OPPORTUNITIES IN AIDS RESEARCH GRANT PROGRAM:  HUMAN IMMUNOLOGY

Release Date:  March 17, 1998

PA NUMBER:  PAS-98-040

P.T.

Office of AIDS Research
National Institute of Allergy and Infectious Diseases
National Institute of Child Health and Human Development
National Cancer Institute
National Heart, Lung and Blood Institute
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute on Aging

Letter of Intent Receipt Date:  April 14, 1998
Application Receipt Date:  May 15, 1998

PURPOSE

This Program Announcement (PA) is a new initiative entitled "OPPORTUNITIES in
AIDS RESEARCH Grant Program:  Human Immunology" and implemented by the
National Institutes of Health (NIH) on the recommendation of the Office of
AIDS Research Advisory Council (OARAC).  This program intends to encourage
novel and innovative research in human immunology aimed at enhancing our
understanding of the behavior of the human immune system and the biology of
human lymphocyte populations.

The emphasis of this program is on supporting human immunology research
projects that are particularly innovative, novel, high risk/high impact and
show clear promise for advancing the basic understanding of the development
and functioning of the immune system needed to more rationally approach immune
reconstitution in HIV-infected subjects during infection and in the period
after introduction of effective antiviral therapy.

Applications are especially welcome from new investigators and those not
currently active in  research on the acquired immunodeficiency syndrome
(AIDS).  The OPPORTUNITIES in AIDS RESEARCH Grant Program utilizes a grant
mechanism which provides funds to projects of an exploratory nature to
generate preliminary data for further studies.  In addition, the program
utilizes streamlined review and award processes to accelerate progress in this
scientific area.  The general area of investigation targeted by this program
is the characterization of T-lymphocyte homeostasis in humans under normal
conditions, during HIV infection, or in the period after introduction of
effective antiretroviral therapy.  Special emphasis will be given to studies
aimed at developing and improving reagents and methodologies needed to enhance
our ability to study immune function and lymphocyte dynamics in humans.

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 PA, Opportunities in AIDS Research
Grant Program:  Research in Human Immunology, is related to the priority areas
of HIV infection, immunization, and infectious diseases.  Potential applicants
may obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0 or Summary Report:  Stock No.017-001-00473) through the
Superintendent of Documents, Government Printing Office, Washington, DC
20402-0325 (telephone 202-512-1800).

ELIGIBILITY

Applications may be submitted by domestic and foreign for-profit and
non-profit organizations, both public and private, such as universities,
colleges, hospitals, laboratories, units of state and local governments, and
eligible agencies of the Federal Government.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to apply as
principal investigators.

MECHANISM OF SUPPORT

Research projects will be supported with the Exploratory/Developmental
Research Grant mechanism (R21).  This mechanism provides short-duration
support for preliminary studies of a highly speculative nature that are
expected to yield, within this time frame, sufficient information upon which
to base a well-planned and rigorous series of further investigations. 
Applicants may request up to two years of support and up to $150,000 per annum
in direct costs, although with compelling justification exceptions can be made
if specific costly reagents, animals, specimens or laboratory modifications
are needed to perform these studies.

Program staff may be able to advise prospective applicants concerning
NIH-sponsored resources that may be available to them.  Contact the program
staff listed under INQUIRIES for further information.  The award is
non-renewable; however, the hope is that grantees under this program will
progress through this exploratory phase further along the research/development
pipeline; applicants may elect to seek continuing support for this research
through the R01 mechanism.

Responsibility for the planning, direction, and execution of the proposed will
be solely that of the applicant.

FUNDS AVAILABLE

The estimated total funds (direct and indirect) available for the first year
of support for this PA will be $6.0 million.  This level of support is
dependent on the receipt of a sufficient number of applications of high
scientific merit.  Although this program is provided for in the financial
plans of the Office of AIDS Research (OAR), awards pursuant to this PA 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 year(s) and the availability of
funds.  At this time, OAR has not determined whether or how this solicitation
will be continued beyond the present PA.

