Full Text AI-93-015

IMMUNOLOGIC INTERVENTION IN PARASITIC DISEASES

NIH Guide, Volume 22, Number 17, April 30, 1993

RFA:  AI-93-015

P.T. 34

Keywords: 
  Immunotherapy 
  Pathogenesis 
  Parasitology 


National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  June 15, 1993
Application Receipt Date:  July 22, 1993

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID)
invites applications for innovative preclinical and clinical research,
in relevant animal models and human subjects, to identify and
accelerate development of novel therapeutic interventions based on
targeted disruption of the contributions of cytokines to pathogenesis
in parasitic diseases.

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 Request
for Applications (RFA), Immunologic Intervention in Parasitic Diseases,
is related to the priority area of 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 202-783-3238).

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.
Successful applications from foreign institutions, however, are limited
to three years of support without indirect costs. Applications from
minority individuals and women are encouraged.

MECHANISM OF SUPPORT

Awards made under this RFA will use the National Institutes of Health
(NIH) individual research project grant (R01).  Responsibility for the
planning, direction, and execution of the proposed project will be
solely that of the applicant.  The total project period for
applications submitted by domestic institutions in response to the
present RFA may not exceed four years.  The total project period for
applications submitted by foreign institutions may not exceed three
years.  The anticipated earliest possible award date is April 1, 1994.

Applicants are encouraged to coordinate, through the use of consortium
arrangements or subcontracts, integrated approaches with individuals or
institutions having relevant reagents and expertise in their use,
demonstrated ability in a particular area of relevant research, or
access to relevant patient populations so as to accelerate technical
progress and clinical development of promising therapies.  Because the
nature and scope of the research proposed in response to this RFA may
vary, it is anticipated that the amount of each award will vary also.

This RFA is a one-time solicitation.  Future competing continuation
applications will compete with all unsolicited investigator-initiated
applications and be reviewed by an appropriate Study Section according
to the customary NIH referral and peer review procedures.

FUNDS AVAILABLE

The estimated level of support (total direct and indirect costs) for
the entire program for the first year is $ 1.8 million.  Foreign
applications that may be funded under this RFA are not eligible for
indirect costs.  The NIAID anticipates making a minimum of three new
awards.

RESEARCH OBJECTIVES

Background

Diseases caused by protozoan and helminth parasites plague billions of
people worldwide, killing millions annually and inflicting irreversible
debilitating injuries, such as blindness and disfiguration, on
additional millions. Globally their economic impact is enormous, and is
often cited as a key impediment to further social and economic progress
in developing nations.  Due to changing ecological patterns and
development of resistance to previous methods of control, the magnitude
of many parasitic diseases in endemic areas is increasing.  Many of
these diseases are of increasing international concern as tourism,
trade, business travel, immigration and military activities extend
their impact into industrialized countries.  In addition, latent
parasitic infections evolving to produce acute diseases have been noted
with the increased prevalence of immunodeficiency states and the use of
immunosuppression in medical therapy.  Finally, current therapies for
many of the parasitic diseases are inadequate, poorly tolerated or
ineffective.  New therapeutic and prophylactic interventions against
parasitic diseases are urgently needed.

In a wide variety of infectious diseases untoward immune responses lead
to pathology rather than protection.  It has already been shown that
cytokines are associated with immunopathology in several infections of
parasitic etiology, such as cutaneous leishmaniasis, South American
trypanosomiasis, schistosomiasis, and malaria.  Whether or not a
pathogenic or protective immune response is elicited often depends on
which T lymphocyte subsets (i.e., Th1 or Th2) dominate the response to
infection and elaborate characteristic cytokines.  These observations
indicate the need for a systematic and focused analysis of the
relationship between cytokine effects and parasitic disease, with the
aim of developing new therapeutic strategies for intervention.  Such
studies will contribute information beneficial not only for the control
of human parasitic diseases, but also for the control of other
infectious diseases with immunopathologic components.

Scope of Research

The purpose of this RFA is to stimulate innovative new research to
investigate novel therapeutic interventions based on targeted
disruption of cytokine-induced pathology in parasitic infections, and
to initiate or accelerate development of such therapies for clinical
use.  The specific goals of these studies may include:

1.  identification and definition at the molecular level of the
immunopathogenic role played by individual cytokines in parasitic
diseases of humans or in animal models relevant to such diseases;

2.  production, characterization and/or improvement of specific
inhibitors (e.g., monoclonal antibodies, counterregulatory cytokines,
synthetic cytokine antagonists, or pharmacologic agents) of those
cytokines found to have pathogenic roles; and

3.  testing the efficacy and safety of such inhibitors in ameliorating
disease in relevant animal models or in limited phase I/II trials in
clinical settings.

It is likely that some potentially relevant inhibitors are already in
existence or under development for other purposes in either private
industry or public institutions.  As noted above, in such cases
collaborative research arrangements, including the use of consortia or
subcontracts, are encouraged.

SPECIAL REQUIREMENTS

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 should be included with the
application.

Principal Investigators should budget for an annual, three-day trip to
the Washington, DC, area for the Annual Meeting of the NIAID
International Centers for Tropical Diseases Research (ICTDR).  These
meetings will allow investigators to meet with other participants
capable of providing access to relevant patient populations.  In
keeping with the objectives of the ICTDR Program, it is expected that
such meetings will facilitate collaboration between basic and clinical
researchers and expedite clinical application of research findings
where appropriate.  Applicants should include a statement indicating
their willingness to participate in these meetings.

