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

CELL-MEDIATED PROTECTION AGAINST PNEUMONIC PLAGUE

Award Number: R01AI061577
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: 09/30/2004
PERIOD OF PERFORMANCE END DATE: 02/28/2015

Group Awards By:

View Award Description

CELL-MEDIATED PROTECTION AGAINST PNEUMONIC PLAGUE - DESCRIPTION (provided by applicant): Yersinia pestis (Yp) - one of the world's most virulent human pathogens - is the gram-negative bacterium that causes pneumonic plague. Virulent, antibiotic-resistant, Yp strains exist and Cold War scientists devised means to effectively aerosolize Yp. Thus, there is grave concern that Yp will be exploited as a bioweapon. To thwart that possibility, it is essential that we develop effective countermeasures. Recent primate studies suggest that the leading vaccine candidate - a recombinant F1-V fusion protein (rF1V) - may not provide sufficient protection. Moreover, resourceful bioweapon engineers could circumvent this vaccine with an F1-negative V-variant strain. While the rF1V vaccine primarily stimulates antibody-mediated humoral immunity, T cell-dependent cellular immunity comprises a second means by which vaccines can prime long-lived protection. However, it is widely accepted that the extreme virulence of Yp results, in large part, from plasmid-encoded factors that dampen inflammation and debilitate phagocytes, thereby compromising cell-mediated defense. Thus, plague vaccine researchers have devoted little attention to cellular immunity. Nevertheless, the Progress Report demonstrates that T cells can protect against pulmonary Yp infection. As such, we propose that next-generation pneumonic plague vaccines should strive to prime both humoral and cellular immunity, as well as incorporate new antigens. In Aim 1 of this application for grant renewal, we will directly measure the extent to which pulmonary Yp infection suppresses na¿ve and effector/memory T cell responses in vivo and identify mechanisms underlying any suppression that exists. In Aim 2, we will generate T cell clones that confer protection in mice, identify their cognate protein antigens using a series of complementary genetic, molecular and biochemical approaches, and then quantify the utility of these antigens as vaccines. We will also determine which antigens confer synergistic protection when combined with V-specific antibodies. Our findings will allow next-generation F1/V-based vaccines to harness both the neutralizing capacities of antibodies and the antimicrobial capacities of cellular immunity, while simultaneously reducing opportunities for circumvention by bioweapon engineers. Moreover, our studies will also generate powerful new tools for deciphering the fascinating interplay between Yp virulence factors and host defense mechanisms, thereby advancing basic research aimed at exploiting cellular immunity for defense against virulent bacterial pathogens that infect the lung. PUBLIC HEALTH RELEVANCE: To counter the potential use of pneumonic plague as a bioweapon, it is essential that we develop an effective vaccine. Recent animal studies suggest that the current vaccine candidate, which primarily stimulates B cells to make plague-fighting antibodies, may not suffice. This proposal aims to fundamentally improve that vaccine by incorporating the protective capacities of both B and T cells.


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: 2013 ( Subtotal = $456,934 )
2013	2013	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	9	6/5/2013	NON-COMPETING CONTINUATION	$19,445
2013	2013	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	9	1/24/2013	NON-COMPETING CONTINUATION	$437,489
														Subtotal = $456,934

Issue Date FY: 2012 ( Subtotal = $469,961 )
2012	2012	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	8	2/10/2012	NON-COMPETING CONTINUATION	$469,961
														Subtotal = $469,961

Issue Date FY: 2011 ( Subtotal = $470,264 )
2011	2011	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	7	1/24/2011	NON-COMPETING CONTINUATION	$427,513
2011	2011	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	7	6/14/2011	NON-COMPETING CONTINUATION	$42,751
														Subtotal = $470,264

Issue Date FY: 2010 ( Subtotal = $489,018 )
2010	2010	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	6	3/15/2010	NON-COMPETING CONTINUATION	$489,018
														Subtotal = $489,018

Issue Date FY: 2009 ( Subtotal = $432,754 )
2009	2009	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	001	5	2/16/2009	COMPETING CONTINUATION	$0
2009	2009	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	5	2/11/2009	COMPETING CONTINUATION	$432,754
														Subtotal = $432,754

Issue Date FY: 2007 ( Subtotal = $361,342 )
2007	2007	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	4	12/8/2006	NON-COMPETING CONTINUATION	$361,342
														Subtotal = $361,342

Issue Date FY: 2006 ( Subtotal = $361,296 )
2006	2006	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	3	2/3/2006	NON-COMPETING CONTINUATION	$361,296
														Subtotal = $361,296

Issue Date FY: 2005 ( Subtotal = $359,214 )
2005	2005	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Microbiology and Infectious Diseases Research	000	2	3/24/2005	NON-COMPETING CONTINUATION	$359,214
														Subtotal = $359,214

Issue Date FY: 2004 ( Subtotal = $378,545 )
2004	2004	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Microbiology and Infectious Diseases Research	000	1	9/27/2004	NEW	$378,545
														Subtotal = $378,545

Grand Total All Awards = $3,779,328

Top

All Categories

About

Search

Reports

Data Submission

Award Information

CELL-MEDIATED PROTECTION AGAINST PNEUMONIC PLAGUE

Award Number: R01AI061577

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: 09/30/2004

PERIOD OF PERFORMANCE END DATE: 02/28/2015

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer