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A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum.

Award Number: U19AI144177
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum. - The scientific premise of this CRC proposal rests upon our three decades of work defining the molecular architecture of the outer membrane (OM) of Treponema pallidum subsp. pallidum (TPA), coupled with our recent successes combining bioinformatics, biophysical techniques, and localization methods with live TPA to topologically characterize TPA outer membrane proteins (OMPs) and define the syphilis spirochete's `OMPeome'--its repertoire of OMPs. Its central hypothesis is that the principal targets for a syphilis vaccine reside within TPA's repertoire of rare outer membrane proteins (OMPs). The projects in the proposal employ three different, but closely integrated, strategies to exploit this novel application of reverse vaccinology to develop a syphilis vaccine with global efficacy. Project 1 is `immune-agnostic', selecting leading vaccine candidates based on genomic sequences, bioinformatics, biophysical analysis, and structural modeling. Project 2 takes its cue from the human immune system: since the large majority of untreated individuals do eventually control TPA infection, it stands to reason that OMPs targeted by opsonic antibodies6-9 should be excellent vaccine candidates. Project 3 borrows a page from the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) `book', using state-of-the art recombinant B cell and phage technology to generate broadly reactive, opsonic monoclonal antibodies directed against surface-exposed loops of TPA OMPs. The extraordinary deep sequencing capabilities of the Genetics and Genomics core will provide the data needed to tailor these approaches for efficacy on a global scale. This CRC, led by two senior investigators, established collaborators with complementary clinical and research backgrounds, pulls together (a) the unique capabilities of the Spirochete Research Laboratories at UConn Health; (b) the world-class B cell technology and vaccine research infrastructure of the Duke Human Vaccine Institute (DHVI); (c) the international health infrastructure and expertise of the University of North Carolina Institute for Global Health and Infectious Diseases; and (d) the unparalleled knowledge of TPA genomics at Masaryk University to achieve our long-term objective. The Administrative Core will provide the managerial oversight needed to integrate these capabilities and resources to strengthen existing collaborations and foster new ones within the Center and with other CRCs. The ultimate strength of this CRC is the diversity and complementarity of approaches, technologies, resources, and expertise it marshals to interrogate the TPA OMPeome to achieve our long-term goals. An effective syphilis vaccine would represent a triumph of biomedical research over an ailment that for more than five centuries has exacted a heavy toll on humanity4,5 and that has defied conventional public health strategies for containment. If successful, the scientific and public health impact of our approach to reverse vaccinology will extend well beyond syphilis, establishing a paradigm applicable to other recalcitrant organisms.


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	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Allergy and Infectious Diseases Research	000	5	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Allergy and Infectious Diseases Research	000	5	3/1/2024	NON-COMPETING CONTINUATION	$0
2024	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Allergy and Infectious Diseases Research	001	5	3/1/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $2,242,259 )
2023	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Allergy and Infectious Diseases Research	004	5	4/24/2023	NON-COMPETING CONTINUATION	$2,148,172
2023	2023	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	003	4	2/28/2023	SUPPLEMENT FOR EXPANSION	$18,704
2023	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Allergy and Infectious Diseases Research	005	5	4/25/2023	SUPPLEMENT FOR EXPANSION	$75,383
2023	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	001	4	12/23/2022	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	000	4	11/16/2022	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	002	4	1/5/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,242,259

Issue Date FY: 2022 ( Subtotal = $2,273,500 )
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	001	4	5/4/2022	NON-COMPETING CONTINUATION	$2,175,925
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	002	4	8/26/2022	SUPPLEMENT FOR EXPANSION	$97,575
2022	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	000	3	1/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,273,500

Issue Date FY: 2021 ( Subtotal = $2,162,304 )
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	001	3	4/29/2021	NON-COMPETING CONTINUATION	$2,162,304
2021	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	000	2	11/3/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,162,304

Issue Date FY: 2020 ( Subtotal = $2,219,208 )
2020	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	000	2	4/13/2020	NON-COMPETING CONTINUATION	$2,219,208
														Subtotal = $2,219,208

Issue Date FY: 2019 ( Subtotal = $2,334,857 )
2019	2019	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	001	1	6/11/2019	NEW	$1,255
2019	2019	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Allergy and Infectious Diseases Research	000	1	4/30/2019	NEW	$2,333,602
														Subtotal = $2,334,857

Grand Total All Awards = $11,232,128

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A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum.

Award Number: U19AI144177

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 05/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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