# SARS-CoV-2 vaccines based on RBDs with engineered glycosylation sites

> **NIH NIH R44** · EMMUNE, INC · 2022 · $300,000

## Abstract

ABSTRACT
 We are developing vaccine antigens for SARS-CoV-2 that focus the antibody response onto neutralizing
epitopes in the receptor binding domain (RBD) of the viral Spike (S) protein. Efficient expression of the RBD
in technically-demanding formats, e.g., on a self-assembling multimer scaffold, was achieved by engineering
N-linked glycosylation sites into the RBD. The engineered N-linked glycosylation sites occlude hydrophobic
patches that form inter-subunit interfaces in the native S protein, but that interfere with expression of the RBD
in other contexts. The glycans also help to focus the immune response away from off-target faces of the
RBD, and onto the targets for potent neutralizing antibody responses. We will extend the potential for this
strategy to focus the neutralizing antibody response further, onto conserved epitopes in the RBD. This overall
strategy maximizes the focusing of neutralizing antibody responses onto epitopes that are conserved among
variants of SARS-CoV-2. In addition, we will compare, and possibly combine, immunofocusing with
approaches designed to elicit variant-specific neutralizing antibodies. We will develop and utilize two distinct
platforms for expressing these RBD antigens: mRNA delivered by lipid nanoparticles (LNPs), and a novel
scaffold for efficiently displaying multimers of RBD antigens as recombinant protein. LNP-mRNA vaccines
have the advantage of being a validated approach for vaccinating against SARS-CoV-2, whereas the novel
multimer scaffold has the advantage of being heat stable after lyophilization. The antigens generated by this
project exploit three layers of immunofocusing to elicit or boost antibody responses that neutralize diverse
variants of SARS-CoV-2.

## Key facts

- **NIH application ID:** 10484882
- **Project number:** 1R44AI170392-01
- **Recipient organization:** EMMUNE, INC
- **Principal Investigator:** MICHAEL DAVID ALPERT
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2022-08-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484882

## Citation

> US National Institutes of Health, RePORTER application 10484882, SARS-CoV-2 vaccines based on RBDs with engineered glycosylation sites (1R44AI170392-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10484882. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*