The longevity and nature of the anti-SARS-CoV-2 cellular and humoral immune responses

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

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Principal Investigator: Michel C Nussenzweig
Organization: ROCKEFELLER UNIVERSITY
Fiscal Year: 2022
Award: $1,454,501
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary
 The COVID-19 pandemic is currently gripping the world. Aside from the health consequences, the necessary
decrease in human activity has resulted in economic losses without modern precedent, especially in the
developing world where health care and sanitation were not sufficient even prior to the pandemic. Little is known
about the durability of the human immune responses to SARS-CoV-2. A better understanding of the evolution
and persistence of anti SARS-CoV-2 immunity in individuals who recover for the infection or who are vaccinated
are critically needed as they will guide future vaccine efforts.
 The Nussenzweig/Caskey laboratory studied the initial humoral and cellular immune responses of a cohort
of COVID-19 convalescent individuals. These samples were characterized by a series of assays that measure:
1. Serum levels of binding antibodies to the SARS-CoV-2 spike protein (S) and the receptor binding domain
(RBD) and 2. Neutralizing activity against HIV-1 and VSV SARS-CoV-2 pseudotyped viruses and authentic
SARS-CoV-2. In addition, we cloned and characterized the antibodies produced by these individuals and
developed an understanding of the neutralizing epitopes on the RBD. The results showed that the initial humoral
responses to SARS-CoV-2 are highly variable but that nearly all individuals develop some level of neutralizing
activity. Neutralizing activity in serum decreases after by a factor of 5 after 6.2 months. In contrast memory B
cell responses continue to evolve and remain largely intact. Interestingly, there was a convergence of antibody
responses to SARS-CoV-2 that could be explained by structural analysis. In addition to natural infection, a cohort
of volunteers that received the Moderna and Pfizer vaccines was recruited. The B lymphocytes and the
antibodies they produce will be analyzed longitudinally.
 The hypothesis to be tested is that humoral immunity to SARS-CoV-2 infection or mRNA vaccination will
decrease in parallel, but that B cell memory responses will diverge. The overall goal of this proposal is to
determine the longevity and nature of the anti-SARS-CoV-2 cellular and humoral immune responses by re-
examining the same cohort of individuals who either recovered from COVID-19 or received an mRNA vaccine.
The results will inform our understanding of the evolution and persistence of anti- SARS-CoV-2 immunity in
recovered and vaccinated individuals and will inform ongoing and future vaccine efforts.

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