# Cross-Kingdom Vaccine Targeting Healthcare-Associated Priority Pathogens

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2023 · $1,151,780

## Abstract

This application describes development of a broad-spectrum vaccine targeting multidrug resistant (MDR)
organisms, principally related to healthcare-associated infections (HAIs). Our premise is that an effective way to
prevent antimicrobial resistance is through vaccines rather than continued introduction of new drugs.
Our development program is based on two cell wall antigens of the fungus Candida albicans: Als3p, a multi-
function adhesin/invasin; and Hyr1p, which enables C. albicans to evade phagocyte killing. Vaccination of mice
with either antigen provides significant protection against disseminated infections caused by Candida species
and vulvovaginal candidiasis (VVC) due to C. albicans. Importantly, vaccination with both antigens synergistically
protect mice from VVC.
Using innovative computational molecular modeling and bioinformatic strategies, we identified highly significant three
dimensional (3-D) structural and functional homology between Als3p, and methicillin resistant Staphylococcus
aureus (MRSA) surface adhesive molecules, including clumping factor A. Similarly, Hyr1p, shares 3-D structural
homology to MRSA SraP, an adhesin to platelets. Hyr1p also shares striking structural homology with
hemagglutinin/hemolysin of MDR Acinetobacter baumannii (AB) and carbapenemase-producing Klebsiella
pneumoniae (CPKP). Active immunization with the recombinant N terminus of Als3p (rAls3p-N) results in >50%
survival in an otherwise fatal murine model of staphylococcemia and protects mice from Skin and Skin Structure
Infection due to MRSA. Similarly, active or passive immunization (with a monoclonal antibody) targeting the
recombinant N-terminus of Hyr1p protects mice from MDR AB, and CPKP infections. Thus, our vision is to develop
a “cross-kingdom” dual antigen vaccine targeting Candida, MRSA, and MDR AB and CPKP. All are important leading
cause of HAIs. Specific aims are: a) optimization of the dual rAlsp3-N/rHyr1p-N vaccine by synergy evaluation, fine-
tuning of antigen dose, and use of clinically-safe newer adjuvants; b) conduct GLP-enabling studies including analytical
assay development/optimization, formulation scale up of an optimized dual antigen vaccine and stability studies; and c)
evaluate the final vaccine formulation for activity with and without antibiotics and perform an IND-enabling GLP-toxicity
study of the optimized final vaccine formulation.
In collaboration with NovaDigm Therapeutics, we advanced the development of rAls3p-N formulated with
aluminum hydroxide (i.e. NDV-3A) from the academic laboratory to a phase 1b/2a trial showing efficacy of the
vaccine in protecting women <40 years old from recurrent VVC. Thus, this proposal will leverage our combined
strengths in basic discovery and product development of convergent vaccine antigens protecting against diverse
human pathogens.

## Key facts

- **NIH application ID:** 10535474
- **Project number:** 5R01AI141202-05
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **Principal Investigator:** ASHRAF S. IBRAHIM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,151,780
- **Award type:** 5
- **Project period:** 2019-01-09 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535474

## Citation

> US National Institutes of Health, RePORTER application 10535474, Cross-Kingdom Vaccine Targeting Healthcare-Associated Priority Pathogens (5R01AI141202-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10535474. Licensed CC0.

---

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