# Project 2: Using gonococcal lactoferrin-binding proteins as vaccine antigens

> **NIH NIH U19** · GEORGIA STATE UNIVERSITY · 2020 · $286,159

## Abstract

Contact PD/PI: Cornelissen, Cynthia
Summary: Project 2 - Targeting lactoferrin receptors for a gonococcal vaccine
This goal of this project is to develop a broadly cross-protective vaccine against Neisseria gonorrhoeae, the
bacteria responsible for the common sexually-transmitted disease, gonorrhea. The emergence of strains of N.
gonorrhoeae that are resistant to most antibiotics has raised the specter of untreatable gonorrhea, adding
urgency for the development and implementation of effective vaccines for prevention of this infection and its
sequelae. N. gonorrhoeae is human-specific pathogen that exclusively resides in genitourinary tract, or less
frequently, in the upper respiratory tract, of its human host. Our approach is to target the surface components
responsible for mediating iron acquisition from the host iron binding proteins, transferrin (Tf) and lactoferrin (Lf),
since these two systems have been shown to be essential for survival of the bacteria and their ability to cause
infection in a human male urethral infection model. Since the bacteria cannot survive without these receptor
proteins, they will not be able to escape vaccine coverage by loss of the receptors, thus could be eliminated
from vaccinated individuals if we are successful in developing a fully cross-protective vaccine against all
variants of the receptor proteins.
This project is focused on using structure-guided antigen design to generate engineered antigens targeting
both the surface lipoprotein, lactoferrin binding protein B (LbpB), and the integral outer membrane transport
protein, lactoferrin binding protein A (LbpA), that will collectively induce a broadly cross-protective immune
response against all known variants of these proteins. Our novel integrated vaccine design and evaluation
pipeline approach will use libraries of antigenic variants in immunoassays and strain libraries in colonization
and infection models to evaluate the cross-reactive and cross protective properties of the immune response to
guide the selection of combinations of antigens. We will determine the global sequence diversity of the target
antigens (LbpB and LbpA) and then develop non-binding mutants of representative variant LbpBs that are
predicted to collectively provide a broad cross-protective immune response against all LbpB variants. We will
evaluate the immunological properties of the negatively charged regions in the C-lobe of LbpB, determine the
impact of their removal and determine the optimum combination of LbpA epitopes that can be displayed on the
LbpB C-lobe that induces a broadly cross-protective response against LbpA.
The final step will be to integrate the results from an established NIH grant focused on developing antigens
targeting transferrin binding protein B and A (TbpB and TbpA) and determine the optimum combination of
engineered TbpB and LbpB antigens displaying epitopes from TbpA and LbpA to induce a broadly cross-
protective immune response against all four antigens....

## Key facts

- **NIH application ID:** 9899930
- **Project number:** 5U19AI144182-02
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Anthony Bernard Schryvers
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $286,159
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899930

## Citation

> US National Institutes of Health, RePORTER application 9899930, Project 2: Using gonococcal lactoferrin-binding proteins as vaccine antigens (5U19AI144182-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9899930. Licensed CC0.

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