Multivalent Adjuvant Immunization to Prevent Hospital Acquired Infections

PROJECT SUMMARY/ABSTRACT
Two million Healthcare Associated Infections (HAIs) occur per year in the US, killing andgt;90,000 patients and
costing ~$50-100 billion (adjusted by CPI to 2020 dollars). HAIs are the 6th leading cause of death in the US,
ahead of diabetes and kidney disease. Reducing HAIs is a top priority of the US Department of Health and
Human Services1 and experts have called for novel strategies including vaccination to achieve this goal.2ExBaq is a biotechnology company founded by a consortium of scientists and business colleagues who
have spent years studying antibiotic-resistant nosocomial pathogens. ExBaq is developing a vaccine to
prevent HAIs comprised of innate-immune stimulatory molecules that provide broad-spectrum protection
against infection caused by cross-kingdom HAI pathogens (preliminary data). Our vaccine consists of:A) Aluminum hydroxide (Al(OH)3), which is contained in multiple FDA-approved vaccines, andenhances immunity via multiple mechanisms, including induction of depot formation, activating theNALP3 inflammasome, and enhancing particulate uptake by macrophages;B) Monophosphoryl Lipid A (MPL), which is also contained (in combination with Al(OH)3) in multipleFDA-approved vaccines and activates the NF-κB pathway via TLR4 ligation;C) Mannan, which stimulates a variety of innate and adaptive immune pathways, and was safe inclinical trials when administered parenterally.During Phase I we have confirmed that this triple adjuvant regimen has the broadest protection against
pathogens, affording lower doses (important for cost of goods), compared to a triple regimen containing whole
glucan particles instead of mannan, or with a quadruple regimen (preliminary data). Efficacy of the triple
regimen has been confirmed in lethal mouse models of carbapenem-resistant Acinetobacter baumannii and
Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and disseminated infection
caused by the fungi Candida albicans and Rhizopus delamar (mucormycosis). Given efficacy against Gram-
positive and -negative bacteria and fungal pathogens, our trivalent vaccine has potential to prevent
HAIs caused by the highest priority, antibiotic-resistant nosocomial pathogens. Having established an
optimal lead composition in Phase I, the goal of Phase II is to establish GMP, conduct pre-clinical immuno-
toxicology studies, and to complete key steps to supporting IND submission. Our Aims are to:
AIM 1: Establish GMP manufacturing for our vaccine regimen.
AIM 2: To complete pre-clinical immuno-toxicity studies to support an IND application.
AIM 3: Complete key steps to support IND-filing at end of funding.New technologies are needed to prevent, hospital acquired infections, which are the 6th leading
cause of death in the US. The purpose of this proposal is to establish proof of principle that a
novel vaccine strategy can broadly prevent infections caused by the most dangerous and
common bacterial and fungal pathogens found in hospitals.