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IMMUNOPATHOGENESIS OF CHRONIC GRAFT REJECTION

Release Date:  May 30, 2000

RFA:  AI-00-013

National Institute of Allergy and Infectious Diseases
(http://www.niaid.nih.gov)
National Heart, Lung, and Blood Institute
(http://www.nhlbi.nih.gov)

Letter of Intent Receipt Date:  September 1, 2000
Application Receipt Date:       October 23, 2000

APPLICATIONS IN RESPONSE TO THIS REQUEST FOR APPLCATIONS (RFA) MUST BE 
PREPARED USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC 
INSTRUCTIONS FOR COMPLETING THE APPLICATIONS ARE IN AN NIAID BROCHURE 
ENTITLED  INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS. 

PURPOSE

The Division of Allergy, Immunology and Transplantation (DAIT) of the 
National Institute of Allergy and Infectious Diseases (NIAID), and the 
Divisions of Heart and Vascular Diseases (DHVD) and Lung Diseases (DLD) 
of the National Heart, Lung, and Blood Institute (NHBLI) invite 
applications for program projects in the immunopathogenesis of chronic 
graft rejection.  Programs should be designed to: elucidate the cellular 
and molecular mechanisms involved in chronic allograft rejection; 
implement new, or improve upon existing therapeutic approaches to 
enhance graft survival; or, develop new prognostic tools which will aid 
in diagnosing the outcome of allograft transplant.  

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a 
PHS-led national activity for setting priority areas.  This Request for 
Applications (RFA),  Immunopathogenesis of Chronic Graft Rejection , is 
related to: Heart Disease and Stroke, Respiratory Diseases, Diabetes and 
Chronic Disabling Diseases.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople/

ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic, for-profit and non-profit 
organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and 
eligible agencies of the Federal government. Multi-institutional 
applications are acceptable and encouraged.  Foreign institutions are 
not eligible to apply.  Racial/ethnic minority individuals, women, and 
persons with disabilities are encouraged to apply as Principal 
Investigators.
 
MECHANISM OF SUPPORT

The mechanism of support will be the program project (P01) grant. This 
type of award supports broadly based multidisciplinary research programs 
that have a well-defined central research focus or objective. An 
important feature of the program project is that the interrelationships 
of the individual scientifically meritorious projects will result in a 
greater contribution to the overall program goals than if each project 
were pursued individually. Standard NIH policy requires P01 applications 
to consist of a minimum of three interrelated individual research 
projects that contribute to the program objective.  This type of award 
also can provide support for certain common resources termed cores. Such 
resources should be utilized by two or more projects within the award.  
Responsibility for the planning, direction, and execution of the 
proposed project will be solely that of the applicant.  The total 
project period may not exceed 5 years.  The anticipated award date is 
July 1, 2001.

FUNDS AVAILABLE 

The estimated total funds [direct & facilities + administration (F&A)] 
available for the first year of support for this RFA will be $5 million.  
In fiscal year 2001, the NIAID and the NHLBI plan to make approximately 
4 awards related to this RFA.  This level of support is dependent on the 
receipt of a sufficient number of applications of high scientific merit.  
Applications in excess of $1,250,000 in total (direct and F&A) costs in 
the first year will be returned as non-responsive.  Because the nature 
and scope of the research proposed may vary, it is anticipated that the 
size of each award will also vary. 

The usual NIH policies governing grants administration and management 
will apply.  Although this program is provided for in the financial 
plans of the NIAID and the NHBLI, awards pursuant to this RFA are 
contingent upon the availability of funds for this purpose.  Funding 
beyond the first and subsequent years of the grant will be contingent 
upon satisfactory progress during the preceding years and availability 
of funds.  At this time, the NIAID and NHLBI have not determined whether 
or how this solicitation will be continued beyond the present RFA.

RESEARCH OBJECTIVES

Background

With the advent of modern immunosuppressive therapies, one-year post-
engraftment survival approaches 90% for some organs.  However, long-term 
graft survival still remains poor, with 25% to 65% of all grafts failing 
within five years post-transplantation.  While many of the pathological 
mechanisms which cause acute rejection have been defined and are 
effectively treated or prevented with standard immunosuppressive 
therapies and modern HLA typing techniques, these therapies have not 
significantly improved long-term clinical outcomes for many transplant 
patients.  

