Thursday, November 21, 2024 11/21/2024

Methods to synthesize oligosaccharide-fusion protein conjugates and enhancement of their antigenicity

Award Number: R01AI148570
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 Carbohydrates have been used in some of the world most effective glycoconjugate vaccines. However, traditional glycoconjuates produced by oligosaccharide isolation have failed to produce effective vaccines against the ESKAPE pathogen Pseudomonas aeruginosa. ESKAPE pathogens are pathogens that have acquired extensive antimicrobial resistance (AMR) and are becoming increasingly difficult and in some cases impossible to treat. There is an urgent need to identity new approaches for controlling AMR which is projected to cause up to 10 million deaths annually and cost 100 trillion dollars in cumulative economic damage by the year 2050. This application addresses AMR by using a powerful soluble polymer-based synthetic method to chemically synthesize serotype-independent oligosaccharide epitopes from the lipopolysaccharide (LPS) of P. aeruginosa bacteria. In addition, we develop robust methods to site-specifically conjugate these synthetic oligosaccharide domains with protective fusion protein domains prepared by synthetic biology-based methods. We develop methods to further site-specifically conjugate these glycoconjugates with lipid adjuvants to form well-defined single molecule lipoglycoproteins. These materials will be used to determine the beneficial role of both the oligosaccharide and the protein in provoking a protective immune response. In addition, the work will allow mapping of the protective oligosaccharide and protein epitopes. The antigens are designed to overcome known obstacles to development of a protective immune response against this bacterium and to provide protection against multiple bacterial strains. A second aspect of the proposal is the systematic study of the resulting conjugates in mice that will lead to new approaches to enhance vaccine immunogenicity in humans. The approach takes advantage of naturally occurring antibodies in humans that can participate in enhancing the recognition of the vaccine by the immune system. This proposal takes advantage of a collaboration between investigators trained in organic chemistry, immunology, and molecular mechanisms of pathogenesis.


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: 2024 ( Subtotal = $465,901 )
2024	2024	UNIVERSITY OF TOLEDO	2801 W BANCROFT ST	TOLEDO	OH	43606	LUCAS	USA	Allergy and Infectious Diseases Research	000	5	1/24/2024	NON-COMPETING CONTINUATION	$419,311
2024	2024	UNIVERSITY OF TOLEDO	2801 W BANCROFT ST	TOLEDO	OH	43606	LUCAS	USA	Allergy and Infectious Diseases Research	001	5	5/20/2024	NON-COMPETING CONTINUATION	$46,590
														Subtotal = $465,901

Issue Date FY: 2023 ( Subtotal = $442,697 )
2023	2023	UNIVERSITY OF TOLEDO, THE	2801 W BANCROFT ST	TOLEDO	OH	43606	LUCAS	USA	Allergy and Infectious Diseases Research	000	4	11/23/2022	NON-COMPETING CONTINUATION	$442,697
														Subtotal = $442,697

Issue Date FY: 2022 ( Subtotal = $442,697 )
2022	2022	UNIVERSITY OF TOLEDO, THE	2801 W BANCROFT ST	TOLEDO	OH	43606	LUCAS	USA	Allergy and Infectious Diseases Research	000	3	12/22/2021	NON-COMPETING CONTINUATION	$442,697
														Subtotal = $442,697

Issue Date FY: 2021 ( Subtotal = $436,677 )
2021	2021	UNIVERSITY OF TOLEDO, THE	2801 W BANCROFT ST	TOLEDO	OH	43606	LUCAS	USA	Allergy and Infectious Diseases Research	000	2	12/18/2020	NON-COMPETING CONTINUATION	$436,677
														Subtotal = $436,677

Issue Date FY: 2020 ( Subtotal = $550,227 )
2020	2020	UNIVERSITY OF TOLEDO, THE	2801 W BANCROFT ST	TOLEDO	OH	43606	LUCAS	USA	Allergy and Infectious Diseases Research	000	1	12/31/2019	NEW	$550,227
2020	2020	UNIVERSITY OF TOLEDO, THE	2801 W BANCROFT ST	TOLEDO	OH	43606	LUCAS	USA	Allergy and Infectious Diseases Research	001	1	5/29/2020	NEW	$0
														Subtotal = $550,227

Grand Total All Awards = $2,338,199

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Methods to synthesize oligosaccharide-fusion protein conjugates and enhancement of their antigenicity

Award Number: R01AI148570

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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