Full Text AI-94-003

NEONATAL IMMUNITY FOR VACCINES

NIH GUIDE, Volume 22, Number 42, November 19, 1993

RFA:  AI-94-003

P.T. 34

Keywords: 
  Immune System 
  Vaccine 
  Infants 


National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  January 15, 1994
Application Receipt Date:  March 10, 1994

PURPOSE

The Division of Allergy, Immunology and Transplantation (DAIT) and
the Division of Microbiology and Infectious Diseases (DMID) of the
National Institute of Allergy and Infectious Diseases (NIAID) invite
applications for basic and preclinical studies to increase knowledge
of the development and function of the immune system in the neonate.
Applications are especially solicited that address the utilization of
this information for the development of new anti-pathogen vaccines
effective in this age group.  The knowledge developed through this
initiative would also be applicable to the development of vaccines
for autoimmune and allergic 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), Neonatal Immunity for Vaccines, is related to
the priority areas of diabetes and chronic disabling diseases, and
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).

ELIGIBILITY REQUIREMENTS

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 or
local governments, and eligible agencies of the Federal government.
Foreign institutions are not eligible to apply for First Independent
Research Support and Transition (FIRST) (R29) Awards.  Applications
from minority individuals and women are encouraged.

MECHANISM OF SUPPORT

The mechanisms of support will be the individual research project
grant (R01) and the FIRST (R29) award.  Multidisciplinary approaches
that involve collaborative efforts among investigators in the fields
of basic immunology, molecular biology, cell biology, biochemistry,
and infectious disease are strongly encouraged.  The total project
period for applications submitted in response to this RFA may not
exceed five years; foreign applications may not request more than
three years of support.

This RFA is a one-time solicitation.  Future competing renewal
applications will compete with all investigator-initiated
applications and will be reviewed according to customary referral and
review procedures.

FUNDS AVAILABLE

The estimated funds available for the total (direct and indirect)
first year costs of all awards made under this RFA will be
$1,500,000.  In Fiscal Year 1994, the NIAID plans to fund
approximately seven R01s/R29s.  Applications should not request more
than four percent annual inflationary increases for future years.
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.

RESEARCH OBJECTIVES

Background

Infant mortality worldwide and in our inner cities is a continuing
problem.  Infants are at risk for overwhelming bacterial and viral
infections.  In order to meet the Childhood Vaccine Initiative goal
of immunizing infants as early in life as possible, greater
understanding of the neonatal immune system is necessary.  A Blue
Ribbon Panel convened by the NIAID in March of 1993 was charged with
developing priorities for research in the area of vaccines.  One of
the areas highlighted by the panel was the need for basic research in
immunology as it relates to vaccine research.  In particular, the
panel emphasized the need for basic research in the area of neonatal
immunity.

The immune system of the infant is functionally immature.  Neonates
do not produce much immunoglobulin.  Maternal antibodies are
transferred late in gestation to the fetus.  This maternal antibody
offers short term protection for the neonate.  The role of this
maternal antibody in the decreased response of the neonate's own
immune system is unclear.

The neonate's immune response to challenge from infectious agents is
also deficient.  Enhanced understanding of the neonatal response to
pathogens and the potential for interference by maternal antibody in
the function of the neonatal immune system is needed.

Research Objectives and Scope

The goal of this RFA is to increase knowledge of the development and
function of the neonatal immune system and to use this knowledge to
develop new and more effective vaccine strategies for this age group.
Studies involving human tissues and cells are especially encouraged.
Examples of relevant research topics are given below.  These
examples, however, are not intended to be all inclusive or limiting:

o  role of natural or vaccine-induced maternal antibodies, or in
utero antigen exposure, in the development of and regulation of the
immune response of the neonate

o  mechanisms of immunosuppression/immunopotentiation in neonates
exposed to pathogens or pathogen-derived antigens, and the long-term
consequence of this neonatal exposure for development of the
immunologic repertoire

o  ontogeny of the immune response in neonates and infants

o  characterization of antigens that elicit protective immune
responses against pathogens in neonates, and methods to enhance such
responses

In preparing an application in response to this RFA, the applicant
should bear in mind the research objectives of this RFA.
Applications must be prepared according to the instructions in form
PHS 398 (rev. 9/91).

STUDY POPULATIONS

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

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
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,
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
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 therefore requires that, as a minimum, the
application must contain demographic data about the clinic and/or
in-patient population from which study subjects will be drawn:
average hospital admissions 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 sites should
be provided.

LETTER OF INTENT

Prospective applicants are asked to submit, by January 15, 1994, a
letter of intent that includes a descriptive title of the overall
proposed research, the name, address and telephone number of the
Principal Investigator (Program Director), and the number and title
of this RFA.  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 INQUIRIES.

APPLICATION PROCEDURES

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
"NEONATAL IMMUNITY FOR VACCINES" must be typed in.

These application forms may be obtained from the institution's office
for sponsored research or its equivalent and from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone (301) 435-0714.

It is highly recommended that the Chief of the Autoimmunity Section,
Clinical Immunology Branch be contacted in the early stages of
preparation of the application.  (See program contact in INQUIRIES
below.)

Applications must be received by March 10, 1994.  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. 9/91)
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.
First (R29) applications must include at least three sealed letters
of reference attached to the face page of the original application.
First (R29) applications submitted without the required number of
reference letters will be considered incomplete and will be returned
without review.

Applications received after the receipt date will be returned 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.

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

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
provided below in 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.

REVIEW CONSIDERATIONS

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 will 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 by the reviewers 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.  Applicants may receive an abbreviated summary statement
together with essentially unedited reviewers' comments.  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.

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 a given
application may influence the recommendation of the Advisory Council
concerning funding of that application.

AWARD CRITERIA

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

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:

Elaine Collier, M.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4A20
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7985
FAX:  (301) 402-2571

Direct inquiries regarding review issues; 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 4C19
6003 Executive Boulevard
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
6003 Executive Boulevard
Bethesda, MD  20892***
Telephone:  (301) 496-7075

Schedule

Letter of Intent Receipt Date:  January 15, 1994
Application Receipt Date:       March 10, 1994
Scientific Review Date:         July 1994
Advisory Council Date:          September 1994
Earliest Award Date:            September 1994

AUTHORITY AND REGULATIONS

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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