STUDY POPULATIONS

SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH
POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL
RESEARCH STUDY POPULATIONS

NIH policy is that applicants for NIH clinical research grants and
cooperative agreements are required to 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.  In addition, gender and
racial/ethnic issues must be addressed in developing a research design
and sample size appropriate for the scientific objectives of the study.
This information must be included in the form PHS 398 (rev. 9/91) in
Sections 1-4 of the Research Plan AND summarized in Section 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 is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

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,
every effort should be made 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 United States' 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 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 policies.

NOTE:  Peer review groups need adequate information about the
composition of proposed study populations in all applications involving
human subjects.  To avoid delays in review of such applications, the
NIAID advises that, as a minimum, the application should contain
demographic data about the clinic and/or in-patient population from
which study subjects will be drawn: average hospital admission per
year; percentage distribution of Black/Hispanic/other
minority/non-minority populations; gender; etc.  Studies using
non-hospital populations, such as community-based studies, should
provide similar data about populations in the area or region from which
the study subjects will be drawn.  In the absence of current data,
historical demographic information and/or previous recruitment data for
similar studies from the proposed study sites should be provided.

LETTER OF INTENT

Prospective applicants are asked to submit, by June 15, 1993, a letter
of intent that includes a descriptive title of the proposed research,
the names and affiliations of proposed key investigators, 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, 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 possible conflict of interest in
the review.  The letter of intent is to be sent to Dr. Olivia Preble at
the address listed under INQUIRIES.

APPLICATION PROCEDURES

Applications are to be submitted on form PHS 398 (rev. 9/91), the
standard application form for research grants.  Application kits are
available at most institutional offices of sponsored research and may
be obtained from the Office of Grants Inquiries, Division of Research
Grants, National Institutes of Health, Westwood Building, Room 449,
Bethesda, MD 20892, telephone 301/710-0267.  Applicants must adhere to
the format and requirements specified in the PHS 398 application kit.

For purposes of identification and processing, mark "yes" in item 2a on
the face page of the application and type in the RFA number AI-93-015
and the title "Immunologic Intervention in Parasitic Diseases."  The
RFA label available in the form PHS 398 must be affixed to the bottom
of the face page of the original application.  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 signed, typewritten original of the application, including the
Checklist, and three exact single-sided copies must be sent to:

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

At the time of submission, two additional copies must also be sent to:

Dr. Olivia Preble
Microbiology and Immunology Review Section
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C-20
6003 Executive Boulevard
Bethesda, MD  20892

To ensure their review, applications must be received by both the
Division of Research Grants and Dr. Olivia Preble by July 22, 1993.
Applications not received on the special date will be considered
non-responsive and will be returned to the applicant without review.
If the application submitted in response to this RFA is substantially
similar to a grant application already submitted to the NIH for review,
but has not yet been reviewed, the applicant will be asked to withdraw
either the pending application or the new one.  Simultaneous submission
of identical applications will not be allowed, nor will essentially
identical applications be reviewed by different review committees.
Therefore, an application cannot be submitted in response to this RFA
that is essentially identical to one that has already been reviewed.
This does not preclude the submission of substantial revisions of
applications already reviewed, but such applications must include an
introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Review Procedures

Applications will be reviewed by DRG staff for completeness and by
NIAID staff to determine administrative and programmatic responsiveness
to this RFA.  Those judged to be incomplete or nonresponsive will be
returned to the applicant without review.  Those considered complete
and responsive may be subjected to a triage review by an NIAID peer
review group to determine their scientific merit relative to the other
applications submitted in response to this RFA.  The NIH will withdraw
from competition those applications judged by the triage peer review
group to be noncompetitive for award and will so notify the applicant
investigator and the institutional business official.  Those
applications judged to be competitive for award will be 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.

Review Criteria

The factors to be considered in scientific review of the application
are:

1.  Scientific merit of research approach, design, and methodology as
well as the potential scientific, technical or medical significance of
the proposed research.

2.  Research experience and competence of the Principal Investigator(s)
and other staff to conduct the proposed studies.

3.  Adequacy of the time (effort) which the Principal Investigator(s)
and staff would devote to the proposed studies.

4.  Adequacy of facilities, including, if relevant to the proposed
research, adequacy of the clinical facilities and patient availability
for clinical studies.

AWARD CRITERIA

In selecting applications for funding, while scientific merit is of
primary consideration, applications will also be evaluated for
programmatic relevance and potential for impact on the clinical
management of parasitic diseases. Particular attention will be paid to
studies that target severe or multiple manifestations of disease that
contribute substantially to adverse outcomes.

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Dr. B. Fenton Hall
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Solar Building, Room 3A-36
Bethesda, MD  20892
Telephone:  (301) 496-7115
FAX: (301) 402-0804
E-mail:  bfh@exec.niaid.pc.niaid.nih.gov

Address the letter of intent and direct any questions regarding review
procedures to:

Dr. Olivia Preble
Microbiology and Immunology Review Section
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C-20
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-8208
FAX:  (301) 402-2638

Direct inquiries regarding fiscal matters to:

Mr. Todd Ball
Grants Management Branch
National Institute of Allergy and Infectious Diseases
Solar Building, Room 3A-37
Bethesda, MD  20892
Telephone:  (301) 496-7075
FAX:  (301) 480-3780

Schedule

Letter of Intent Receipt Date:  June 15, 1993
Application Receipt Date:       July 22, 1993
Scientific Review Date:         November 1993
Council Meeting Date:           February 1994
Earliest Award Date:            April 1, 1994

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.856, Microbiology and Infectious Disease 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 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.

.

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