Full Text AI-93-09


NIH GUIDE, Volume 22, Number 10, March 12, 1993

RFA:  AI-93-09

P.T. 34

  Infectious Diseases/Agents 

National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  April 1, 1993
Application Receipt Date:  July 15, 1993


The Division of Allergy, Immunology and Transplantation (DAIT) of the
National Institute of Allergy and Infectious Diseases (NIAID) invites
applications for basic and preclinical studies to increase knowledge
of the host defense system in general and phagocytes in particular
and especially the application of this information to the development
of new therapies to kill infectious microorganisms.  The information
developed through this initiative would also be applicable to
intracellular localization of therapeutic agents for autoimmune and
allergic diseases.


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,
Molecular Augmentation of Host Defense, is related to the priority
areas of diabetes and chronic disabling diseases, and to immunization
and infectious diseases.  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 202-782-3238).


Research grant applications may be submitted by domestic and foreign,
for-profit and non-profit organizations, public and private
institutions, such as universities, colleges, hospitals,
laboratories, units of State and local governments, and eligible
agencies of the Federal government.  However, only domestic
organizations are eligible to apply for Program Project (P01) grants.
Applications from minority individuals and women are encouraged.


The mechanisms of support will be the individual research project
grant (R01) and the Program Project (P01) grant.  Multidisciplinary
approaches that involve collaborative efforts among investigators in
the fields of basic immunology, molecular biology, cell biology,
biochemistry, infectious disease and allergy are strongly encouraged.

The total project period for applications submitted in response to
this RFA may not exceed five years.  At this time, the NIAID is
administratively limiting the duration of P01 grants to four years;
this administrative limitation may change in the future.  P01
applications should not request budgets in excess of $500,000, and
R01 applications, $180,000, total direct costs in the first year;
neither type of application should request more than 4 percent annual
inflationary increases for future years.  An application with a first
year requested amount in excess of the above will require written
approval by senior NIAID officials via the program officer for
acceptance of the application for processing.


The estimated total funds (direct and indirect costs) available for
the first year of support for this RFA will be $1,500,000.  In fiscal
year 1994, the NIAID plans to fund approximately 10 research
projects, either as R01s or as components of P01s.  The usual PHS
policies governing grants administration and management will apply.
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 NIAID, 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.



Drug-resistant infectious agents are an increasingly important
medical problem.  Examples of drug-resistant microorganisms include
those that cause gonorrhea, tuberculosis, malaria and rheumatic
fever.  Infectious agents employ a variety of tactics to avoid the
effects of antibiotics and the strategies of the host defense system.
The objective of this RFA is to facilitate the application of
advances in our understanding of such areas as membrane receptor
trafficking, membrane fusion, and molecular transport between
cellular compartments to the development of new types of therapeutics
to combat infectious agents.  An example of such an approach would be
to deliver therapeutic agents to the intracellular compartments of
phagocytes (endosomes), that contain microorganisms using targeting
molecules that bind with high affinity to receptors that traffic
between the surface membrane and endosomes.  The ability to deliver
therapeutic agents to the appropriate site confers enormous
advantages by simultaneously increasing efficacy and diminishing
toxicity, allowing the use of substances that might otherwise be too

Research Objectives and Scope

The goal of this initiative is increased knowledge of the cell and
molecular biology of phagocytes and the use of this knowledge to
develop new forms of anti-infective agents.  Studies that involve
human tissues and cells are especially encouraged.  Examples of
relevant research topics are given below; however, these examples are
not intended to be inclusive or limiting.

o  Enhanced uptake of therapeutic agents into endosomal compartments
by such means as modification of membrane receptors, selective
regulation of expression of membrane receptors, or creation of
targeting ligands.

o  Modification of membrane receptors or their expression in order to
prevent or promote uptake of pathogens.

o  Characterization and modification of the molecules which regulate
intracellular movement of microorganisms.

o  Promotion of selective accumulation of antibiotics in various
cellular compartments including the cytosol.

o  Characterization of the intracellular fusion machine which
operates in lysosome-phagosome fusion and the mechanism(s) used by
certain organisms to disrupt this process.



NIH policy requires that applicants for NIH clinical research grants
and cooperative agreements include minorities and women in study
populations so that research findings can be of benefit to all
persons at risk of the disease, disorder or condition under study;
special emphasis must be placed on the need for inclusion of
minorities and women in studies of diseases, disorders and conditions
which disproportionately affect them.  This policy is intended to
apply to males and females of all ages.  If women or minorities are
excluded or inadequately represented in clinical research,
particularly in proposed population-based studies, a clear compelling
rationale MUST be provided.

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group, together with a rationale
for its choice.  In addition, gender and racial/ethnic issues should
be addressed in developing a research design and sample size
appropriate for the scientific objectives of the study.  This
information should be included in the form PHS 398 in items 1-4 of
the Research Plan AND summarized in item 5, Human Subjects.

Applicants are urged to assess carefully the feasibility of including
the broadest possible representation of minority groups.  However,
NIH recognizes that it may not be feasible or appropriate in all
research projects to include representation of the full array of
United States racial/ethnic minority populations [i.e., Native
Americans (including American Indians or Alaskan Natives),
Asian/Pacific Islanders, Blacks, Hispanics].  The rationale for
studies on single minority population groups should be provided.

For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, (and
preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to, clinical

The usual NIH policies concerning research on human subjects also
apply. Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.  However,
clinical samples which may be coded for use by the applicant but
could be identified by another source are not excluded.  Every effort
should be made and documented to include human tissues from women and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the U.S. populations, including minorities.