RESEARCH OBJECTIVES

Understanding the normal development and functioning of the human immune
system is crucial to our ability to understand the effects of the human
immunodeficiency virus (HIV) on the immune system and the pathogenesis of
AIDS.  This understanding holds the key to developing a successful vaccine to
prevent HIV infection and disease and for designing more effective therapies
to limit immune system damage and to restore functional immune responses in
HIV-infected subjects.  Progress in immunology research in the past few
decades has been built, in many instances, on a foundation of basic knowledge
derived from the study of the mouse immune system.  While important lessons
can be learned from this experimental system, not all the findings from this
model can be directly translated to the nonhuman primate and human systems
because of their intrinsic heterogeneity and complexity.  NIH intends to
promote studies that will address unresolved issues in human immunology that
hold the key to progress in important areas of AIDS research.  A greater
understanding of the human immune system is particularly needed now in the era
of antiviral combination therapies, when we can prolong the life expectancy
and quality of life of HIV-infected individuals but are confronted with issues
of immune reconstitution.  After examination of the state of the art of human
immunology as it relates to these issues, the National Institute of Allergy
and Infectious Diseases (NIAID), National Cancer Institute (NCI), National
Institute of Child Health and Human Development (NICHD), National Heart, Lung
and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK), and National Institute on Aging (NIA) and the OARAC
have identified the following general topic in human immunology research as
the scientific area targeted by this program announcement:  Characterization
of T-lymphocyte homeostasis in humans under normal conditions, during HIV
infection, and in the period after introduction of effective antiretroviral
therapy (HAART).  Special emphasis will be given to studies aimed at
developing and improving reagents and methodologies needed to enhance our
ability to study immune function and T-lymphocyte dynamics in humans.  The
areas of research listed below are not intended to be all inclusive, but are
designed to give applicants some direction regarding the research areas that
NIH is interested in stimulating:

-  Definition of the contribution of the thymus to naive T-cell homeostasis in
children, adolescents, and adults;

-  Biology of thymic involution in vivo;

-  Identification of phenotypic markers for recent thymic emigrants in the
human;

-  Characterization of factors including cytokines and chemokines required to
attract hematopoietic stem cells to the thymus and control their
differentiation within the thymus;

-  Naive T-cell development and life span, in the presence or absence of a
functional thymus;

-  Homeostasis of naive T-cells.  Characterization of factors that determine
the development, maintenance, and functional regulation of these cells;

-  Characterization of the postulated microenvironmental niches required for
T-cell subset homeostasis in vivo and of T-cell homing and recirculation;

-  Quantitative/qualitative analysis of human memory/effector T-cell
differentiation from naive T-cell in vivo;

-  Life span and homeostasis of memory T-cell populations and characterization
of factors that determine the maintenance, peripheral expansion, and
functional regulation of these cells; and

-  Homeostasis, trafficking and immune responses of cells comprising the
mucosal lymphoid follicles that line the gastrointestinal tract forming the
Gut Associated Lymphoreticular Tissue.

To help meet the research objectives defined by NIAID, NCI, NICHD, NHLBI,
NIDDK, NIA and the OARAC, research applications intended to produce
preliminary data or precedent for an idea or a concept are particularly
encouraged.

SPECIAL REQUIREMENTS

Awardees will be expected to attend a meeting to showcase the progress of the
work funded under this program.  Details of this meeting will be provided
post-award.  Thus, applicants should include in their budget request funds for
the PI to attend one meeting in the Washington, DC area.

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 of 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," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and the NIH Guide for Grants and Contracts, Vol. 23, No.
11, March 18, 1994.

Investigators may obtain copies from these sources or from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by April 14, 1998, a letter of
intent that includes a descriptive title of the overall proposed research; the
name, address, and telephone number of the Principal Investigator; and the
number and title of this PA.  Although the 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 subsequent applications, the information that it
contains allows NIH staff to estimate the potential review workload and to
avoid conflict of interest in the review.  The letter of intent is to be sent
to Dr. Fulvia Veronese at the address listed under INQUIRIES.

APPLICATION PROCEDURES

Applications are to be submitted on form PHS 398 (rev. 5/95), the standard
application form for research grants.  Application kits are available at most
institutional offices of sponsored research and may be obtained 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:  ASKNIH@od.nih.gov.  Application kits also may be
obtained electronically via the WWW at
http://www.nih.gov/grants/funding/phs398/phs398.html.  Applicants must adhere
to the format and requirements specified in the PHS 398 application kit (rev.
5/95), except as noted below.

For purposes of identification and processing the application, mark "YES" in
item 2 on the face page and enter the PA number PAS-98-040 and the title
"OPPORTUNITIES in AIDS RESEARCH Grant Program:  Human Immunology."

Applicants are encouraged to identify the research area(s) under the RESEARCH
OBJECTIVES and to describe very briefly in the cover letter how their proposed
research relates to the general scientific area targeted by this PA.

