# Starve and Kill: Engineered Antigens Targeting Nutrient Acquisition Pathways Essential for Gonococcal Infection and Disease

> **NIH NIH U19** · GEORGIA STATE UNIVERSITY · 2020 · $1,819,769

## Abstract

Abstract/Summary
Neisseria gonorrhoeae has re-emerged as a global public health concern as it causes roughly 100 million new
infections each year and isolates have emerged that are resistant to all clinically-relevant antibiotics; these
alarming trends have prompted the US Center for Disease Control to name N. gonorrhoeae as one of three
`urgent' microbial threats. The success of N. gonorrhoeae is attributable in part to its capacity to colonize the
female genital tract without obvious clinical manifestation, allowing it to persist undetected as it is spread to
sexual partners. Consistent with this, N. gonorrhoeae does not express factors with overt virulent potential.
Instead, it exhibits a lifestyle intent on avoiding and actively subverting immune detection, and expresses elegant
systems to access highly restricted nutrient stores to support its growth within human tissues. This translational
research program will exploit our recent success in targeting the receptor proteins that allow N. gonorrhoeae to
acquire iron and zinc during infection; these trace metals are essential for life but effectively absent in mammalian
tissues due to a process known as `nutritional immunity'. We have unexpectedly discovered that the bacterial
surface-exposed receptor proteins that bind the host iron sequestering-serum protein transferrin does not elicit
a protective immune response because it rapidly binds transferrin in the tissues, and that we can overcome this
deficit by generating a point mutant that is structurally identical except that it does not bind transferrin. We will
use this approach to generate immunogens that target alternative iron and zinc acquisition systems of N.
gonorrhoeae, and then produce a multicomponent vaccine that elicits an immune response that will
simultaneously starve the bacteria of these two essential nutrients and kill the bacteria through classical
antibody-dependent activities. Along with this directly translational pursuit, we will also perform community
outreach studies to understand the potential resistance to gonococcal vaccines among different stakeholder
populations and reveal potential strategies to overcome these barriers. Then, our genomic and phenotypic
analysis of the global diversity of the receptor systems that we are targeting will be integrated with global
gonococcal epidemiology data and the understanding gained through our community-based studies to make
informed predictions about the potential impact of different vaccine formulation and public health-focused
implementation strategies on the global prevalence of N. gonorrhoeae. When complete, this program will
therefore deliver a vaccine formulation that targets distinct but equally essential nutrient uptake pathways to
confer sterilizing immunity against gonococcal infection and will provide actionable information that will guide the
eventual implementation of this vaccine in a manner that will ultimately allow eradication of this devastating
human-restrict...

## Key facts

- **NIH application ID:** 9899916
- **Project number:** 5U19AI144182-02
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** CYNTHIA N CORNELISSEN
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,819,769
- **Award type:** 5
- **Project period:** 2019-03-25 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899916

## Citation

> US National Institutes of Health, RePORTER application 9899916, Starve and Kill: Engineered Antigens Targeting Nutrient Acquisition Pathways Essential for Gonococcal Infection and Disease (5U19AI144182-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899916. Licensed CC0.

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