The complex, multistage processes that result in chronic rejection of 
vascularized allografts are poorly understood.  While the determination 
of organ failure often relies on measurable physiological parameters, 
the early stages of chronic rejection are difficult to diagnose. 
Detection requires invasive procedures to obtain graft biopsies for 
histological evaluation.  Organs undergoing chronic rejection manifest 
some common pathologic criteria such as: progressive vascular 
obliteration; infiltration of immunocytes; interstitial and tubular 
atrophy; graft arteriosclerosis; and a marked fibrotic response.  The 
cellular and molecular mechanisms underlying these histopathological 
hallmarks remain obscure.

Research Objectives and Scope

Organ transplantation is the definitive therapy for most forms of end-
stage organ disease; however, chronic graft rejection, the deleterious 
effects of global, life-long immunosuppressive therapy, and the shortage 
of donor organs continue to limit its success.  Chronic graft rejection 
is the primary obstacle to long-term successful organ transplantation.  
While the armamentarium of immunosuppressive agents is impressive and 
the future prospect of tolerance induction to alleviate allograft 
rejection holds considerable promise, little is known about the 
pathologic mechanisms that effect chronic rejection.  To better 
integrate basic science and clinical medicine, this RFA seeks to focus 
these disciplines on the pathogenesis of chronic graft rejection, the 
processes which foreshadow rejection of allografts long-term, and the 
development of diagnostic procedures which will aid in predicting the 
prognosis of allograft transplants.  To this end, this RFA will fund 
research to: 1) elucidate the cellular and molecular events during the 
induction and effector phases of chronic solid organ graft rejection; 2) 
develop improved therapeutic approaches to enhance long-term graft 
survival; and 3) develop better prognostic tests to define and predict 
outcomes of allograft transplants.              

Many cell-cell, cell-matrix, and intracellular pathways have been 
implicated in the complex pathogenesis of chronic rejection.  Recent 
studies have focused on chemokine/growth factor-receptor intracellular 
signaling pathways and on genes induced during the early onset of 
rejection.  These pathways and genes lend themselves as targets for 
pharmacological and therapeutic intervention for both early diagnosis 
and possible prevention of graft rejection.  In addition, cell-cell 
interaction between T cells, macrophages, and endothelial cells and 
interactions of cells with the extracellular matrix have been implicated 
in the onset and progression of chronic rejection.  Thus, studies 
focused on these and other relevant cellular and molecular pathways that 
can serve as potential targets for intervention are of major interest.

Applications that capitalize on the strengths of collaboration between 
physicians and scientists to maximize the potential for discovering 
novel approaches relevant to transplantation for human diseases are 
strongly encouraged.  To foster the teamwork between basic scientists 
and transplant clinicians, NIH is especially interested in program 
projects that define the pathogenesis of chronic graft rejection in 
humans.  Areas of particular interest are: identification of the targets 
recognized by the immune response in chronic rejection; definition of 
the relative contributions of immunocytes to the process of chronic 
rejection; studies of the response of targets cells (e.g. endothelial 
cells, smooth muscle cells) to lymphocytes, cytokines and growth 
factors; delineation of the molecular process(es) of chronic rejection, 
including studies of cytokines, infiltrating cell types, and methods to 
attenuate the actions of these cells and their products; development of 
new therapeutic approaches and improvement of existing therapeutic 
approaches for the treatment and/or prevention of chronic rejection. 

