IMMUNETHEP, S.A.

CANTANHEDE

Unclaimed

Subcontracting experience

1 record from government sources. Past participation is not evidence of current teaming interest.

Role	Agency	Description	Vehicle	Obligated	Action date	Period
Subcontractor	Department of Health and Human Services	THE GOAL OF THIS PROJECT IS TO COMPLETE PHASE 1 CLINICAL TRIALS WITH A NEW VACCINE FORMULATION THAT PREVENTS INVASIVE DISEASE CAUSED BY ESCHERICHIA COLI. DIFFERENT PATHOGENIC BACTERIA, INCLUDING E. COLI, POSSESS AN EXTRACELLULAR FORM OF GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPDH) THAT HAS A POTENT IMMUNOSUPPRESSIVE ACTIVITY IN THE MAMMALIAN HOSTS. HOST IMMUNOSUPPRESSION IS MEDIATED BY THE ABILITY OF GAPDH TO BIND TO TLR2 AND TO TRIGGER A FAST PRODUCTION OF INTERLEUKIN-10. EXCRETION OF BACTERIAL GAPDH THROUGHOUT THE BLOOD STREAM OF THE HOST OCCURS IMMEDIATELY AFTER INFECTION AND INHIBITS EARLY EVENTS OF THE INFLAMMATORY RESPONSE, ALLOWING THE BACTERIA TO SPREAD SYSTEMICALLY WITHIN FEW HOURS. NEUTRALIZATION OF BACTERIAL GAPDH IS ESSENTIAL TO PROMOTE A PROTECTIVE RESPONSE AGAINST E. COLI INFECTIONS. ACKNOWLEDGING THE IMPORTANCE OF EXTRACELLULAR GAPDH IN THE PATHOGENICITY OF E.COLI CAN EXPLAIN WHY OTHER ATTEMPTS TO DEVELOP VACCINES THAT TARGET ONLY STRUCTURAL EPITOPES HAVE FAILED. AS IT IS WIDELY KNOWN, GAPDH IS AN UBIQUITOUS ENZYME THAT, IN ITS INTRACELLULAR FORM IS ESSENTIAL FOR GLYCOLYSIS. HOWEVER, E. COLI POSSESS TWO DIFFERENT GENES THAT CODE FOR TWO DIFFERENT GAPDH: I) THE INTRACELLULAR GLYCOLYTIC ENZYME CODED BY GAPA GENE AND II) THE EXTRACELLULAR VIRULENCE FACTOR CODED BY GAPC GENE. THE ABROGATION OF GAPC GENE DOES NOT INFLUENCE THE METABOLIC RATE OF THE BACTERIA BUT REDUCES DRAMATICALLY THE ABILITY OF BACTERIA TO CAUSE DISEASE. HUMANS DO NOT POSSESS GAPC-ENCODED GAPDH, BUT THERE IS STILL A SIGNIFICANT DEGREE OF IDENTITY BETWEEN GAPC- AND GAPA-ENCODED GAPDH (APPROX. 50%). TO OVERCOME ANY REACTIVITY TO HUMAN GAPDH, WE IDENTIFIED REGIONS (PEPTIDES) EXPOSED TO SOLVENT ON BACTERIAL GAPDH THAT ARE COMPLETELY ABSENT FROM HUMAN GAPDH. WITHIN THIS PROJECT WE INTEND TO DEVELOP AN IMMUNOGENIC FORMULATION THAT TARGETS THE IDENTIFIED REGIONS. DIFFERENT FORMULATIONS WILL BE TESTED FOR THEIR IMMUNOGENICITY AND ABILITY TO PREVENT INVASIVE DISEASE CAUSED BY E. COLI IN IN VIVO CHALLENGING ASSAYS IN THE MOUSE MODEL. THE BEST COMBINATION OF POLYPEPTIDE + CARRIER PROTEIN WILL PROCEED TO PRECLINICAL STUDIES AND PHASE 1 STUDIES. KC3975 Parent award context Parent award agency: Department of Health and Human Services · Office of Assistant Secretary for Preparedness and Response Parent award NAICS: 541714 Parent award performance state: MA Parent award description: CARB-X GLOBAL ANTIBACTERIAL ACCELERATOR OTA View parent award on USAspending	—	$65,188	Dec 20, 2024	— – —

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