Full Text PA-97-106
 
FELINE IMMUNODEFICIENCY VIRUS:  A POTENTIAL MODEL OF AIDS
 
NIH GUIDE, Volume 26, Number 31, September 19, 1997
 
PA NUMBER:  PA-97-106
 
P.T.


Keywords: 

 
National Institute of Allergy and Infectious Diseases
 
PURPOSE
 
The NIAID, National Institutes of Health (NIH), invites applications
on the molecular biology, immunology, and host factors involved in
feline immunodeficiency virus (FIV) infection of cats.  The overall
goal of these studies is to advance the understanding of the
virus/host infection process in this model to determine the potential
use of, and to validate the application of, the FIV/cat model for
testing potential therapeutics, topical microbicides, and novel
mucosal-targeted vaccine designs against the human immunodeficiency
virus (HIV).  Applicants proposing studies focusing solely on FIV
pathogenesis are encouraged to apply under PA-96-072 "Mechanisms of
AIDS Pathogenesis".
 
Applications submitted in response to PAs are assigned according to
established PHS referral guidelines.
 
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,
"FELINE IMMUNODEFICIENCY VIRUS:  A POTENTIAL MODEL OF AIDS", is
related to the priority area of human immunodeficiency virus (HIV)
infection.  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
202-2512-1800).
 
ELIGIBILITY
 
Applications may be submitted by 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.  Domestic and foreign
institutions are eligible to apply for R01 and R03 grants.  Foreign
institutions are not eligible for First Independent Research Support
and Transition (FIRST) awards (R29).  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.
 
MECHANISMS OF SUPPORT
 
Traditional research project grants (R01) as well as R03 and R29
applications may be submitted in response to this announcement.  The
duration of R01 grants under this PA is limited to five (5) years;
applications for R29 grants must request five (5) years of support.
 
NIAID uses R03 grants to support small, highly innovative or pilot
projects.  Applicants for R03 grants may request up to $50,000 annual
direct costs for a period not to exceed three (3) years.  Funds and
time requested should be appropriate for the research proposed.
Applicants for R03 grants must follow the special application
guidelines and Terms and Conditions of Award in the NIAID SMALL
RESEARCH GRANTS brochure (September 1996); this brochure is available
via the WWW at: http://www.niaid.nih. gov/ncn/tools/broch.htm.
 
Responsibility for the planning, direction, and execution of the
proposed research for all applicable mechanisms of support will be
solely that of the applicant.
 
RESEARCH OBJECTIVES
 
Background
 
A major problem in evaluating the effectiveness and safety of
therapeutic compounds and strategies against HIV disease is the lack
of a reproducible, reliable, and inexpensive animal model.
Currently, two models are used extensively for therapeutic
evaluation:  HIV-infected severe combined immunodeficient (SCID) mice
transplanted with human tissue, and simian immunodeficiency virus
(SIV)-infected monkeys.  However, studies in these models have
certain limitations, for example limited pathogenesis, disease, and
biological scope of the model (SCID/HIV), or lack of specific
pathogen-free animals and the expense of the model which precludes
large, statistically significant studies (SIV/monkey).  As the most
recently identified lentivirus, FIV represents a valuable but
understudied small animal model for HIV/AIDS research because:  (i)
analogous to HIV infection of human CD4 cells, FIV primarily infects
and replicates to the highest levels in CD4 lymphocytes of cats and
appears to bind to the CXC chemokine receptor;  (ii) FIV produces an
immunodeficiency disease in cats that closely mimics AIDS caused by
HIV in humans; (iii) specific pathogen-free cats are readily
available and are relatively inexpensive to purchase and maintain;
and, (iv) vaginal and rectal challenge experiments have demonstrated
the feasibility of using this model to investigate mucosal
transmission of FIV.  The FIV/cat model may thus fill an important
niche and promote a more aggressive and wider use of animal models
for identifying and optimizing promising therapeutic and preventative
candidates.  In addition to expanding the breadth of the model for
testing therapeutic and topical microbicides, the FIV/cat model could
stimulate the development of immunogens and immunization strategies
for inducing genital and gastrointestinal mucosal T- and B-cell
immunity to lentiviruses that are both critical for successful HIV
vaccine development.
 
Research Objectives and Scope
 
This program announcement is designed to stimulate research on the
molecular biology of FIV in order to develop and validate the animal
model for application in HIV studies such as testing potential
therapeutics, topical microbicides, and novel mucosal-targeted
vaccine designs for humans and optimizing current therapeutic
regimens.
 
Relevant research objectives include, but are not limited to, the
following:
 
o  Studying FIV genes and their encoded proteins;
 
o  Studying host factors that interact with FIV proteins or
regulatory sequences;
 
o  Elucidating key aspects of the biology, immunology, and sanctuary
sites of FIV infection of cats; and,
 
o  Advancing and optimizing the mucosal challenge model for testing
potential topical microbicides and vaccines.
 