Examples of relevant studies include, but are not limited to, the 
following:
o  Recent scientific findings have highlighted the involvement of T 
cells, macrophages and their respective gene-products as causal for 
chronic rejection.  The interaction of these cells and their factors 
with endothelial cells of the allograft may, in part, determine the 
success of the match.  Studies which further analyze the infiltrating 
cellular components and their soluble mediators in in vivo human models 
are encouraged.
o  Cytokines are expressed in heart, kidney, lung, liver and skin 
allografts following engraftment and during acute and chronic rejection.  
While the majority of information concerning cytokine biology in 
transplantation has come from animal models, little is known about the 
role of cyokines in human allograft rejection.  Cytokines and growth 
factors may play important mechanistic roles in transplant rejection.  
For example, IL-2, IL-6, IL-10, IL-1beta and TNF-alpha have been 
implicated in the pathogenesis of arteriosclerosis, and IL-4, TGF-beta 
may be involved in chronic allograft nephropathy.  Alternatively, the 
mediators might serve as diagnostic indicators for the analysis of 
allograft rejection or graft dysfunction.  A better understanding of the 
role these factors play in chronic rejection may provide justification 
for their use as interventional targets.
o  Certain solid organ allografts display alterations in adhesion 
molecules and extracellular matrix (ECM) components upon rejection. 
However, it has yet to be determined whether these alterations are a 
consequence or a cause of the pathogenesis of allograft rejection.  If 
causal in nature, could these molecules be used as targets or markers to 
prevent chronic rejection?  For example, in several organs, upregulation 
of endothelial adhesion molecules in the vascularized allograft is 
hypothesized to function in T cell recruitment to the graft site.  
Analysis of T cell:endothelial cell interactions in vivo and new 
information concerning the potential inhibition of such associations by 
anti-ICAM-1, -VCAM, or  E-selectin may lead to strategies to decrease 
the risk of graft failure.
o  Although the long-term rejection of allografts is sometimes 
accompanied by the presence of infectious agents, the role of infections 
in chronic rejection is poorly understood.  Recent studies have 
demonstrated a correlation between the presence of certain pathogens 
(e.g., cytomegalovirus, Mycobacterium tuberculosis, and Microsporidia) 
and a poor prognosis for long-term graft survival.  Do these pathogens 
 ignite  an immune response which is detrimental to the allograft?  Is 
the pathogenesis by which infectious agents  induce  chronic rejection 
similar/identical to  naturally  occurring chronic rejection in the 
absence of infection?  Studies which aim to analyze the basic science 
behind the pathogenesis, with the goal of clinical intervention, are 
encouraged.       
o  With the aim of developing new approaches, or improving existing 
approaches for the early detection of chronic organ rejection, 
applicants are encouraged to create and test novel,  non-invasive  
diagnostic techniques for the early detection of chronic rejection.  
Technical applications are sought which partner basic science principles 
with clinical approaches.  These techniques are particularly needed in 
the post-transplantation period during which the early stages of chronic 
rejection should be defined, characterized and potentially eliminated.  

SPECIAL AREAS OF INTEREST

Heart

A number of cardiac diseases result in heart failure, for which cardiac 
transplantation is the only successful treatment.  The primary 
indications for heart transplantation are coronary artery disease and 
cardiomyopathy in adults, and congenital heart disease and 
cardiomyopathy in children.  Nearly 5 million people in the United 
States have some form of heart failure and 20,000 to 40,000 of these 
could benefit from a heart transplant. In patients who survive the first 
year after transplant, chronic rejection is the major cause of death, 
arising in 50-60 percent of patients surviving five years post-
transplant. Chronic rejection is manifested in the coronary arteries of 
the transplanted heart as a concentric and diffuse intimal hyperplasia 
such that distal portions of the coronary vessels occlude.  There are 
multiple theories as to the etiology of this disease, but few confirmed 
risk factors have been defined. There are no proven therapies to prevent 
or treat chronic rejection, and the only  cure  is re-transplantation.  
Current methods of diagnosis include intravascular ultrasound and/or 
coronary angioscopy.  

Chronic rejection in heart transplantation is recognized by a variety of 
names: cardiac allograft vasculopathy (CAV), cardiac transplant 
atherosclerosis, and accelerated graft arteriosclerosis.  The disease is 
believed to be caused by the immune response of the recipient to the 
donor organ and such responses have been shown to involve humoral and 
cellular immune components, as well as, complement, cytokines and growth 
factors.  More studies are needed to: 1) define the risk factor(s) that 
contribute to CAV and their mechanism(s) of action; 2) develop new or 
improved methods to predict and diagnose early onset of CAV; and 3) 
identify viable targets for prevention and/or treatment of chronic 
rejection in the heart; and 4) determine the role, if any, of non-
antigen specific responses, such as ischemia/reperfusion injury or brain 
death, in the development of chronic rejection. 

Kidney

Kidney disease is a severe and costly public health problem that is 
increasing in the U.S.  An estimated 10.9 million Americans suffer from 
kidney disease, including more than 360,000 who depend on dialysis or a 
kidney transplant to survive.  Kidney transplantation accounts for 57 
percent of all transplant procedures.  This statistic reflects the fact 
that many common diseases, including diabetes and glomerulonephritis (a 
heterogeneous group of immunological diseases), result in end-stage 
renal disease (ESRD), for which transplantation is the preferred 
treatment.  

