Immune Responses To HIV And Other Pathogens

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Daniel Cesar Douek
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $912,355
Funding agency: National Institute of Allergy and Infectious Diseases

In this project we use next generation sequencing approaches to sequence the adaptive immune receptors of antigen-specific B cells and T cells. The sequencing is increasingly at the single cell level and paired with whole transcriptome analysis. We do this in the context of vaccination, natural infection and mouse models of cancer. The aim is to understand the nature of effective antigen-specific adaptive immune responses. We have implemented the 10x Genomics Chromium platform as well as an in-house SMART-seq protocol. We have successfully developed and implemented a custom primer library prep approach so that we may adapt the standard 10x 5 immunoglobulin and T cell receptor sequencing protocol for use with samples from rhesus and cynomolgus macaques, and Guinea pigs. In addition, we have increased the sensitivity of the library prep by 100-fold by removing the fragmentation step. We have implemented CITE-seq applications using custom conjugated antibodies to perform high parameter cell surface proteomics. All of these approaches have been used to investigate the nature and evolution of antigen-specific T cell and antibody responses in HIV, COVID-19, cancer, and influenza in natural infection and after vaccination.

Terms: <AIDS Virus><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Antibody Response><Antigen Receptors><Antigens><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><CITE sequencing><CITE-seq><CITEseq><COVID-19><CV-19><Cancer Model><CancerModel><Cancers><Cavia><Cell Body><Cell surface><Cells><Cellular Indexing of Transcriptomes and Epitopes by Sequencing><Chromium><Coronavirus Infectious Disease 2019><Cr element><Crab-Eating Macaque><Crab-Eating Monkey><Custom><Cynomolgus Monkey><Cynomolgus macaque><Evolution><Genomics><Grippe><Guinea Pigs><Guinea Pigs Mammals><HIV><Human Immunodeficiency Viruses><Immune><Immune Globulins><Immune response><Immunes><Immunoglobulins><Immunologic Receptors><Immunological Receptors><Immunological response><Infection><Influenza><LAV-HTLV-III><Libraries><Lymphadenopathy-Associated Virus><M fascicularis><M mulatta><M. fascicularis><M. mulatta><Macaca fascicularis><Macaca mulatta><Malignant Neoplasms><Malignant Tumor><NGS Method><NGS system><Nature><Proteomics><Protocol><Protocols documentation><Rhesus Macaque><Rhesus Monkey><Sampling><T cell receptor repertoire sequencing><T cell receptor sequencing><T-Cells><T-Lymphocyte><TCR repertoire sequencing><TCR sequencing><TCR-seq><TCRseq><Vaccination><Virus-HIV><adaptive immune response><antibody conjugate><antigen-specific T cells><cellular indexing of transcriptomes and epitopes by single cell sequencing><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><customs><global gene expression><global transcription profile><host response><immune receptor><immune system response><immunogen><immunoresponse><malignancy><mouse model><murine model><neoplasm/cancer><next gen sequencing><next generation sequencing><nextgen sequencing><pathogen><response><thymus derived lymphocyte><transcriptome><transcriptomics>