# Eliciting tyrosine-sulfated neutralizing antibodies recognizing the Env apex

> **NIH NIH R21** · SCRIPPS FLORIDA · 2021 · $277,500

## Abstract

PROJECT SUMMARY
An effective HIV-1 remains an important but elusive goal. One promising approach to such a vaccine
uses sequential immunization to guide B-cell receptor (BCR) maturation. To do so, one first amplifies
immature unmutated precursors of a particular class of broadly neutralizing antibodies (bNAbs). These
precursor BCR are then shepherded to recognize HIV-1 envelope glycoprotein (Env) using increasingly
native Env antigens. Sequential immunization strategies for both VRC01- and V3-glycan-classes of
bNAbs are being developed. Here we establish the foundations for using the same general strategy to
elicit V2-glycan/apex antibodies. Apex bNAbs have properties that both complicate such an approach
but ultimately make success more likely. Specifically these bNAbs bind Env largely through their long,
acidic and tyrosine-sulfated heavy-chain CDR3 region. Thus there is less need for extensive somatic
hypermutaion characteristic of V3-glycan and VRC01-class bNAbs. However, apart from their long
sulfated CDR3 regions, apex bNAbs have few distinguishing features. Here we show that we can elicit
antibodies in rats with long tyrosine-sulfated CDR3 regions using anti-sulfotyrosine antibodies as
antigens. We propose to optimize this approach and use it in concert with oligomeric forms of Env trimers
to elicit anti-apex antibodies. These studies will develop a potentially easier approach to generating
broad and potent anti-HIV-1 antisera.

## Key facts

- **NIH application ID:** 10122907
- **Project number:** 5R21AI152836-02
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Michael R. Farzan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $277,500
- **Award type:** 5
- **Project period:** 2020-03-06 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122907

## Citation

> US National Institutes of Health, RePORTER application 10122907, Eliciting tyrosine-sulfated neutralizing antibodies recognizing the Env apex (5R21AI152836-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10122907. Licensed CC0.

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