Unfortunately, chronic allograft dysfunction is the most common cause of 
ESRD beyond the post-transplantation periods, accounting for 25-30 
percent of patients awaiting re-transplantation.  While the exact 
mechanism(s) responsible for chronic renal allograft failure remain 
obscure, it is generally agreed that both alloantigen-dependent and 
alloantigen-independent factors influence chronic allograft nephropathy. 
These immune-mediated attacks often result in chronic allograft 
nephropathy (CAN)   and are characterized by obliterative vasculopathy, 
glomerulosclerosis, and interstitial fibrosis.  One of the major 
hypotheses for the etiology of CAN argues that destruction of the donor 
tissue arises due to a response from the recipient's allo-immune 
response to nonself antigens.  Numerous immune cell types, 
immunoregulatory molecules, and cytokines have been implicated in the 
pathologic processes associated with CAN.  Advanced studies are needed 
to define the: relative contributions of the humoral and cellular based 
immune systems in CAN; mechanisms responsible of the pathogenesis of 
chronic dysfunction in solid renal grafts; and, approaches to better 
diagnosis, management and treatment of CAN.

Lung

Lung transplantation is a viable therapeutic option and its use has 
increased since the first successful operations in the early 1980s.  
Most lung transplantations are performed for four major disease 
processes: chronic obstructive lung disease (COPD), cystic fibrosis 
(CF), idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension 
(PH).  As a result of improvements in surgical techniques, 
immunosuppression and postoperative management, the one-year survival 
rate is approximately 80 percent.  In 50 percent of long-term lung 
transplant recipients, chronic lung allograft rejection manifests as 
bonchiolitis obliterans (OB), a complication involving scar formation 
and fibrosis in small airways accompanied by intimal thickening and 
sclerosis of vessels (chronic vascular rejection).  Studies are 
necessary to identify and characterize the events that initiate and 
maintain repetitive injury to endothelium or epithelium that is followed 
by repair and proliferation of smooth muscle cells or fibroblasts, 
leading to development of fibrotic obstructive lesions.  Further, 
studies focused on antigen-dependent processes, influenced by early 
immunologic events such as acute rejection and continuing host allo-
responsiveness, or alloantigen-independent processes, such as prolonged 
ischemia, reperfusion injury or recurrent infection, are necessary to 
understand the progressive changes that occur in chronic rejection and 
the pathogenesis of OB.
  
SPECIAL REQUIREMENTS

Applications should emphasize: collaborative research between basic 
scientists and clinical investigators; the use of new and innovative 
approaches to enhance understanding of the immunopathogenesis of chronic 
graft rejection and the clinical application and relevance of such 
approaches; and the use of the most up-to-date concepts and techniques. 
Applications from multi-institutional consortia are encouraged in order 
to unsure the appropriate mix of scientific and clinical interests of 
transplantation in humans within the RFA.  

For applications in heart transplantation, clinical research must be 
included in one of two ways: 1) a clinical project involving human 
patients or material from human patients; or 2) one or more clinical 
aims in each project.  The clinical project may be a clinical study or a 
mechanistic study attached to an ongoing trial. Projects that are 
descriptive only will not be acceptable. Projects may include animal 
models but only when the animal model can be definitely shown to be 
relevant to the human disease; and not in lieu of the requirement for 
either or both 1) or 2) above. 

For studies of lung transplantation, animal models are acceptable. 
However, evidence must be provided that it is a valid model of chronic 
rejection/bronchiolitis obliterans following lung transplantation.  In 
addition, the proposed applications must have at least one clinical 
project involving human patients or utilizing human cells and/or tissue.  

A single application may contain projects related to chronic rejection 
in the heart, lung and/or kidney.

Basic research and preclinical studies using laboratory animals is not 
encompassed under this solicitation for other  transplantation systems.

It is imperative that all applications focus on the immunopathogenesis 
of chronic rejection in humans.  Clinical trials evaluating the safety 
and efficacy of therapeutic regimens in humans will not be supported 
under this RFA; however, the analysis of data obtained from ongoing or 
completed clinical trials related to chronic rejection that are 
supported by public or private organization is highly encouraged.

Please note, in order to assure a strong level of commitment on the part 
of the principal investigator of each project, a minimum of 15% effort 
on the application is required.  Projects not meeting this requirement 
will be returned as non-responsive.

