Friday, February 13, 2026 2/13/2026

Natural killer cell regulation of the germinal center HIV neutralizing antibody response

Award Number: R01AI147778
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: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Natural killer cell regulation of the germinal center HIV neutralizing antibody response - Project Summary/Abstract: HIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines, but are generated in approximately half of HIV-1-infected individuals after years of chronic infection. Definition of the mechanisms that enable bnAb development during infection will pave the way for vaccination strategies capable of eliciting bnAbs. Some reasons bnAbs are not readily induced are their requirement for high immunoglobulin gene somatic hypermutation that requires successive rounds of B cell affinity maturation in germinal centers and their limitation by host regulatory controls. We have recently identified that HIV-1-infected individuals who developed bnAbs have more dysfunctional natural killer (NK) cells as well as higher frequencies of circulating CD4+ T follicular helper (Tfh) cells that provide critical help to B cells. We further demonstrated that activated NK cells from HIV-seronegative donors could reduce Tfh cell numbers and decrease B cell activity in NK-Tfh- B cell co-cultures. These data led to the scientific premise of our proposal that NK cell dysregulation results in reduced NK cell constraints on Tfh availability which contributes to bnAb development during HIV-1 infection. This identified NK cells as a potential key regulator of the HIV-1 bnAb response. The overall objective of this proposal is to test our central hypothesis that transient blockade of NK cell immunoregulatory activity will create an immunological environment permissive for the development of HIV-1 bnAbs by increasing germinal center T and B cell responses. This hypothesis is supported by results from a preliminary study we have performed in rhesus macaques to address the effects of transient NK depletion on the response to HIV Envelope vaccination, where an increase in germinal center Tfh and B cell frequencies was observed in macaques that had NK cells depleted during HIV vaccination compared with HIV vaccinated animals without NK cell depletion. Our specific aims will test the following hypotheses: (Aim 1) NK cells from HIV-1-infected individuals generating bnAbs will have a more impaired immunoregulatory capacity than those from HIV- infected individuals without bnAbs; (Aim 2) We will define the critical NK cell receptor-Tfh ligands important for NK cell inhibition of Tfh and B cells; (Aim 3) Determine the mechanisms of transient NK cell depletion on the germinal center HIV-1 neutralizing antibody response. This project is innovative because we have identified that NK cell dysfunction contributes to HIV-1 bnAb development and have demonstrated in depletion of NK cells improves germinal center activity after immunization. This contribution is significant because identifying the molecular mechanisms and receptor-ligand interactions that mediate NK cell inhibition of Tfh and B cell responses and determining the effect of NK cell depletion or receptor blockade on germinal center B cell a Tfh cell repertoire and function in vivo will identify novel NK cell-targeting strategies that can be applied during HIV-1 vaccination to improve immune responses.


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: 2026 ( Subtotal = $0 )
2026	2024	CHILDRENS MERCY HOSPITAL	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	000	5	1/23/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $653,670 )
2024	2024	CHILDRENS MERCY HOSPITAL	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	001	5	5/15/2024	NON-COMPETING CONTINUATION	$65,366
2024	2024	CHILDRENS MERCY HOSPITAL	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	000	5	11/17/2023	NON-COMPETING CONTINUATION	$588,304
														Subtotal = $653,670

Issue Date FY: 2023 ( Subtotal = $792,838 )
2023	2023	CHILDREN'S MERCY HOSPITAL, THE	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	000	4	11/9/2022	NON-COMPETING CONTINUATION	$666,211
2023	2023	CHILDRENS MERCY HOSPITAL	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	001	4	8/16/2023	NON-COMPETING CONTINUATION	$126,627
														Subtotal = $792,838

Issue Date FY: 2022 ( Subtotal = $1,150,526 )
2022	2022	CHILDREN'S MERCY HOSPITAL, THE	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	001	3	11/10/2021	NON-COMPETING CONTINUATION	$677,049
2022	2022	CHILDREN'S MERCY HOSPITAL, THE	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	002	3	8/19/2022	SUPPLEMENT FOR EXPANSION	$473,477
2022	2021	CHILDREN'S MERCY HOSPITAL, THE	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	000	2	10/13/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,150,526

Issue Date FY: 2021 ( Subtotal = $687,036 )
2021	2021	CHILDREN'S MERCY HOSPITAL, THE	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	000	2	11/24/2020	NON-COMPETING CONTINUATION	$687,036
														Subtotal = $687,036

Issue Date FY: 2020 ( Subtotal = $857,694 )
2020	2020	CHILDREN'S MERCY HOSPITAL, THE	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	001	1	4/16/2020	NEW	$580,305
2020	2020	CHILDREN'S MERCY HOSPITAL, THE	2401 GILLHAM RD	KANSAS CITY	MO	64108	JACKSON	USA	Allergy and Infectious Diseases Research	000	1	11/28/2019	NEW	$277,389
														Subtotal = $857,694

Grand Total All Awards = $4,141,764

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Natural killer cell regulation of the germinal center HIV neutralizing antibody response

Award Number: R01AI147778

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: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer