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Does repeated influenza vaccination constrain influenza immune responses and protection?

Award Number: R01AI141534
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/03/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Does repeated influenza vaccination constrain influenza immune responses and protection? - PROJECT SUMMARY/ABSTRACT Over 140 million Americans are among the more than 500 million people who receive influenza vaccines an- nually. An important subgroup are healthcare workers (HCWs) for whom vaccination is recommended, and sometimes mandated, to protect themselves and vulnerable patients from influenza infection. However, there have been no large, long term studies of HCWs to support the effectiveness of these policies. HCWs are now a highly vaccinated population, the effects of which are also poorly understood. Mounting evidence suggests an- tibody responses to vaccination can be attenuated with repeated vaccination, which is corroborated by reports of poor vaccine effectiveness among the repeatedly vaccinated. Thus, there is a compelling need to directly evaluate HCW vaccination programs. The long term goal is to improve the efficient and effective use of influ- enza vaccines. The objectives of this application are to understand the long-term consequences of repeated annual influenza vaccination among HCWs and to use statistical and mathematical modeling to elucidate the immunological processes that underlie vaccination responses and their implications for vaccination effective- ness. These objectives will be achieved by pursuing three specific aims: 1) To study the immunogenicity and effectiveness of influenza vaccination by prior vaccination experience; 2) To characterize immunological pro- files associated with vaccination and infection; and 3) To evaluate the impact of immunity on vaccination effec- tiveness. Under Aim 1, a cohort of hospital workers will be recruited and followed for up to 4 years to assess their pre- and post-vaccination and post-season antibody responses, and their risk of influenza infection. These outcomes will be compared by vaccination experience, classified as frequently vaccinated (received ≥3 vac- cines in the past 5 years), infrequently vaccinated (<3 vaccinations in past 5 years), vaccinated once, vaccine- naïve and unvaccinated. In Aim 2, intensive cellular and serological assessments will be conducted to dissect the influenza HA-reactive B cell and antibody response, and build antibody landscapes that typify the different vaccination groups. In Aim 3, the data generated in Aims 1 and 2 will be used to develop a mathematical mod- el that considers prior infection, vaccination history, antibody kinetics, and antigenic distance to understand the effects of repeated vaccination on vaccine effectiveness. This approach is innovative because it will provide insights into the effect of complex immunological dynamics on infection outcomes, thereby representing a nov- el departure from previous studies, which have ignored these difficult-to-measure processes. Completion of the proposed research will provide evidence to inform decisions about continued support for influenza vaccination programs among HCWs and general policies for annual influenza vaccination, as well as much-needed clarity about the effects of repeated vaccination.


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 = -$20,739 )
2025	2020	UNIVERSITY OF MELBOURNE	RAYMOND PRIESTLEY BLDG UNIV OF MELB	MELBOURNE	VICTORIA			AUS	Allergy and Infectious Diseases Research	000	2	1/27/2025	SUPPLEMENT FOR EXPANSION	-$20,739
														Subtotal = -$20,739

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Allergy and Infectious Diseases Research	000	5	2/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $129,250 )
2023	2023	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Allergy and Infectious Diseases Research	000	5	6/27/2023	NON-COMPETING CONTINUATION	$129,250
2023	2020	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Allergy and Infectious Diseases Research	001	2	6/29/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $129,250

Issue Date FY: 2022 ( Subtotal = $1,325,203 )
2022	2022	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Allergy and Infectious Diseases Research	000	4	8/3/2022	NON-COMPETING CONTINUATION	$1,325,203
2022	2022	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Allergy and Infectious Diseases Research	001	4	9/9/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,325,203

Issue Date FY: 2021 ( Subtotal = $951,396 )
2021	2021	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Allergy and Infectious Diseases Research	000	3	7/8/2021	NON-COMPETING CONTINUATION	$951,396
2021	2020	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC			AUS	Allergy and Infectious Diseases Research	001	2	9/3/2021	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $951,396

Issue Date FY: 2020 ( Subtotal = $1,742,489 )
2020	2020	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3010		AUS	Allergy and Infectious Diseases Research	004	2	7/10/2020	SUPPLEMENT FOR EXPANSION	$520,671
2020	2020	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3010		AUS	Allergy and Infectious Diseases Research	001	1	5/13/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2020	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3010		AUS	Allergy and Infectious Diseases Research	003	2	6/26/2020	NON-COMPETING CONTINUATION	$985,423
2020	2020	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3010		AUS	Allergy and Infectious Diseases Research	000	1	5/12/2020	SUPPLEMENT FOR EXPANSION	$236,395
2020	2019	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3010		AUS	Allergy and Infectious Diseases Research	002	1	6/11/2020	NEW	$0
														Subtotal = $1,742,489

Issue Date FY: 2019 ( Subtotal = $773,603 )
2019	2019	UNIVERSITY OF MELBOURNE	GRATTAN ST	PARKVILLE	VIC	3010		AUS	Allergy and Infectious Diseases Research	000	1	7/3/2019	NEW	$773,603
														Subtotal = $773,603

Grand Total All Awards = $4,901,202

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Does repeated influenza vaccination constrain influenza immune responses and protection?

Award Number: R01AI141534

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/03/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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