# Antibody Durability Dynamics

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $686,383

## Abstract

Project Summary
Antibodies specific for pathogenic threats can provide immediate protection from infectious disease but
longevity of an antibody responses after vaccination or infection can be highly variable. Responses induced by
some live vaccines can persist for a lifetime, whereas protein-based vaccines are in general shorter lasting.
However, antibody durability is not necessarily linked to the use of live virus as long-lived antibody responses
have been shown to be induced by the human papilloma virus (HPV) vaccine, a non-live viral-like particle-
based platform. This suggests that distinct immunological cues can be engineered to result in the generation of
longer-lived antibody responses. While memory lymphocytes also provide a system of protective efficacy,
strategies to maximize robust levels of protective secreted antibodies that are stable over time is an important
goal in modern immunology. Understanding the capabilities of the immune system in this context, and how
available vaccines can elicit durable secreted antibody responses will be important to decipher. This is relevant
to the ongoing SARS-CoV-2 pandemic and for vaccine strategies more broadly. Preliminary data suggest that
antibodies induced by natural infection harbor robust long-term stability at modest levels and greater polyclonal
neutralizing breadth across viral variants compared to infection-naïve vaccinees. In addition, differential
antibody durability trajectories tend to favor COVID-19 convalescent subjects with dual memory B cell features
of greater antibody somatic mutation and cross-coronavirus reactivity. These findings support a hypothesis that
high somatical mutation and cross-reactivity in antigen-binding memory B cell repertoires early after recovery
predicts antibody durability and that recalled immunity may confer greater longevity of differentiated plasma
cells. This hypothesis will be examined in two aims, (i) to illuminate factors influencing anti-SARS-CoV-2
antibody durability, and (ii) to chart the functional evolution of anti-CoV memory B cell over time. For aim 1,
human and mouse studies will be used to illuminate potential mechanistic insights and features connected to
durable antibody responses. For aim 2, the durability and evolution of memory B cell repertoire antigen
recognition capacity will be charted over time to assess the evolving relationship between secreted polyclonal
and memory B cell repertoires. This work is expected to shed light on factors that influence longevity and
evolution of antibody responses, which will be important for ongoing improvement of vaccine strategies.

## Key facts

- **NIH application ID:** 10501415
- **Project number:** 1R01AI170715-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Duane R. Wesemann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $686,383
- **Award type:** 1
- **Project period:** 2022-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501415

## Citation

> US National Institutes of Health, RePORTER application 10501415, Antibody Durability Dynamics (1R01AI170715-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10501415. Licensed CC0.

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