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Identifying mechanisms and correlates of long-lasting vaccine-induced immunity to whooping cough

Award Number: U01AI141995
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Recent years witnessed a worldwide reemergence of Pertussis (whooping cough, PT) despite widespread vaccination. In the mid-1990s, concerns over vaccine-related side effects prompted the widespread replacement of the whole-cell Pertussis (wP) vaccine in favor of a safer acellular Pertussis (aP) vaccine. Unexpectedly, whooping cough cases recently increased, particularly in teenagers. As this age bracket corresponds to the first cohorts of children that were aP-vaccinated in the mid-1990s as newborns, it is suspected that the switch to the aP vaccine may underlie this rise in morbidity, which is further supported by epidemiologic evidence comparing introduction of the aP vaccine and resurgence of PT cases across different countries. The goal of this proposal is identifying the mechanisms and correlates of long-lasting vaccine- induced immunity. Our approach is to compare individuals born before 1995 that were vaccinated in infancy with wP, with individuals born in 1996 or later that were vaccinated with aP in infancy. These young adults correspond to the population and age group in which the increased disease incidence is noted. Remarkably, we detect drastic qualitative differences in the immune phenotypes of the two populations despite the fact that the original aP- or wP-priming occurred more than 18 years ago. Ex vivo analysis of PT-specific T cells revealed that original aP priming is mostly associated with IL-4, TGF-ß and IL-9 responses while original wP priming is associated with IFNg and IL-17 responses. Furthermore, after repeated aP vaccination boosts, T cells originally primed with aP become associated with diminished capacity to respond to a boost in vivo and have altered proliferative capacity. Here, we plan to define the transcriptional response to vaccine boost in PBMC from donors originally primed with aP vs. wP and identify the cell types associated with differential responses (Aim 1). Following this initial “broad net” characterization, we will hone in the characterization of differences in PT-specific memory T cell responses in aP vs. wP donors (Aim2) and characterize the molecular mechanisms of differences in APC-priming of T cells in aP- vs. wP-vaccinated donors (Aim 3). Our study will be the first to characterize the interplay of APC and T cell response, comparing the outcome of priming with two vaccines associated with differential protective efficacy. The results will have implications for specifically understanding the immunological mechanisms associated with Pertussis vaccination and more generally defining the mechanisms of durable vaccine efficacy.


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: 2023 ( Subtotal = $823,202 )
2023	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	003	5	11/2/2022	NON-COMPETING CONTINUATION	$823,202
2023	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	4	10/18/2022	NON-COMPETING CONTINUATION	$0
2023	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	3	10/17/2022	NON-COMPETING CONTINUATION	$0
2023	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	10/14/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $823,202

Issue Date FY: 2022 ( Subtotal = $823,202 )
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	10/29/2021	NON-COMPETING CONTINUATION	$823,202
														Subtotal = $823,202

Issue Date FY: 2021 ( Subtotal = $823,202 )
2021	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	3	11/18/2020	NON-COMPETING CONTINUATION	$823,202
														Subtotal = $823,202

Issue Date FY: 2020 ( Subtotal = $823,202 )
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	1/17/2020	NON-COMPETING CONTINUATION	$823,202
2020	2019	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	11/14/2019	NEW	$0
														Subtotal = $823,202

Issue Date FY: 2019 ( Subtotal = $822,827 )
2019	2019	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	1	6/6/2019	NEW	$0
2019	2019	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	12/6/2018	NEW	$822,827
														Subtotal = $822,827

Grand Total All Awards = $4,115,635

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Identifying mechanisms and correlates of long-lasting vaccine-induced immunity to whooping cough

Award Number: U01AI141995

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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