Innate and Adaptive Immune Responses in SARS-CoV-2 infection (COVID-19)

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: $153,089
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 SARS-CoV-2-specific adaptive immune responses in infected and/or vaccinated humans and non-human primates. 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 NHP models. 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 humans and rhesus macaques. 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 SARS-CoV-2-specific B and T cell responses in SARS-CoV-2 natural infection and after vaccination. In addition, we are studying how microbial products affect immune cell function and systemic inflammation in SARS-CoV-2 infection. We measure inflammatory markers, metabolic markers and microbial nucleic acids in plasma and other body fluids, and we sequence innate immune cell transcriptomes.

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