# Population genotyping of the germline immunoglobulin repertoire in AIDS-designated rhesus macaque breeding colonies

> **NIH NIH R24** · EMORY UNIVERSITY · 2022 · $859,777

## Abstract

PROJECT SUMMARY
A strategic priority for contemporary HIV vaccine research is the development of approaches to elicit broadly
neutralizing antibodies (bNAbs) able to neutralize diverse strains of the virus. A cornerstone of bNAb discovery
is the ability to conduct accurate, longitudinal studies of antibody evolution in HIV infected individual as they gain
mutations and acquire neutralization activity. Currently, it is not possible to perform analogous antibody evolution
tracing studies using rhesus macaques (RMs), due to a lack of defined immunoglobulin (IG) alleles. This is best
exemplified by a recent study large scale vaccine study by our group in which we sequenced a de novo genome
of a RM using long-read sequencing in order to obtain accurate assemblies of the IG loci. This reference
significantly enhanced the accuracy of tracking the mutations from germline elicited by our vaccine strategies.
This tool was critical in deciphering trajectories that led to either autologous neutralization or immunodominance
and non-neutralizing responses. In other work, we have developed novel bioinformatics methodology (germline
inference) to identify the unmutated germline antibody sequence from immunoglobulin repertoire. This work has
led to identification of hundreds of novel inferred IG alleles.
The goal of this R24 proposal is to build on these findings by characterizing the IG alleles and haplotypes
in AIDS designated RMs at NHP primate centers that serve the major HIV vaccine stakeholders. Currently,
the IG loci are poorly characterized in RMs, in part due to technical challenges. IG genotypes are not currently
used as criteria when enrolling RMs into vaccine studies. In contrast, MHC genotyping of RMs has become
standard practice for vaccine studies and is a core function in genetic management of NPRC RM colonies. The
lack of genetic data on the RM IG loci is therefore a significant knowledge gap and impairs our ability to assess
the evolution of antibodies in monkeys administered vaccines that aim to elicit neutralizing antibodies. The goal
of this R24 proposal is to address this strategic need and build a resource in which this genetic information (IG
allele sequence information, haplotype, and allele usage) is available to the HIV vaccine and NHP research
communities.

## Key facts

- **NIH application ID:** 10400149
- **Project number:** 5R24AI162317-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Steven Edward Bosinger
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $859,777
- **Award type:** 5
- **Project period:** 2021-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400149

## Citation

> US National Institutes of Health, RePORTER application 10400149, Population genotyping of the germline immunoglobulin repertoire in AIDS-designated rhesus macaque breeding colonies (5R24AI162317-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10400149. Licensed CC0.

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