Thursday, December 26, 2024 12/26/2024

Assays for acceleration: from fit-for-purpose models to scalable assays of broad systemic and mucosal protection against all strains of Group A Streptococcus

Award Number: R01AI173567
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT There is renewed international momentum to develop vaccines to prevent infections caused by the highly adapted, human-restricted bacterial pathogen Group A Streptococcus (GAS). However, the lack of a known correlate of human immune protection against GAS infection and the limitations of current in vitro assays and preclinical models have impeded development of promising preclinical vaccine candidates and threatens future investment in GAS vaccine discovery and design. To overcome this roadblock, we will undertake a cross- disciplinary collaborative research program, drawing on highly relevant human samples and developing a new human ex vivo tissue model, to discover broadly applicable potential human correlates of protection that will inform design of practical immunoassays fit for deployment in clinical vaccine trials. Rather than adhering to the constraints of historical GAS immunoassays, we are explicitly targeting preferred characteristics for clinical immunogenicity assays to support vaccine development, such as practicality, accuracy and broad application to relevant syndromes and strains. GAS naturally infects humans only, therefore we will take a human-centred approach, purposefully moving away from animal models that do not adequately represent relevant complexities of the human immune response. We will apply cutting edge immunology approaches to study diverse human samples from parallel research programs, including from externally funded trials using our own GAS human challenge model to evaluate vaccine protection against pharyngitis, the primary target indication for vaccine development efforts. Initial published findings from the GAS pharyngitis human challenge model show that protection may be associated with robust early mucosal and systemic Th1 inflammatory responses, in clear alignment with recent preclinical animal model findings, and highlighting vaccine-induced antigen-specific Th1 responses as a correlate of protection for multicomponent vaccines. We will characterize the transcriptomic basis for this immune response using our existing human sample collection. We will draw on our experience with human whole blood stimulation assays and tissue models to establish whole-blood and organotypic tonsil tissue models as our primary research tools. This approach will allow us to interrogate ex vivo human immune responses to whole bacteria, culture supernatant, and vaccine antigens to discover potential systemic and mucosal correlates of protection. These broad-ranging efforts to identify immune pathways implicated in vaccine-induced protection will inform the design of a practical, scalable, and strain-agnostic whole-blood in-tube assay (analogous to cytokine release assays), and a high-throughput functional oral fluid mucosal assay to test in forthcoming clinical trials of novel GAS vaccines.


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 = $486,137 )
2025	2025	MURDOCH CHILDREN'S RESEARCH INSTITUTE	ROYAL CHILDREN'S HOSPITAL FLEMINGTON RD	PARKVILLE				AUS	Allergy and Infectious Diseases Research	000	3	12/20/2024	NON-COMPETING CONTINUATION	$486,137
														Subtotal = $486,137

Issue Date FY: 2024 ( Subtotal = $486,469 )
2024	2024	MURDOCH CHILDREN'S RESEARCH INSTITUTE	ROYAL CHILDREN'S HOSPITAL FLEMINGTON RD	PARKVILLE				AUS	Allergy and Infectious Diseases Research	000	2	11/29/2023	NON-COMPETING CONTINUATION	$437,822
2024	2024	MURDOCH CHILDREN'S RESEARCH INSTITUTE	ROYAL CHILDREN'S HOSPITAL FLEMINGTON RD	PARKVILLE				AUS	Allergy and Infectious Diseases Research	001	2	4/16/2024	NON-COMPETING CONTINUATION	$48,647
														Subtotal = $486,469

Issue Date FY: 2023 ( Subtotal = $472,269 )
2023	2023	MURDOCH CHILDRENS RESEARCH INSTITUTE	ROYAL CHILDRENS HOSPITAL FLEMINGTON RD	PARKVILLE				AUS	Allergy and Infectious Diseases Research	000	1	12/30/2022	NEW	$472,269
														Subtotal = $472,269

Grand Total All Awards = $1,444,875

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Assays for acceleration: from fit-for-purpose models to scalable assays of broad systemic and mucosal protection against all strains of Group A Streptococcus

Award Number: R01AI173567

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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