Immune phenotyping of human immune responses to SARS CoV-2 vaccination and infection

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: Florian  Krammer
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2022
Award: $283,216
Funding agency: National Institute of Allergy and Infectious Diseases

Summary
SARS-CoV-2 vaccines have been developed in record time and are now widely used in many different
countries around the globe. Project 1 will focus on characterizing immune signatures associated with
SARS-CoV-2 immunization using different vaccine types. In Aim 1 we will leverage existing
biospecimen collected before and after vaccination with mRNA-based or adenoviral vector-based
vaccines to investigate the durability and breadth of vaccine-induced antibody responses and to
determine how early innate immune profiles influence humoral and cell-mediated adaptive immunity
following SARS-CoV-2 vaccination. In Aim 2 we will characterize the immune responses specific for
break-through infections, despite vaccination with in-depth cellular characterization of selected cases
experiencing severe COVID-19. In Aim 3 we will also determine the immune responses in vaccinated
individuals who get infected and in individuals experiencing vaccine-associated side effects and
reactogenicity. Lastly, in Aim 4, the observations made in human cohorts will be validated in the human
primary tonsillar explant model system, by treating these histocultures (HC) ex vivo with the different
vaccine types, which will allow us to identify the cells that take up the vaccine preparations as well as
those critical for mounting efficient immune defenses. For all these studies, specimens will be facilitated
by the Clinical Core and with the assistance of the Immune Phenotyping Core and the Genomics
Core, all data generated will be analyzed by the Data Management and Dissemination Core.
Integrated analyses of data from different types of specimens using different techniques will be also
performed by the Data Management and Analysis Core, which will identify unique signatures for each
vaccine platform. Collectively, these studies will contribute to defining the biological correlates of
vaccine induced immune protection in the context of SARS-CoV-2 immunization.

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