseq><Activities of Daily Living><Activities of everyday life><Antibodies><Antibody Response><Antigens><Assay><Assay for Transposase-Accessible Chromatin using sequencing><B blood cells><B cell><B cell depletion therapy><B cell directed therapy><B cell targeted therapy><B cell therapies><B cell therapy><B cells><B-Cell CLL><B-Cell Chronic Lymphocytic Leukemia><B-Cell Chronic Lymphogenous Leukemia><B-Cell Chronic Lymphoid Leukemia><B-Cell Lymphocytic Leukemia><B-Cell NHL><B-Cell Non-Hodgkin's Lymphoma><B-Cell NonHodgkins Lymphoma><B-Cells><B-Lymphocytes><B-Lymphocytic Leukemia><B-cell><Bioassay><Biological Assay><Blood><Blood Reticuloendothelial System><Blood Sample><Blood specimen><Booster Immunization><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><CITE sequencing><CITE-seq><CITEseq><COVID-19 immune response><COVID-19 infection><COVID-19 vaccination><COVID-19 vaccine><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Cancers><Cell Body><Cell Mediated Immunology><Cell Therapy><Cell-Mediated Immunity><Cells><Cellular Immunity><Cellular Indexing of Transcriptomes and Epitopes by Sequencing><Cessation of life><Chromatin><Chronic B-Lymphocytic Leukemia><Chronic Lymphatic Leukemia><Chronic Lymphoblastic Leukemia><Chronic Lymphocytic Leukemia><Chronic Lymphogenous Leukemia><Clinical Data><CoV-2><CoV2><Combined Modality Therapy><Data><Death><Development><Dysfunction><Evolution><Functional disorder><Gene Transcription><Generations><Genetic Transcription><Germinoblastic Sarcoma><Germinoblastoma><Goals><Grippe><Histocompatibility Complex><Histocompatibility Complices><Immune memory><Immune response><Immune system><Immunocompromised><Immunocompromised Host><Immunocompromised Patient><Immunologic Memory><Immunological Memory><Immunological response><Immunosuppressed Host><Impairment><Individual><Infection><Influenza><Knowledge><LYT3><Label><Laboratories><Life><Lymph Node Reticuloendothelial System><Lymph node proper><Lymphatic nodes><Lymphoma><Maintenance><Major Histocompatibility Complex><Major Histocompatibility Complices><Malignant Lymphoma><Malignant Neoplasms><Malignant Tumor><Memory><Mentorship><Morbidity><Morbidity - disease rate><Multimodal Therapy><Multimodal Treatment><Non-Hodgkin's Lymphoma><Nonhodgkins Lymphoma><Nucleocapsid><Patients><Peptides><Phenotype><Physiopathology><Publishing><RNA Expression><RNA vaccine><RNA-based vaccine><Recommendation><Research><Reticulolymphosarcoma><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 immune response><SARS-CoV-2 infection><SARS-CoV-2 vaccination><SARS-CoV-2 vaccine><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Secondary Immunization><Serology><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 immune response><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Single cell seq><Staining method><Stains><T cell receptor repertoire sequencing><T cell receptor sequencing><T cell response><T-Cell Lymphoma><T-Cell Non-Hodgkin's Lymphoma><T-Cell NonHodgkins Lymphoma><T-Cell and NK-Cell Non-Hodgkin's Lymphoma><T-Cells><T-Lymphocyte><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><TCR repertoire sequencing><TCR sequencing><TCR-seq><TCRseq><Technology><Tissue Sample><Transcription><Vaccinated><Vaccination><Vaccinee><Vaccines><Variant><Variation><Viral><Viral Diseases><Virus><Virus Diseases><Vulnerable Populations><Wuhan coronavirus><adaptive immune response><anamnestic reaction><anti-cancer immunotherapy><anticancer immunotherapy><antigen-specific T cells><assay for transposase accessible chromatin followed by sequencing><assay for transposase accessible chromatin seq><assay for transposase accessible chromatin sequencing><assay for transposase-accessible chromatin with sequencing><booster dose><booster shot><booster vaccination><booster vaccine><cancer immunotherapy><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular indexing of transcriptomes and epitopes by single cell sequencing><cellular therapeutic><cellular therapy><chronic lymphoid leukemia><cohort><combination therapy><combined modality treatment><combined treatment><coronavirus disease 2019 immune response><coronavirus disease 2019 infection><coronavirus disease 2019 vaccination><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19 vaccine><coronavirus disease-19 virus><cytokine><daily living function><daily living functionality><design><designing><developmental><functional ability><functional capacity><hCoV19><high risk><host response><immune response to vaccination><immune response to vaccines><immune system response><immune-based cancer therapies><immunogen><immunoresponse><immunosuppressed><immunosuppressed patient><immunotherapy for cancer><immunotherapy of cancer><improved><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><insight><intervention design><leukemia treatment><leukemic therapy><lymph gland><lymph nodes><lymphnodes><mRNA vaccine><mRNA-based vaccine><malignancy><malignant lymphocyte><mortality><multi-modal therapy><multi-modal treatment><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><neoplasm/cancer><non-Hodgkins disease><novel><pathophysiology><patient population><prevent><preventing><programs><response><secondary immune response><single cell next generation sequencing><single cell sequencing><therapeutic vaccine><therapy design><thymus derived lymphocyte><treatment design><treatment vaccines><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine associated immune response><vaccine boost><vaccine candidates against SARS-CoV-2><vaccine efficacy><vaccine for novel coronavirus><vaccine for the treatment><vaccine for treatment><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccine response><vaccine responsiveness><vaccine-induced response><vaccines preventing COVID><vaccines to prevent COVID><viral infection><virus infection><virus-induced disease><vulnerable group><vulnerable individual><vulnerable people>