The research plan will be strictly limited to 10 pages total.  Appendices may
not be used to circumvent the page limitations of this PA.  Applications that
exceed the page limit will be returned without review.  Amended applications
will not be accepted under any circumstances.  Late or incomplete applications
will not be accepted and will be returned.

No additional materials pertaining to a particular application will be
accepted after the receipt date for which the application is submitted except
for certifications of Institutional Review Board (IRB) or Institutional Animal
Care and Use Committee (IACUC) approval.  As specified in the PHS 398 form,
certifications of IRB or IACUC approval must be received within 60 days after
the receipt date for which the application is submitted.

A modular budget application format will be used, in which budgets and
justifications are simplified.  Applicants may apply for up to two years of
support at up to $150,000 direct cost per annum, and total direct costs may be
requested in modular increments of  $10,000.  The form, "Detailed Budget for
Initial Budget Period" (page 4 of the PHS 398 application kit, rev. 5/95), IS
NOT TO BE USED and will NOT be accepted at the time of application. 
Applicants are to use the form, "Budget for Entire Proposed Period of Support"
(page 5 of the PHS 398 application kit, rev. 5/95), leaving blank the
categorical budget table and providing only the requested total direct costs
for each year and total direct costs for the entire proposed period of
support.  All project personnel (salaried or unsalaried) should be listed by
name, role on project, and percent effort.  A narrative justification is to be
provided for each person based on his/her role on the project and proposed
level of effort, and biosketches are to be provided for key personnel.  All
consultants should be identified by name and organizational affiliation, and
the services they will perform should be described.  A narrative justification
should be provided for any major budget item(s), other than personnel, which
would be considered unusual for the scope of research; otherwise, no specific
costs for items or categories should be shown.  Applications exceeding
$150,000 in requested total direct costs also will require a special narrative
justification, identifying the required specific costly reagents, animals,
specimens, or laboratory modifications which are required.

The budget justification should begin in the space provided, using
continuation pages as necessary, and should justify the requested budget on
the basis of overall requirements, scientific aims, and scope of the proposed
research.  If consortium/contractual costs are requested, the percentage of
the subcontract total costs (direct and indirect) relative to the total direct
cost of the overall project should be specified.

Note the Special Requirements section of this PA for specific travel budget
information.

All applications must include the completed Checklist (Form Page II) of the
PHS 398 grant application kit (rev. 5/95)

The completed, signed original and four legible, single-sided copies of the
application must be sent or delivered 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/courier service)

At the time of submission, one additional exact copy of the grant application
must be sent to Dr. Fulvia Veronese at the address listed under INQUIRIES.

REVIEW CONSIDERATIONS

Review Procedures

Upon receipt, applications will be reviewed for completeness by the Center for
Scientific Review (CSR) and for responsiveness to the goals of the PA by the
participating Institutes.  Incomplete and/or nonresponsive applications will
be returned to the applicant without further consideration.  Applications will
be evaluated for scientific and technical merit by appropriately constituted
Scientific Peer Review Group(s) (SPRG) convened by the CSR, in accordance with
standard NIH review policies.  As part of the initial merit review, all
applications may undergo a process in which only those applications deemed to
have the highest scientific merit will be assigned a priority score and
receive a second level review by the appropriate national advisory council.

Review Emphasis

The major review emphasis will be placed on the overall concept of the
proposed work and the level of potential impact on advancing the understanding
of human immunology.

The major goal of the OPPORTUNITIES in AIDS RESEARCH Grant Program is to
foster  relatively unexplored human immunology research as it relates to the
development of potential immune reconstitution approaches in HIV-infected
subjects.  As such, review of these applications is not dependent on the
submission of comprehensive preliminary data; however, sufficient data should
be presented to justify the exploratory study.

As noted earlier in this program announcement, new investigators and newcomers
to this field are especially encouraged to apply.  Prior experience in HIV
research is not considered a necessary criterion for evaluating an applicant's
abilities or capability of performing the proposed work.  Furthermore, the
proposed work need not include studies on HIV/AIDS.

Review Criteria

The five criteria to be used in the evaluation of these grant applications are
listed below.  To put these criteria in context, the following information is
contained in instructions to the peer reviewers.

