# Cross-Kingdom Vaccine Targeting Healthcare-Associated Priority Pathogens Supplement

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2022 · $38,411

## Abstract

Project Summary/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 adhesion/invasion; 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 bioinformatics 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 adhesion to platelets. Hyr1p also shares striking structural homology
with hemagglutinin/hemolysin of MDR Acinetobacter baumannii (AB) and carbapenemase-producing Klebsiella
pneumonia (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 causes of HAIs. Specific aims are: a) optimization of 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 against diverse human
pathogens.

## Key facts

- **NIH application ID:** 10564958
- **Project number:** 3R01AI141202-04S1
- **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:** 2022
- **Award amount:** $38,411
- **Award type:** 3
- **Project period:** 2019-01-09 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10564958

## Citation

> US National Institutes of Health, RePORTER application 10564958, Cross-Kingdom Vaccine Targeting Healthcare-Associated Priority Pathogens Supplement (3R01AI141202-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10564958. Licensed CC0.

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