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the
selected study population is inadequate, it will be considered a
scientific weakness or deficiency in the study design and will be
reflected in assigning the priority score to the application.

All applications for clinical research submitted to NIH are required
to address these policies.  NIH funding components will not award
grants or cooperative agreements that do not comply with these

Previous recruitment data for similar studies from the proposed sites
should be provided.


Prospective applicants are asked to submit, by April 1, 1993, 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 RFA.  For
P01 grant applications, prospective applicants are also asked to
submit a list of the key investigators and their institution(s).
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 NIAID 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. Olivia Preble at the address listed under


In preparing the application in response to this RFA, the applicant
should bear in mind the research objectives of this RFA.  An R01
application should be prepared according to the instructions in form
PHS 398 (rev. 9/91).  A P01 application should be prepared using the
guidance and instructions provided in the NIAID document "SPECIAL
PROJECTS."  This document cannot be transmitted electronically,
particularly Tables I-IV which may be used by the applicant for
appropriate and consistent presentation of summary information on
budgets and personnel.  The P01 applicant should request and obtain a
copy of such document and a copy of the NIAID Information Brochure
for Program Projects and Grants, both of which may be sent along with
the RFA.  Failure to follow the instructions in the document may
result in delays in the review or in an incomplete application.

Applications are to be submitted on the standard research grant
application form PHS 398 (rev. 09/91).  For purposes of
identification and processing, item 2a on the face page of the
application must be marked "yes" and the RFA number and the words

These application forms may be obtained from the institution's office
of sponsored research or its equivalent and from the Office of Grants
Inquiries, Division of Research Grants, National Institutes of
Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone
(301) 496-7441.

Applications must be received by July 15, 1993.  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. 09/91)
application kit, will be judged non-responsive and will be returned
to the applicant.

The RFA label available in the application form PHS 398 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.

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

Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, two additional exact copies of the grant
application must also be sent to Dr. Olivia Preble at the address
listed under INQUIRIES.

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.


Upon receipt, applications will be reviewed for completeness by the
NIH Division of Research Grants (DRG) and for responsiveness by NIAID
staff; those judged to be incomplete will be returned to the
applicant without review.  Those considered to be non-responsive will
be either returned without review or, if R01s, be referred to the DRG
as unsolicited applications, to be scheduled for initial review at
the next DRG review cycle.

Those applications that are complete and responsive may be subjected
to a triage by an NIAID peer review group to determine their
scientific merit relative to other applications received in response
to this RFA.  The NIAID will withdraw from competition those
applications judged to be non-competitive for award and will notify
the applicant and institutional business officials.

Those applications judged to be competitive for award will be further
reviewed for scientific and technical merit by a review committee
convened by the Division of Extramural Activities, NIAID.  The second
level of review will be provided by the National Advisory Allergy and
Infectious Diseases Council.

The factors to be considered in the evaluation of scientific merit of
each application will be those used in the review of traditional
research project grant applications, including:  the novelty,
originality, and feasibility of the approach; the training,
experience, and research competence of the investigator(s); the
adequacy of the experimental design; and the adequacy and suitability
of the facilities.  For program project applications, additional
review criteria are used, which are outlined in the NIAID Information
Brochure on Program Project and Center Grants.  Applicants planning a
program project application may request and obtain the NIAID
Information Brochure from program staff listed under INQUIRIES.

While the following review factors do not usually influence the
priority score, they are nonetheless carefully considered by the
initial review group: the appropriateness of the requested budget to
the work proposed; the adequacy of protection of human subjects
and/or animals in research; and the adherence, whenever appropriate,
to NIH guidelines concerning adequate representation of women and
minorities in clinical research.  Any documented concerns expressed
by the initial review group about any of these factors on an
application may influence the recommendation of the Advisory Council
concerning funding of that application.


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


Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.  For P01 applicants, copies of the Information
Brochure and the documents referred to in APPLICATION PROCEDURES must
be requested.)

Direct as inquiries regarding programmatic issues to:

Howard B. Dickler, M.D.
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4A19
Bethesda, MD  20892
Telephone:  (301) 496-7104
FAX:  (301) 402-2571

Direct inquiries regarding review issues (including the preparation
of a program project application if applicable); address the letter
of intent to; and mail two copies of the application and all five
sets of appendices to:

Olivia Preble, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C20
Bethesda, MD  20892
Telephone:  (301) 496-8208
FAX:  (301) 402-2638

Direct inquiries regarding fiscal matters to:

Mr. Jeffrey Carow
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B29
Bethesda, MD  20892
Telephone:  (301) 496-7075

The mailing address given for NIAID staff in the Solar Building is
the central mailing address for NIH.  Applicants who use express mail
or a courier service are advised to follow the carrier's requirements
for showing a street address.  The address for the Solar Building is:

6003 Executive Boulevard
Rockville, MD  20852


Letter of Intent Receipt Date:  April 1, 1993
Application Receipt Date:       July 15, 1993
Scientific Review Date:         October 1993
Advisory Council Date:          February 1994
Earliest Award Date:            April 1994


This program is described in the Catalog of Federal Domestic
Assistance, No. 93.855 - Immunology, Allergy and Transplantation
Research.  Awards will be made under the authority of the Public
Health Service Act, Title III, Section 301 (Public Law 78-410, as
amended; 42 USC 241) and administered under PHS grants policies and
Federal Regulations 42 CFR Part 74.  This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.


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