NIH Guide: IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS


IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS

NIH GUIDE, Volume 22, Number 28, August 6, 1993



RFA AVAILABLE:  AI-93-012



P.T. 34



Keywords:

  AIDS 

  Immunology 

  Immune System 

  Antivirals 

  Gene Therapy+ 



National Institute of Allergy and Infectious Diseases

National Institute of Diabetes and Digestive and Kidney Diseases



Letter of Intent Receipt Date:  October 27, 1993

Application Receipt Date:  December 8, 1993



THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA);

IT IS ONLY AN ABSTRACT OF THE RFA.  POTENTIAL APPLICANTS MUST REQUEST

THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE

PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN

"INQUIRIES," BELOW.  FAILURE TO FOLLOW THE INSTRUCTIONS IN THE

COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE

RETURNED TO THE APPLICANT WITHOUT REVIEW.



PURPOSE



The National Institute of Allergy and Infectious Diseases (NIAID) and

the National Institute of Diabetes and Digestive and Kidney Diseases

(NIDDK) wish to promote research on interactions of the Human

Immunodeficiency Virus-1 (HIV-1) with the immune system that may

impact on the immunologic reconstitution of infected individuals;

cytokines to facilitate stem cell reconstitution of HIV-infected

individuals or ameliorate/reverse HIV-related damage to the immune

system; and gene-based strategies to counteract detrimental effects

of HIV-1 on the immune system, to prevent infection of stem cells

transplanted into HIV-infected individuals, and to improve the

characteristics of ex vivo expanded lymphocytes to enable them to

function more effectively in vivo.  Although clinical trials will not

be supported under this RFA, the basic and preclinical research

accomplished is expected to lay the foundation for future clinical

trials.



The NIAID and NIDDK request the coordinated submission of related

individual research project grant applications from investigators who

wish to collaborate on research, but do not require extensive shared

physical resources.  These applications must share a common theme and

describe the objectives and scientific importance of the interchange

of ideas, data, and materials among the collaborating investigators.

This collaborative research will be supported by investigator-

initiated Interactive Research Project Grant (IRPG).  For further

information, potential applicants should refer to Special

Instructions for Preparing Applications for Interactive Research

Project Grants, which may be obtained from the program staff listed

under INQUIRIES.



HEALTHY PEOPLE 2000



The Public Health Service (PHS) is committed to achieving the health

promotion and disease prevention objectives of "Healthy People 2000,"

a PHS-led national activity for setting priority areas.  This RFA,

Immune Reconstitution of HIV-Infected Individuals, is related to the

priority area of HIV infection.  Potential applicants may obtain a

copy of "Healthy People 2000" (Full Report:  Stock No.

017-001-00474-0) or "Healthy People 2000" (Summary Report:  Stock No.

017-001-00473-1) through the Superintendent of Documents, Government

Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by domestic and foreign, 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.

Applications from minority individuals and women are encouraged.



MECHANISM OF SUPPORT



The support mechanism for this program will be individual research

project grants (R01s) which are organized around a common theme into

an IRPG.  It is the responsibility of the applicants to plan, direct

and execute the proposed projects in accord with their interests and

perceptions of potential treatment strategies utilizing immune

reconstitution.  The total project period for applications submitted

in response to the present RFA may not exceed four years.  IRPG

applications considered responsive to this RFA will have at least two

components, one proposing research on stem cell or somatic cell

therapies and one proposing gene-based therapeutic strategies.

Reissuance of this initiative in future years is anticipated but not

certain.



FUNDS AVAILABLE



The NIAID and NIDDK anticipate awarding two to four IRPGs (a total of

six to eight R01 awards), for a total cost of $1.9 million for the

initial year of funding.  The NIAID has set aside $1.2 million for

applications received in response to this RFA, and the NIDDK has set

aside $0.7 million for this purpose.



RESEARCH OBJECTIVES



The long term goal of this RFA is to provide an experimental basis

for using immune reconstitution as a therapy in individuals whose

immune systems are compromised by infectious disease.  This RFA

focuses on HIV/AIDS.