STUDY POPULATIONS

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups 
and their subpopulations must be included in all NIH supported 
biomedical and behavioral research projects involving human subjects, 
unless a clear and compelling rationale and justification are provided 
that inclusion is inappropriate with respect to the health of the 
subjects or the purpose of the research.  This policy results from the 
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should 
read the "NIH Guidelines for Inclusion of Women and Minorities as 
Subjects in Clinical Research," published in the Federal Register of 
March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and 
Contracts, Vol. 23, No. 11, March 18, 1994, and is available on the web 
at: http://grants.nih.gov/grants/guide/notice-files/not94-100.html
 
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age 
of 21) must be included in all human subjects research, conducted or 
supported by the NIH, unless there are scientific and ethical reasons 
not to include them.  This policy applies to all initial (Type 1) 
applications submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the Inclusion of Children as 
Participants in Research Involving Human Subjects that was published in 
the NIH Guide for Grants and Contracts, March 6, 1998, and is available 
at the following URL address: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators also may obtain copies of these policies from Lawrence 
Kerr, Ph.D. listed under INQUIRIES.  Program staff may also provide 
additional relevant information concerning the policy.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained 
within specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no 
obligation to view the Internet sites.  Reviewers are cautioned that 
their anonymity may be compromised when they directly access an Internet 
site.

LETTER OF INTENT

Prospective applicants are asked to submit by September 1, 2000 a letter 
of intent that includes a descriptive title of the proposed research, 
the name, address, and telephone number of the Principal Investigator, 
the identities of other key personnel and participating institutions, 
and the number and title of the RFA in response to which the application 
may be submitted.  Although a letter of intent is not required, is not 
binding, does not commit the sender to submit an application, and does 
not enter into the review of a subsequent application, the information 
that it contains allows NIAID staff to estimate the potential review 
workload and plan the review.

The letter of intent is to be sent to Dr. Meherotra listed under 
 INQUIRIES. 

APPLICATION PROCEDURES

Applicants for P01 grants must follow special application guidelines in 
the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-
PROJECT AWARDS (April 1999); this brochure is available via the WWW at: 
http://www.niaid.nih.gov/ncn/grants/multibron.htm

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants. Application kits are available at most 
institutional offices of sponsored research and from the Division of 
Extramural Outreach and Information Resources, National Institutes of 
Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, 
telephone (301) 710-0267, email: [email protected]. Applications are 
also available on the World Wide Web at 
http://grants.nih.gov/grants/forms.htm.

For purposes of identification and processing, item 2a on the face page 
of the application must be marked "YES" and the RFA number  AI-00-013  
and the words "IMMUNOPATHOGENESIS OF CHRONIC REJECTION" must be typed 
in.

The RFA label and line 2 of the application should both indicate the RFA 
number.  The RFA label must be affixed to the bottom of the face page.  
Failure to use this label could result in delayed processing of the 
application such that it may not reach the review committee in time for 
review.

The sample RFA label available at:  
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf
has been modified to allow for this change.  Please note this is in pdf 
format.

Applications must be received by October 23, 2000.  Applications that 
are not received as a single package on the receipt date or that do not 
conform to the instructions contained in PHS 398 (rev. 4/98) Application 
Kit (as modified in, and superseded by, the NIAID BROCHURE ENTITLED 
"INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS"), will be 
judged non-responsive and will be returned to the applicant.  

It is highly recommended that the appropriate NIAID or NHBLI program 
contact be consulted before submitting the letter of intent and during 
the early stages of preparation of the application.  (See program 
contact under INQUIRIES).

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed, exact, single-sided photocopies, in one 
package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express mail or courier service)

At the time of submission, two additional exact copies of the grant 
application and all five sets of any appendix material must be sent to 
Dr. Meherotra listed under  INQUIRIES. 

Concurrent submission of an R01 and a Component Project of a Multi-
project Application:  Current NIH policy permits a component research 
project of a multi-project grant application to be concurrently 
submitted as a traditional individual research project (R01) 
application.  If, following review, both the multi-project application 
and the R01 application are found to be in the fundable range, the 
investigator must relinquish the R01 and will not have the option to 
withdraw from the multi-project grant.  This is an NIH policy intended 
to preserve the scientific integrity of a multi-project grant, which may 
be seriously compromised if a strong component project(s) is removed 
from the program.  Investigators wishing to participate in a multi-
project grant must be aware of this policy before making a commitment to 
the Principal Investigator and awarding institution.

Applicants from institutions that have a General Clinical Research 
Center (GCRC) funded by the NIH National Center for Research Resources 
may wish to identify the GCRC as a resource for conducting the proposed 
research.  If so, a letter of agreement from either the GCRC program 
director or principal investigator could be included with the 
application.

SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS 
RFA

Applicants for P01 grants must follow special application guidelines in 
the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-
PROJECT AWARDS (April 1999); this brochure is available via the WWW at:
http://www.niaid.nih.gov/ncn/grants/multibron.htm

The brochure presents specific instructions for sections of the PHS 398 
(rev. 4/98) application form that should be completed differently than 
usual.  For all other items in the application, follow the usual 
instructions in the PHS 398.

REVIEW CONSIDERATIONS

Review Procedures

Upon receipt, applications will be reviewed for completeness by the NIH 
Center for Scientific Review and for responsiveness by NIAID staff.  
Incomplete and/or non-responsive applications will be returned to the 
applicant without further consideration.

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by the Division of Extramural Activities, NIAID in 
accordance with the review criteria stated below. As part of the initial 
merit review, all applications will receive a written critique and 
undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications 
under review, will be discussed, assigned a priority score, and receive 
a second level review by the National Advisory Allergy and Infectious 
Diseases Council.

Review Criteria

The general criteria for P01 grant applications are presented in the 
NIAID brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT 
AWARDS (April 1999).  Additional review criteria specific to this RFA 
are:

Schedule

Letter of Intent Receipt Date:  September 1, 2000
Application Receipt Date:       October 23, 2000
Scientific Review Date:         February, 2001
Advisory Council Date:          June, 2001
Earliest Date of Award:         July, 2001

AWARD CRITERIA

Funding decisions will be made on the basis of scientific and technical 
merit as determined by peer review, program balance, and the 
availability of funds.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.  The 
opportunity to clarify any issues or questions from potential applicants 
is welcome.  

Requests for the NIAID brochure "INSTRUCTIONS FOR APPLICATIONS FOR 
MULTI-PROJECT AWARDS" as well as inquiries regarding programmatic 
(eligibility and research scope) issues, may be directed to:

Lawrence D. Kerr, Ph.D.
Division of Allergy, Immunology and Transplantation (DAIT)
National Institute of Allergy & Infectious Diseases (NIAID)
National Institutes of Health
6700-B Rockledge Rd., Rm. 5129
Bethesda, Maryland  20892-7640
Telephone:  (301) 496-5598  
Fax:		(301) 402-2571  
Email:	[email protected]

National Heart, Lung, and Blood Institute (NHBLI)

For chronic rejection in the heart:
Judith Massicot-Fisher, Ph. D. 
National Heart, Lung and Blood Institute 
Division of Heart and Vascular Diseases 
6701 Rockledge Drive  MSC 7940 
Bethesda, MD 20892-7940 
Telephone: (301) 435-0528
Fax: 	(301) 480-1454 
E-mail :  [email protected]

For chronic rejection in the lung(s):

Susan Garfinkel, Ph.D.
NHLBI, Division of Lung Diseases
2 Rockledge Center
6701 Rockledge Drive
Bethesda, MD  20892-7952
Telephone:  (301)435-0222 
FAX: 	(301)480-3557
E-mail: 	[email protected]

Direct inquiries regarding preparation of the application and review 
issues, and address the letter of intent to, and mail two copies of the 
application and all five sets of appendices to:

Dr. Priti Meherotra  
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases
Room (insert), MSC-7616
6700-B Rockledge Drive
Bethesda, MD  20892-7616
Telephone: (301)(435-9369)
FAX:   (301)(402-2638)
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Ms. Pamela Fleming
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2119, MSC-7614
6700-B Rockledge Drive
Bethesda, MD  20892-7614
Telephone: (301) 402-6580
FAX:	  (301) 480-3780
E-mail: [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalogue of Federal Domestic 
Assistance No. 93.855, (DAIT) and 93.837 (DHVD) and 93.838 (DLD). Awards 
are made under authorization of Sections 301 and 405 of the Public 
Health Service Act, as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR 
Parts 74 and 92.  This program is not subject to the intergovernmental 
review requirements of Executive Order 12372 or Health Systems Agency 
review.

The Public Health Service strongly encourages all grant and contract 
recipients to provide a smoke-free workplace and promote the non-use of 
all tobacco products. In addition, Public Law 103-227, the Pro-Children 
Act of 1994, prohibits smoking in certain facilities (or, in some cases, 
any portion of a facility) in which regular or routine education, 
library, day care, health care or early childhood development services 
are provided to children.  This is consistent with the PHS mission to 
protect and advance the physical and mental health of the American 
people.



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