# Integrating innate and adaptive pathways in vaccine responses

> **NIH NIH U19** · ROCKEFELLER UNIVERSITY · 2021 · $2,087,668

## Abstract

ABSTRACT – Overall
Significant progress in basic immunology research over the last three decades has resulted in numerous medical
advances and dissected the general mechanisms by which the human immune system responds to foreign
antigens. However, a much more substantial understanding of the coordinated molecular mechanisms involved
in eliciting immunity will be required, as each viral pathogen poses unique challenges to the immune system and
the elicited immune responses are characterized by substantial heterogeneity that impacts disease susceptibility
and pathogenesis. Indeed, it is expected that B-cell responses against diverse viral pathogens are uniquely
evolved during infection to shape the functional activity of IgG antibodies. Studies from viral infectious diseases
have shown that antiviral IgG antibodies have the capacity to mediate a wide spectrum of opposing functions: (i)
protective functions, including neutralization, viral opsonization, and clearance of infected cells and (ii)
pathogenic activities, which enhance viral infectivity, disease susceptibility and severity; a phenomenon termed
as antibody-mediated enhancement (ADE) of disease. ADE mechanisms have been previously suggested to
account for susceptibility to dengue disease, as epidemiological data support that prior flavivirus infection is the
major risk factor for dengue disease, implicating the presence of cross-reactive, non-neutralizing IgG antibodies
to this process. Understanding the heterogeneity of IgG responses elicited upon infection or vaccination with
diverse viral antigens is therefore critical for characterizing the immunological mechanisms that drive human
immunity and determine the protective vs. pathogenic activity of IgG antibodies. Our Center will feature three
Projects directed by Drs. Ravetch (Project 1: Fc domain effector activity in dengue disease), Nussenzweig and
Rice (Project 2: Understanding B cell memory in response to diverse virus infections), and Wang (Project 3:
Immunity to dengue viruses), supported by a scientific core (Core A: Transgenic mouse core) and the
administrative core (Core B). Through a series of collaborative studies between the three Projects, our Center
aims to study human antiviral immune responses during infection and vaccination and characterize the immune
mechanisms that regulate the function of IgG antibodies in humans. More specifically, we aim to characterize
the heterogeneity of IgG responses elicited upon vaccination or infection with diverse viral pathogens, including
HBV and flaviviruses, like Zika and dengue. Additionally, we will dissect the ADE mechanisms by which IgG
antibodies mediate disease-enhancing activities and contribute to dengue disease susceptibility and
pathogenesis. These studies will provide novel insights into the mechanisms that drive protective immunity and
modulate antibody function, having a broader impact on the development of vaccination strategies against
infectious pathogens.

## Key facts

- **NIH application ID:** 10134201
- **Project number:** 5U19AI111825-08
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** JEFFREY Victor RAVETCH
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,087,668
- **Award type:** 5
- **Project period:** 2014-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134201

## Citation

> US National Institutes of Health, RePORTER application 10134201, Integrating innate and adaptive pathways in vaccine responses (5U19AI111825-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134201. Licensed CC0.

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