These and related areas of investigation will be considered
responsive to the objectives of the PA as they are vital for in-depth
understanding of the model, its validation, and its subsequent use in
evaluating therapeutics, preventative agents, and vaccines.
 
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 sub-populations must be included as subjects in all NIH
supported biomedical and behavioral research projects involving human
subjects, unless a clear and compelling rationale and justification
is provided that inclusion is inappropriate with respect to the
health of the subjects or the purpose of the research.  This new
policy results from the NIH Revitalization Act of 1993 (Section 492B
of Public Law 103-43) and supersedes and strengthens the previous
policies (Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations) which
have been in effect since 1990.  The new policy contains some new
provisions that are substantially different from the 1990 policies.
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 reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994, Volume
23, Number 11.
 
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.
 
APPLICATION PROCEDURES
 
Applications are to be submitted on the grant application for PHS 398
(rev. 5/95) and will be accepted on the standard application
deadlines as indicated on the application kit.
 
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@odrockm1.nih.gov.
 
For purposes of identification and processing, item 2 on the face
page of the application must be marked "YES".  The PA number and the
PA title must also be typed in section 2.
 
The completed, signed original and five legible, single-sided copies
of the application must be sent or delivered to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817-7710 (for express/courier service)
 
FIRST (R29) awards  applications must include at least three sealed
letters of reference attached to the face page of the original
application.  FIRST applications submitted without the required
number of reference letters will be considered incomplete and will be
returned without review.
 
Applicants for small research (R03) grants are to follow the
application guidelines in the NIAID SMALL RESEARCH GRANTS
brochure (September 1996) which is available from the program staff
listed under INQUIRIES and via the WWW at:
http://www.niaid.nih.gov/ncn/tools/broch.htm.  R03 applications that
do not conform to the instructions in the brochure will be judged
non-responsive and returned to the applicant.
 
REVIEW CONSIDERATIONS
 
Review Procedures
 
Applications will be assigned on the basis of established PHS
referral guidelines. Upon receipt, applications will be reviewed for
completeness by the NIH Division of Research Grants.  Incomplete
applications will be returned to the applicant without further
consideration. When the subject of an application is of interest to
more than one component of NIH, dual assignments are made.
 
R01 and R29 applications will be reviewed for scientific and
technical merit by study sections of the Division of Research Grants,
NIH, in accordance with the standard NIH peer review procedures. 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
appropriate national advisory council.
 
R03 applications will be evaluated for scientific and technical merit
by an appropriate peer review group convened by the NIAID.
 
Review Criteria
 
The five criteria to be used in the evaluation of grant
applications are listed below.  To put those criteria in context, the
following information is contained in instructions to the peer
reviewers.
 
The goals of NIH-supported research are to advance our
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.  Does this study address an important problem? If
the aims of the application are achieved, how will scientific
knowledge be advanced?  What will be the effect of these studies on
the concepts or methods that drive this field?
 
2.  Approach.  Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to
the aims of the project?  Does the applicant acknowledge potential
problem areas and consider alternative tactics?
 
3.  Innovation.  Does the project employ novel concepts, approaches
or method?  Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
 
4.  Investigator.  Is the investigator appropriately trained and well
suited to carry out this work?  Is the work proposed appropriate to
the experience level of the principal investigator and other
researchers (if any)?
 
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?
Is there evidence of institutional support?
 
The initial review group will also examine: the appropriateness of
proposed project budget and duration; 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.
 
Review criteria for R03 applications are described in the
guidelines cited above.
 
The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other
favorably recommended applications.  The following will be considered
when making funding decisions: quality of the proposed project as
determined by peer review, program balance among research areas of
the announcement, and availability of funds.
 
INQUIRIES
 
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
 
Requests for the NIAID brochure "NIAID SMALL RESEARCH GRANTS" as well
as inquiries regarding programmatic (research scope, eligibility and
responsiveness) issues may be directed to:
 
Dr. Roger H. Miller
Targeted Interventions Branch
Division of AIDS, NIAID
Solar Building, Room 2C36A
6003 Executive Blvd.
Bethesda, MD 20892-7640
Telephone: (301) 496-6430
Fax:  (301) 402-3211
Email:  rm42i@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Ms. Jane Unsworth
Division of Extramural Activities, NIAID
Solar Building, Room 4B25
6003 Executive Blvd.
Bethesda, MD 20892-7610
Telephone: (301) 496-7075
Fax:  (301) 480-3780
Email: ju3a@nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is supported under authorization of the Public Health
Service Act, Sec. 301(c), Public Law 78-410, as amended.  The
Catalogue of Federal Domestic Assistance Citation is No. 93.856 -
Microbiology and Infectious Disease Research.  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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