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Defining Chlamydia trachomatis adhesion factor epitope-specific antibody responses, functionality, and roles in protection against urogenital infection

Award Number: F30AI156995
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/18/2021
PERIOD OF PERFORMANCE END DATE: 09/05/2023

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Defining Chlamydia trachomatis adhesion factor epitope-specific antibody responses, functionality, and roles in protection against urogenital infection - PROJECT SUMMARY Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection worldwide and causes serious medical complications in women, including pelvic inflammatory disease, ectopic pregnancy, and infertility. Therefore, a vaccine is urgently needed. One obstacle to successful vaccine development is a lack of a comprehensive understanding of the protective immune response to Ct infection, including the role of epitope-specific antibodies. The overall objective of this fellowship proposal is to finely map the antibody response in women with an acute history of Ct infection, determine immunodominant epitopes of Ct antigens, investigate differential antibody responses between women with a positive Ct infection outcome (defined as no Ct reinfection at 3-months follow-up or spontaneous resolution of Ct infection without antibiotic treatment) and women who experience Ct reinfection, and determine the functionality and protective capacity of these antibody responses. The central hypothesis to be tested is that antibody responses will differ between patients who had a positive Ct infection outcome than those who experienced a reinfection of Ct and that these epitope- specific antibodies to adhesion factors of Ct will play an important role in protection (binding to Ct-infected cells, neutralization, antibody-mediated neutrophil killing, and protection from a Ct challenge in murine models). The long-term goal is to inform vaccine design through better understanding of protective immune responses, culminating in an effective Ct vaccine. The following specific aims will be used to test the hypothesis: Specific Aim 1: Define the natural serum antibody response to urogenital Ct infection in women. Utilizing Deep Sequence-Coupled Biopanning, a novel technology that uses a small amount of human sera to finely map the antibody response at an epitope-level, I will elucidate the natural antibody response to Ct infection. This will empirically determine immunodominant epitopes and B cell epitopes to 24 Ct antigens. I will also define differential antibody responses between women who experienced a positive Ct infection outcome compared to those who experienced a Ct reinfection within 3-months of antibiotic treatment. Specific Aim 2: Investigate Ct adhesion factor epitope-specific antibody functions. Antibodies to immunodominant epitopes and differential antibody response between patient cohorts (SA1) will be tested for functionality to determine protective capacity against Ct infection. Using in vitro techniques, I will determine if these epitope-specific antibodies can bind to Ct, have neutralizing capacity, and can function in antibody- mediated neutrophil Ct killing. I will also determine if these antibodies can protect against a Ct infection in a murine model by monitoring Ct infection, bacterial shedding, Ct clearance, and upper genital tract pathology. Together, this proposal will investigate the specificity, functionality, and role of epitope-specific antibodies in protection against Ct infection and has the potential to significantly advance the Ct field by understanding protective immune responses and informing future vaccine design.


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 = -$19,632 )
2024	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	000	3	7/24/2024	NON-COMPETING CONTINUATION	-$19,632
														Subtotal = -$19,632

Issue Date FY: 2023 ( Subtotal = $33,236 )
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	000	3	1/11/2023	NON-COMPETING CONTINUATION	$32,630
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	001	3	2/23/2023	NON-COMPETING CONTINUATION	$606
														Subtotal = $33,236

Issue Date FY: 2022 ( Subtotal = $43,542 )
2022	2022	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	000	2	12/22/2021	NON-COMPETING CONTINUATION	$42,826
2022	2022	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	001	2	5/24/2022	NON-COMPETING CONTINUATION	$716
														Subtotal = $43,542

Issue Date FY: 2021 ( Subtotal = $42,826 )
2021	2021	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	001	1	2/18/2021	NEW	$516
2021	2021	UNIVERSITY OF NEW MEXICO	2500 MARBLE DR NE	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Allergy and Infectious Diseases Research	000	1	12/28/2020	NEW	$42,310
														Subtotal = $42,826

Grand Total All Awards = $99,972

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Defining Chlamydia trachomatis adhesion factor epitope-specific antibody responses, functionality, and roles in protection against urogenital infection

Award Number: F30AI156995

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/18/2021

PERIOD OF PERFORMANCE END DATE: 09/05/2023

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