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Characterization of pan-fungal monoclonal antibodies targeting Aspergillus

Award Number: R21AI202073
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/17/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Characterization of pan-fungal monoclonal antibodies targeting Aspergillus - The fungal pathogen Aspergillus poses a significant health threat to individuals with weakened immune systems, pre-existing lung disease, and pulmonary co-infections, causing an estimated 2.1 million cases of life-threatening invasive aspergillosis (IA) annually, and approximately 1.8 million deaths (85% mortality). Recent estimates indicate that the frequency of IA has dramatically risen both domestically and globally in recent decades. Even with medical treatment, IA has a disproportionally high rate of morbidity, mortality, and health care cost per incidence of disease. Current treatment and prophylactic strategies for IA rely heavily on a limited number of antibiotics that are even further hindered by drug-drug interactions, low or variable exposure, toxicity, and increasing drug resistance. Despite the increasing burden of IA and other Aspergillus-associated diseases, there are currently no clinically approved fungal vaccines or alternatives to antibiotics that can work in concert with preexisting treatment options for treatment and prevention. Our long-term goal is to address the critical need for new therapeutic and prophylactic strategies that will reduce Aspergillus-associated morbidity and mortality. Antifungal monoclonal antibodies (mAb) have the potential to serve as prophylactic, priority, or adjunctive therapies for IA and other Aspergillus-associated diseases. Based on preliminary data demonstrating that 1) immunization with NXT-2 is protective against multiple fungal pathogens Aspergillus in an immunosuppressed murine model of IA, 2) Anti-NXT-2 polyclonal antibodies (NXT-2 pAbs) bind to the surface of Aspergillus and enhance opsonophagocytic killing (OPK), and 3) passive transfer of NXT-2 pAbs is protective against IA in vivo, we have generated a panel of anti-NXT-2 mAbs (NXT-2 mAbs) to investigate their antifungal potential. Our overall objective is to characterize the binding properties and define the mechanisms of action of antifungal mAbs with the highest therapeutic potential for Aspergillus-associated disease management. Our working hypothesis is that mAbs targeting the antifungal epitopes of NXT-2 and bind the cell surface of Aspergillus will promote immunologic control, and that antifungal activity will correlate with the mAb strength of binding to NXT-2. In aim 1 we will determine the epitope specificity and binding characteristics of NXT-2 mAbs. In aim 2 we will evaluate the anti- Aspergillus activity of NXT-2 mAbs in vitro. Functional assays will be performed to 1) define the antifungal epitopes of NXT-2, 2) down select mAbs with the highest anti-Aspergillus activity and characterize their mechanisms of action, and 3) evaluate top mAbs for additive or synergistic activity. The expected outcomes will advance our understanding of the role of antibodies in the control of Aspergillus. mAb with the best antifungal activity and combinations with the highest additive or synergistic activity will be advanced for future evaluation in vivo. This work will have a significant impact by providing proof-of-principle results for further antifungal mAb development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $228,000 )
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	8/17/2026	NEW	$228,000
														Subtotal = $228,000

Grand Total All Awards = $228,000

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Characterization of pan-fungal monoclonal antibodies targeting Aspergillus

Award Number: R21AI202073

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/17/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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