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Protective antibody in streptococcal infection models

Award Number: R01AI173565
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: 12/02/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Protective antibody in streptococcal infection models - ABSTRACT The initial contact between newly transmitted group A streptococci (GAS) and its human host can be readily thwarted by antibody (Ab) directed to the appropriate GAS antigens (Ags). To best simulate this microenvironment, physiological (i.e., low) inoculum doses of GAS are essential. The goal of this proposal is to identify Ags, alone and in combinations representing multicomponent vaccines, that are the most effective targets of Ab-mediated immunity and collectively can provide worldwide coverage against all GAS strains. The underlying rationale for the proposed approach rests on two principles: That serum obtained from children just prior to a new GAS infection lacks protective Ab, and that serum obtained from most adults has at least low levels of persisting protective Ab. The latter is based on the very low incidence of GAS infection in adults, likely the result of protective immunity that developed following repeated infections earlier in life. Hypotheses on protective Ag-specific Ab generated from analysis of pediatric serum (aim 1) are experimentally tested in mice (aim 2). Pre-infection pediatric serum is analyzed for lack of protective Ab to leading vaccine candidates. Adult serum is used as a source for purified immunoglobulin (Ig) specific to the vaccine target Ags missing in susceptible children. Immunodeficient mice are passively immunized with the Ag-specific Ig purified from adults and challenged with low infective doses of GAS. The Ag-specific Ig that confers protection in mice equates to a human serum-based correlate of protection (CoP). Four major forms of GAS disease are modeled in mice and evaluated for protective immunity: upper respiratory tract infection, impetigo, skin and soft tissue infection and invasive disease. GAS from all three major subpopulations of strains are tested: throat specialists, skin specialists and generalists. The Ag targets evaluated are leading vaccine candidates and include broadly and semi-conserved Ags as well as surface and secreted Ags. If successful, this work will identify a collection of Ag targets that can serve as the basis for global protection. It will also deliver two new standardized platforms – screening of pre-infection human serum Ab to GAS Ags and improved mouse models - for future identification and straightforward comparison of additional GAS vaccine candidates.


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: 2025 ( Subtotal = $0 )
2025	2024	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Allergy and Infectious Diseases Research	000	2	12/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $599,556 )
2024	2024	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Allergy and Infectious Diseases Research	000	2	12/11/2023	NON-COMPETING CONTINUATION	$539,601
2024	2024	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Allergy and Infectious Diseases Research	001	2	5/14/2024	NON-COMPETING CONTINUATION	$59,955
														Subtotal = $599,556

Issue Date FY: 2023 ( Subtotal = $593,872 )
2023	2023	NEW YORK MEDICAL COLLEGE	40 SUNSHINE COTTAGE RD	VALHALLA	NY	10595	WESTCHESTER	USA	Allergy and Infectious Diseases Research	000	1	12/2/2022	NEW	$593,872
														Subtotal = $593,872

Grand Total All Awards = $1,193,428

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Protective antibody in streptococcal infection models

Award Number: R01AI173565

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: 12/02/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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