Research responsive to this RFA includes, but is not limited to, the

following:



o  Research to clarify interactions of HIV with the immune system

that may bear on the successful reconstitution of infected

individuals and gene-based strategies to counter HIV-related damage

to the immune system;



o  Research on antiviral strategies, including the design and

evaluation of new gene-based antiviral strategies to be used in stem

cells or other sources of immune cells;



o  Research to discover and/or develop novel sources of multipotent

stem cells that can be genetically engineered to resist HIV-1

infection, new cytokines capable of interacting with T cell

progenitor cells or their immediate antecedents, new assays to

quantitate T cell progenitor cells.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN

CLINICAL RESEARCH STUDY POPULATIONS



For projects involving clinical research, NIH requires applicants to

give special attention to the inclusion of minorities and women in

study populations.  If women and minorities are not included in the

study populations for clinical studies, a specific justification for

this exclusion must be provided.  Applications without such

documentation will not be accepted for review.



LETTER OF INTENT



Prospective applicants are asked to submit, by October 27, 1993, a

letter of intent that includes descriptive titles of each proposed

research project in the IRPG group, the names and address of the

Principal Investigators and other key personnel, the participating

institutions, and the number and title of this RFA.  Although a

letter of intent is not required, is not binding, and does not enter

into the review of subsequent applications, the information that it

contains allows the NIAID and NIDDK to estimate the potential

workload for reviewers and to avoid possible conflict of interest in

the review process.  The letter of intent is to be sent to Dr. Dianne

Tingley at the address indicated in INQUIRIES below.



APPLICATION PROCEDURES



The research grant application form PHS 398 (rev. 9/91) is to be used

in applying for these grants.  This form is available at most

institutional offices of sponsored research and from the Office of

Grants Information, Division of Research Grants, National Institutes

of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone

(301) 594-7248.  Additional instructions for the preparation of

interactive project applications will be provided with the RFA.

Applications not received by December 8, 1993, will be considered

unresponsive and returned to the applicant without review.



REVIEW CONSIDERATIONS



Upon receipt, applications will be reviewed by Division of Research

Grants (DRG) for completeness and by NIAID and NIDDK staff to

determine responsiveness.  Incomplete and non-responsive applications

will be returned to the applicant without further consideration or

review.  Those applications considered responsive to the RFA may be

subjected to a triage by a peer review group, before or during the

review committee meeting, to determine their scientific merit

relative to the other applications submitted in response to this RFA.

The NIAID will remove from further competition those applications

judged to be noncompetitive for award and will notify the applicant

and the institutional business official.



Those applications judged to be competitive for award will be further

reviewed for scientific and technical merit by an appropriate review

committee convened by the Division of Extramural Activities, NIAID.

A second level of review will be provided by the NIAID and NIDDK

Councils.  Factors to be considered in the evaluation of each

application will be similar to those used in review of traditional

research grant applications and, in addition, will include those

addressing overall proposed collaboration.



INQUIRIES



Written and telephone requests for the RFA and the opportunity to

clarify any issues or questions from potential applicants are

welcome.  It is essential that prospective applicants obtain a copy

of the RFA and the Special Instructions for Preparing Applications

for IRPGs before preparing an application.  Direct requests for the

RFA and inquiries regarding scientific issues or responsiveness to:



Dr. Sandra Bridges

Developmental Therapeutics Branch

National Institute of Allergy and Infectious Diseases

Solar Building, Room 2C12

Bethesda, MD  20892

Telephone:  (301) 496-8197



Dr. Ralph Bain

Division of Kidney, Urologic, and Hematologic Diseases

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 3A05

Bethesda, MD  20892

Telephone:  (301) 594-7556



Address the letter of intent and questions regarding review of

applications to:



Dr. Dianne Tingley

Scientific Review Program

National Institute of Allergy and Infectious Diseases

Solar Building, Room 4C16

Bethesda, MD  20892

Telephone:  (301) 496-0818



Direct inquiries regarding fiscal matters to:



Ms. Jane Unsworth

Grants Management Branch

National Institute of Allergy and Infectious Diseases

Solar Building, Room 4B22

Bethesda, MD  20892

Telephone:  (301) 496-7075



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic

Assistance, 93.856 - Microbiology and Infectious Diseases Research

and 93.855 - Immunology, Allergy and Transplantation Research.

Awards are made under authorization of the Public Health Service Act,

Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158,

42 USC 241 and 285) and administered under PHS grants policies and

Federal Regulations 42 CFR Part 52 and 45 CFR Part 74.  This program

is not subject to the intergovernmental review requirements of

Executive Order 12372 or Health Systems Agency review.



.