The goals of NIH-supported research are to advance the understanding of
biological systems, improve the control of disease, and enhance health.  The
reviewers will comment on the following aspects of the application in their
written critiques in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered by the reviewers in assigning the
overall score, weighting them as appropriate for each application.  Note that
the application does not need to be strong in all categories to be judged
likely to have a major scientific impact and thus deserve a high priority
score.  For example, an investigator may propose to carry out important work
that by its nature is not innovative but is essential to move a field forward.

1.  Significance.  If successful, will the proposed work advance our goal of a
better understanding of human immunology as it relates to immune
reconstitution?  Is it likely the proposed work will advance the particular
scientific area it targets?

2.  Innovation.  Are the proposed aims particularly novel and worthy of
exploratory study?  Does the project employ novel concepts, approaches or
method?  Does the project challenge existing paradigms or develop new
methodologies or technologies?

3.  Approach.  Are the methods, subjects and materials appropriate to
accomplish the goals of the proposed work?

4.  Investigator.  Considering their respective backgrounds and proposed
roles, are the proposed personnel qualified to perform the study?

5.  Environment.  Does the scientific environment in which the work will be
done contribute to the probability of success?  Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements?

The initial review group also will examine:  the appropriateness of proposed
project budget; the adequacy of plans to include both genders and minorities
and their subgroups as appropriate for the scientific goals of the research
and plans for the recruitment and retention of subjects; the provisions for
the protection of human and animal subjects; and the safety of the research
environment.

AWARD CRITERIA

The following will be considered in making funding decisions:  the scientific
and technical merit of the proposed project as determined by peer review, and
the availability of funds.  In the final selection of applications to be
funded, consideration will be given to achieving balanced coverage of the
scientific areas of emphasis recommended by the participating Institutes.

INQUIRIES

Inquiries regarding the program announcement are strongly encouraged.  The
opportunity to clarify any issues or questions from potential applicants is
welcome.  Additional information can be retrieved from the relevant ICD
Internet Web sites, which can be accessed through the NIH home page:
www.nih.gov.

Applicants new to the field of AIDS research are encouraged to explore the NIH
AIDS Research and Reference Reagent Program and the availability of human
specimens at http://www.niaid.nih.gov/reposit/default.htm.  These programs
make available small quantities of viruses, antibodies, HIV proteins,
plasmids, and other reagents to researchers.

Direct inquiries regarding programmatic issues to:

Dr. Fulvia Veronese
Office of AIDS Research
National Institutes of Health
Bethesda, MD  20892
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-3677
FAX:  (301) 496-4843
Email:  fv10x@nih.gov

Dr. Helen Quill
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4A22
Bethesda, MD  20892-7640
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-7551
FAX:  (301) 402-2571
Email:  hq@nih.gov

Dr. Allan Lock
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B01, MSC-7510
Bethesda, MD  20892-5710
Telephone:  (301) 496-5541
FAX:  (301) 402-4083
Email:  al39o@nih.gov

Dr. John F. Finerty
Cancer Immunology Branch
National Cancer Institute
6130 Executive Boulevard, Room 513
Rockville, MD  20852
Telephone:  (301) 496-7815
FAX:  (301) 402-1037
Email:  fin@nih.gov

Dr. LeeAnn Jensen
Division of Blood Diseases and Resources
National Heart, Lung and Blood Institute
6701 Rockledge Drive, Room 10140 - MSC 7950
Bethesda, MD  20892-7950
Telephone:  (301) 435-0065
FAX:  (301) 480-1060
Email:  jensonl@gwgate.nhlbi.nih.gov

Dr. David G. Badman
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-13C, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-7717
FAX:  (301) 480-3510
Email:  David_Badman@nih.gov

Dr. Anna M. McCormick
Biology of Aging Program
National Institute on Aging
Gateway Building, Suite 2C231
Bethesda, MD  20892
Bethesda, MD  20814 (for express/courier service)
Telephone:  (301) 496-6402
FAX:  (301) 402-0010
Email:  am38k@nih.gov

Direct inquiries regarding review matters to:

Dr. Jean Paddock
Division of Clinical and Population-Based Studies
Center for Scientific Review
6701 Rockledge Drive, Room 5100
Bethesda, MD  20817
Telephone:  (301) 435-1163
FAX:  (301) 480-2241
Email:  paddockj@drg.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Mary Kirker
Grants Management Branch
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B23
Bethesda, MD  20892-7640
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 402-6400
Email:  mk35h@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.855 and 93.856 (NIAID).  Awards are made under authorization of the Public
Health Service Act, Sec. 301(c), Public Law 78-410, as amended.  Awards will
be 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 review.

The PHS 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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