# Assessing HIV-1 Broadly Neutralizing Antibody Association Pathways for Vaccine Immunogen Design

> **NIH NIH DP2** · DUKE UNIVERSITY · 2022 · $476,900

## Abstract

ABSTRACT
Macromolecular interactions are often understood from the perspective of the bound state as
determined at high-resolution from x-ray crystallography or cryo-electron microscopy with kinetic
and thermodynamic parameters used to describe the interaction process. This approach is,
however, limited spatially and temporally to a bulk, population level description of the process
from the perspective of affinity and kinetics, and the single state perspective of a bound state
structure. The process of forming an interaction is, in fact, quite complex, involving random
collisions between molecules that transition through a complicated set of pathways to the final
bound state. These collisions and the mechanism by which they achieve the bound state
determine the association rate but are not well defined by current methods. Here, a combined
computational and experimental approach to the interrogation of the process of antibody-
antigen binding in HIV-1 N332-glycan targeting broadly neutralizing antibodies is proposed to
enable precise enhancement of antibody-immunogen association rate kinetics. Using molecular
simulation, full encounter to bound state transition mechanisms will be elucidated at atomic
resolution. The goal of this effort is to enable precise selection of antigens with an affinity
gradient conducive to the consistent induction of broadly neutralizing antibody responses via
vaccination. The definition of design principles by which the kinetics of an interaction may be
manipulated in a protein engineering context will have a broad impact on the design of novel
therapeutics and macromolecular probes in any biological context.

## Key facts

- **NIH application ID:** 10458681
- **Project number:** 5DP2AI164323-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Rory Henderson
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $476,900
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458681

## Citation

> US National Institutes of Health, RePORTER application 10458681, Assessing HIV-1 Broadly Neutralizing Antibody Association Pathways for Vaccine Immunogen Design (5DP2AI164323-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458681. Licensed CC0.

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