# Cross-Protective Humoral Immunity to Coronavirus

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $3,169,124

## Abstract

PROJECT 1 SUMMARY
Global establishment of Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is a continued
human threat. While successful vaccine programs are well underway, genetic drift and immune escape have
already begun to subvert immunity. In addition, related zoonotic coronaviruses threaten transition into the
human population. CoVs can be highly transmissible and highly lethal, posing a grave threat to human lives
and world economies. In this light, developing pan-CoV vaccine options in preparation for the expected broad
range of SARS-CoV-2 variants and future emergent coronaviruses could save millions of lives and prevent
future global catastrophes. While current SARS-CoV-2 vaccines targeting the virus spike (S) protein hold great
promise in providing protection against current circulating strains, research is urgently needed to understand
breadth and durability of immunity across the CoV family and to translate this information into next generation
vaccines with increased breadth to cover SARS-CoV-2 escape mutants as well as to address emergent CoVs.
The overall goal of this program is to produce critical information necessary for the design and testing of next
generation CoV vaccine strategies with the greatest possible breadth across the CoV family. The Program
team will identify humoral, cellular, and structural immunologic features influencing clinical outcomes and
immune recognition breadth in human SARS-CoV-2 infection and human vaccination cohorts to fuel design
and pre-clinical testing of protective coronavirus vaccine strategies to identify those with the greatest possible
breadth. Project 1’s goal in this process is to define B cell/serologic properties of broad CoV immunity and
identify vaccine delivery conditions that can best support them. Preliminary discoveries from Project 1 together
with recent literature support the working hypothesis that aspects of vaccine strategy such as antigen choice,
delivery timing, dose, and valency will influence CoV recognition breadth and effectiveness. Knowledge gained
from strategic analysis of the heterogeneity of active human SARS-CoV-2 convalescent and vaccine cohorts
will generate new hypotheses to integrate into pre-clinical vaccine testing approach. In particular, recent work
from Project 1 investigators has identified the conserved S2 domain as promising target for broad CoV
immunity in humans. Program 1’s roles in evaluating these hypotheses are to: 1) identify immune correlates of
convalescent COVID-19 patients and vaccinees that exhibit superior durability and cross-reactivity; 2) define
the mechanisms of cross-reactive monoclonal mediated protection against CoVs in vivo; and 3) evaluate the
efficacy of novel vaccine immunogens to induce protective B cell/functional serological responses in animals.
Supported by Core B, results from Project 1 will provide strategic antibody, serological and memory B cell
analysis in the context of an integrative programmatic approach ...

## Key facts

- **NIH application ID:** 10328119
- **Project number:** 1P01AI165072-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Duane R. Wesemann
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,169,124
- **Award type:** 1
- **Project period:** 2021-09-16 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328119

## Citation

> US National Institutes of Health, RePORTER application 10328119, Cross-Protective Humoral Immunity to Coronavirus (1P01AI165072-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328119. Licensed CC0.

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