# Defining humoral correlates of immunity against COVID-19

> **NIH NIH R37** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $391,727

## Abstract

Since 2002, several coronaviruses have emerged able to cause severe respiratory disease, however no vaccine
is available to prevent these rapidly spreading pathogens. Vaccine design has specifically lagged due to our lack
of understanding of the correlates of immunity against these pathogens. Both cellular and humoral immune
responses have been implicated in resolution of disease, but to date only the passive transfer of antibodies has
been shown to confer complete protection in mice. Interestingly, the transfer of both “neutralizing” and non-
neutralizing antibodies have shown protective efficacy, highlighting the role of multiple humoral mechanisms in
limiting viral infection/spread. The precise mechanism of action of these antibodies that have the most profound
impact on limiting disease is currently unclear, but if elucidated could provide critical insights for the development
of effective vaccines against COVID-19 and other coronaviruses. Thus, here we aim to take a systematic
approach to dissect and define both the polyclonal and monoclonal mechanisms by which antibodies confer
protection against COVID-19. Specifically, samples from DNA- and adenovirus 26 (Ad26)- COVID-19 Spike
protein (S) immunized animals, that will be challenged with COVID-19, will be comprehensively profiled using
Systems Serology, to define the functional humoral immune responses linked to protection from infection/disease
in mice, ferrets, and macaques. Machine learning modeling will be employed to discern key immune response
features that translate usefully across these diverse animal contexts. Coupled to a novel systems-Fc-engineering
approach, the COVID-19 CR3022 monoclonal antibody will be engineered to specifically define the Fc-effector
functions that provide the greatest impact on limiting disease. Collectively, these studies will not only define
correlates of immunity across vaccines and species, but also provide mechanistic insights into the precise
mechanisms by which antibodies may confer protection in the context of future vaccines.

## Key facts

- **NIH application ID:** 10126673
- **Project number:** 3R37AI080289-11S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Galit Alter
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,727
- **Award type:** 3
- **Project period:** 2020-01-09 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126673

## Citation

> US National Institutes of Health, RePORTER application 10126673, Defining humoral correlates of immunity against COVID-19 (3R37AI080289-11S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10126673. Licensed CC0.

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