Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Sex Determines Age-related Changes in the Repertoire and Function of Natural Antibodies Protective against Streptococcus pneumoniae with Increasing Age

Award Number: R01AI154539
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: 09/21/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2024

Group Awards By:

View Award Description

Sex Determines Age-related Changes in the Repertoire and Function of Natural Antibodies Protective against Streptococcus pneumoniae with Increasing Age - Project Summary/Abstract Streptococcus pneumoniae is the most common cause of pneumonia, leading to death in individuals over the age of 65 eight times more frequently than those aged 5-49, despite the long-standing availability of a vaccine for this age group (approved in 1983). In both murine and human systems, there is a greater incidence of, and susceptibility to, pneumococcal infection in males; nevertheless, the factors contributing to this difference between males and females is unknown. Therefore, the long-term goal of this study is to gain a greater understanding of the aging immune system in the context of sex, which will enable development of new preventative and/or treatment strategies of S. pneumoniae infection. Specifically, the goal of this proposal is to determine whether estrogen has an effect on a specific subset of B cells, B1a cells, which provide essential protection and therefore survival from S. pneumoniae infection through production of natural antibodies. Antibodies provide defense against infection by binding the pathogen and preventing infection of host cells. Natural antibodies are present in the absence of infection or intentional immunization. The unique ability of B1a cells to provide protection against S. pneumoniae is attributed to their production of natural antibodies, which have unique structural characteristics resulting from the fetal development of B1a cells. In addition to fetal development, B1 cell progenitors in adult bone marrow can also contribute to the B1a cell pool; however, the characteristics of fetal B1a cell derived natural antibodies are lost in these adult B1a cell derived natural antibodies. We have demonstrated natural serum IgM from aged male mice does not provide protection against S. pneumoniae infection. Unexpectedly, our preliminary results reveal differences in natural antibodies obtained from aged male and female B1a cells, in that age-related changes experienced by male B1a cell antibodies do not seem to occur in females. Yet, we do not know the role sex plays during the aging process to affect B1a cells over time resulting in a non-effective B1a cell derived natural antibody in aged males. We hypothesize estrogen affects the pool of natural antibodies capable of providing protection against S. pneumoniae in the aged. To test this hypothesis and determine if sex-related factors such as estrogen affect the ability of B1a cells to maintain protective natural IgM with age, we will perform the following aims: 1) Elucidate the role of estrogen in the production of natural IgM protective against S. pneumoniae infection in aged males and females, 2) Determine the role of estrogen in the development and selection of B1a cells with increasing age, and 3) Examine the effects of sex and estrogen exposure upon human B1 cell numbers and repertoire in young, middle aged, and aged donors. This project will determine the effect estrogen has on the ability of B1a cells to provide immediate protection from S. pneumoniae infection with increasing age. This further understanding of the aged immune system in the context of sex will likely suggest new prevention and/or treatments strategies of S. pneumoniae infection in both male and female elderly populations.


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 = -$576 )
2025	2023	WESTERN MICHIGAN UNIVERSITY HOMER STRYKER M.D. SCHOOL OF MEDICINE	1000 OAKLAND DR	KALAMAZOO	MI	49008	KALAMAZOO	USA	Allergy and Infectious Diseases Research	000	4	2/14/2025	NON-COMPETING CONTINUATION	-$576
														Subtotal = -$576

Issue Date FY: 2023 ( Subtotal = $377,500 )
2023	2023	WESTERN MICHIGAN UNIVERSITY HOMER STRYKER M.D. SCHOOL OF MEDICINE.	1000 OAKLAND DR	KALAMAZOO	MI	49008	KALAMAZOO	USA	Allergy and Infectious Diseases Research	000	4	8/9/2023	NON-COMPETING CONTINUATION	$377,500
														Subtotal = $377,500

Issue Date FY: 2022 ( Subtotal = $377,500 )
2022	2022	WESTERN MICHIGAN UNIVERSITY HOMER STRYKER M.D. SCHOOL OF MEDICINE.	1000 OAKLAND DR	KALAMAZOO	MI	49008	KALAMAZOO	USA	Allergy and Infectious Diseases Research	000	3	8/22/2022	NON-COMPETING CONTINUATION	$377,500
														Subtotal = $377,500

Issue Date FY: 2021 ( Subtotal = $377,500 )
2021	2021	WESTERN MICHIGAN UNIVERSITY SCHOOL OF MEDICINE	1000 OAKLAND DR	KALAMAZOO	MI	49008	KALAMAZOO	USA	Allergy and Infectious Diseases Research	000	2	8/16/2021	NON-COMPETING CONTINUATION	$377,500
														Subtotal = $377,500

Issue Date FY: 2020 ( Subtotal = $377,500 )
2020	2020	WESTERN MICHIGAN UNIVERSITY SCHOOL OF MEDICINE	1000 OAKLAND DR	KALAMAZOO	MI	49008	KALAMAZOO	USA	Allergy and Infectious Diseases Research	000	1	9/21/2020	NEW	$377,500
														Subtotal = $377,500

Grand Total All Awards = $1,509,424

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Sex Determines Age-related Changes in the Repertoire and Function of Natural Antibodies Protective against Streptococcus pneumoniae with Increasing Age

Award Number: R01AI154539

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: 09/21/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer