VACCINE IMMUNOLOGY BASIC RESEARCH CENTERS

Release Date:  May 13, 1999

RFA:  AI-99-008

P.T.

National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  July 16, 1999
Application Receipt Date:  November 24, 1999

APPLICATIONS IN RESPONSE TO THIS REQUEST FOR APPLICATIONS (RFA) MUST BE PREPARED
USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS FOR
COMPLETING THE APPLICATION ARE IN AN NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR
APPLICATIONS FOR MULTI-PROJECT AWARDS."

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH), invites applications for program project grants that
address fundamental immune mechanisms as a basis for effective human vaccine
development.  Each program project should focus on a specific human infectious
disease of public health importance, excluding the human immunodeficiency virus
(HIV) and its sequelae.  Project teams should include expertise in basic
immunology, clinical research, and in the biology of the pathogenic organism. 
This program seeks to support interdisciplinary approaches to discover, define,
and analyze protective immune mechanisms in humans.  Utilization of insights and
approaches from recent advances in basic immunobiology in order to analyze immune
responses to vaccination and infection should facilitate the identification of
new targets and strategies for effective vaccines.

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 RFA, "BASIC VACCINE IMMUNOLOGY
RESEARCH CENTERS," is related to the priority areas of immunization and
infectious diseases.  Potential applicants may obtain a copy of "Healthy People
2000" at http://www.crisny.org/health/us/health7.html.

ELIGIBILITY REQUIREMENTS

Research grant applications may be submitted by domestic 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.  Foreign organizations are not
eligible to apply.  Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

The mechanism of support will be the program project (P01) grant.  This type of
award supports broadly based multidisciplinary research programs that have a
well-defined central research focus or objective.  An important feature is that
the interrelationships among the individual scientifically meritorious projects
will result in a greater contribution to the overall program goals than if each
project were pursued individually.  The program project grant consists of a
minimum of three interrelated individual research projects that contribute to the
program objective.  The award also can provide support for certain common
resources termed cores.  Such resources should be utilized by two or more
projects within the award.

Responsibility for the planning, direction, and execution of the proposed
projects will be solely that of the applicant.  At this time, the NIAID is
administratively limiting the duration of P01 grants to four years; this
administrative limitation may change in the future.  The earliest anticipated
award date is July 1, 2000.

FUNDS AVAILABLE

The estimated total funds (direct and facilities & administrative (F&A))
available for the first year of support for this RFA will be $3.0 million.  In
fiscal year 2000, the NIAID plans to make approximately 4 awards related to this
RFA.  This level of support is dependent on the receipt of a sufficient number
of applications of high scientific merit.  Applications requesting budgets in
excess of $750,000 in total (direct and F&A) costs in the first year must obtain
approval from the Program contact listed in INQUIRIES prior to submission.  The
usual PHS policies governing grants administration and management will apply. 
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.  At this time, the NIAID has not determined whether or how this
solicitation will be continued beyond the present RFA.

RESEARCH OBJECTIVES

Background

New vaccination approaches are needed to control major infectious diseases that
are spreading with devastating consequences worldwide.  Development of effective
vaccines for complex, often chronic diseases such as tuberculosis, malaria, and
hepatitis C, as well as for other viral, bacterial, fungal, and parasitic
diseases, would be greatly facilitated by comprehensive information on protective
immune mechanisms in humans.  Better understanding of the immunological basis of
vaccines should also enable the rational improvement of existing vaccines and
guide the development of new vaccines against emerging infections and agents of
bioterrorism.  Our current understanding of protective immunity is incomplete in
many areas, including for example, the cellular events triggered by microbial
invasion, immune effector cell activation and routing to sites of infection,
development of immunological memory, and the corresponding immune-evasive
strategies of the pathogen.  Further, these processes need to be understood in
the context of the immunobiology of the tissues and organs that are disease
targets.  Thorough analysis of disease specific human immune responses should
contribute to vaccine improvement by identifying important targets for
immunization strategies.  Many different cell types function in immune responses
to microbial pathogens, including neutrophils and other granulocytes, distinctive
subsets of antigen presenting cells, natural killer cells, gamma-delta T cells,
CD1-restricted T cells, and diverse B- and T-cell populations.  Understanding
their integrated role in immunity to specific infections would enable rational
approaches to engage the most critical components by vaccination.

Recent advances in basic immunology, the genetics and biology of human pathogens,
and human clinical research present new opportunities to analyze pathogen-host
defense interactions on a mechanistic level.  Basic immune mechanisms are being
defined in such areas as antigen processing and presentation, T and B cell
differentiation and memory, the molecular basis of antigen recognition, and the
innate immune system.  The development and application of new methods, such as
soluble peptide-MHC conjugates, have advanced the analytical capabilities of
basic immunology research in disease settings.  Pathogenesis research is also
advancing rapidly.  An abundance of vaccine-relevant information is emerging from
research on microbial genomes and functions of microbial gene products in
infection. Support will be provided for research programs that make use of new
information and methodologies to discover, define, and analyze human protective
immune responses to infection and vaccination.

Research Objectives and Scope

The overall goal of establishing this new research program is to stimulate in-
depth investigations of fundamental immunological mechanisms relevant to
vaccines.  Proposed studies will require focusing on a specific human disease in
need of a vaccine, excluding HIV/AIDS.  This may include infectious agents of
bioterrorism.  The disease selected should reflect the expertise of the proposed
collaborators as well as the availability of human clinical materials and the
availability of tools for immunological analyses.  Studies are intended to focus
on human immune responses and to make use of human clinical materials wherever
possible.  Projects that incorporate clinically relevant animal models into a
complementary framework of human studies may be proposed, if adequate
justification regarding their significance for human vaccine design is provided. 
Assembling a group of collaborators with expertise in basic immunology, clinical
research, and the biology of the infectious agent is essential.  Applications may
be submitted by single institutions or consortia of institutions as may be
appropriate to provide the requisite types of expertise.  Applications must also
demonstrate that effective research collaborations can be carried out.

The central focus of the proposed research should be the analysis of fundamental
immune interactions that lead to protective immunity.  Important issues for many
diseases include understanding the events by which specific infections trigger
immune responses, mechanisms of immune cell localization in target organs,
definition of the critical immune effector functions that effectively combat the
infection, and the development and persistence of immunological memory.  Research
topics of interest include, but are not limited to, the following:

o  immune system-pathogen interactions that shape immune responses and influence
the development of immunological memory;
o  approaches to immunogen and adjuvant design and strategies based on
understanding the disease process and triggering the needed type of immune
response;
o  novel methods of in vivo analyses of immune effector cells and molecules;
o  analysis of mucosal immune responses to inhaled or ingested infectious agents
related to bioterrorist strategies; and
o  mechanisms of immune evasion by the microbial agent and the exploration of
strategies to circumvent evasion.

Clinical testing of vaccine candidates is not within the scope of this RFA.

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 in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear, compelling rationale,
and justification are provided that inclusion is inappropriate with respect to
the health of the subjects or 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", 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 which is available via the WWW. at:
https://grants.nih.gov/grants/guide/notice-files/not94-100.html

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by the
NIH, unless there are scientific and ethical reasons not to include them.  This
policy applies to all initial (Type 1) applications submitted for receipt dates
after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for Grants
and Contracts, March 6, 1998, and which is available at the following URL
address:  https://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators may obtain copies from these sources or from Dr. Charles Hackett
(listed in INQUIRIES below) who may also provide additional relevant information
concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by July 16, 1999, 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.  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.
Priti Mehrotra at the address listed under INQUIRIES.

APPLICATION PROCEDURES

Applicants for P01 grants must follow special application guidelines in the NIAID
Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS (April
1999); this brochure is available from NIAID staff listed in INQUIRIES below and
via the WWW at: http://www.niaid.nih.gov/ncn/grants/multibron.htm

Applications are to be submitted on the standard research grant application form
PHS 398 (rev. 4/98).  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:
GrantsInfo@nih.gov.  Applications are also available on the World Wide Web at 
https://grants.nih.gov/grants/forms.htm.

For purposes of identification and processing, item 2 on the face page of the
application must be marked "YES" and the RFA number "AI-99-008" and the words
"BASIC VACCINE IMMUNOLOGY RESEARCH CENTERS" must be typed in.

The RFA label and line 2 of the application should both indicate the RFA number. 
The RFA label 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.

The sample RFA label available at:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to allow
for this change.  Please note this is in pdf format.

Applications must be received by November 24, 1999.  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. 4/98) Application Kit (as modified in,
and superseded by, the NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR
MULTI-PROJECT AWARDS" [April 1999]), will be judged non-responsive and will be
returned to the applicant.

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.

It is highly recommended that the appropriate NIAID program contact be consulted
before submitting the letter of intent and during the early stages of preparation
of the application.  (See program contact under INQUIRIES).

Submit a signed, typewritten original of the application, including the
checklist, and three signed, exact, single-sided photocopies, in one package 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, two additional exact copies of the grant application
and all five sets of any appendix material must be sent to Dr. Priti Mehrotra at
the address listed under INQUIRIES.

Concurrent submission of an R01 and a Component Project of a Multi-project
Application: Current NIH policy permits a component research project of a multi-
project grant application to be concurrently submitted as a traditional
individual research project (R01) application.  If, following review, both the
multi-project application and the R01 application are found to be in the fundable
range, the investigator must relinquish the R01 and will not have the option to
withdraw from the multi-project grant.  This is an NIH policy intended to
preserve the scientific integrity of a multi-project grant, which may be
seriously compromised if a strong component project(s) is removed from the
program.  Investigators wishing to participate in a multi-project grant must be
aware of this policy before making a commitment to the Principal Investigator and
awarding institution.

SPECIAL INSTRUCTIONS FOR COMPLETION OF APPLICATIONS IN RESPONSE TO THIS RFA

Applicants for P01 grants must follow special application guidelines in the NIAID
Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS (April
1999); this brochure is available from NIAID staff listed in INQUIRIES below and
via the WWW at: http://www.niaid.nih.gov/ncn/grants/multibron.htm

The brochure presents specific instructions for sections of the PHS 398 (rev.
4/98) application form that should be completed differently than usual.  For all
other items in the application, follow the usual instructions on pages 5-20 of
the PHS 398 booklet.

REVIEW CONSIDERATIONS

Review Procedures

Upon receipt, applications will be reviewed for completeness by the NIH Center
for Scientific Review and for responsiveness by NIAID staff.  Incomplete and/or
non-responsive applications will be returned to the applicant without further
consideration.  Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer review group
convened by the NIAID in accordance with the review criteria stated below.  As
part of the initial merit review, a streamlining process may be used in which all
applications will receive a written critique and undergo a process in which only
those applications deemed to have the highest scientific merit will be discussed,
assigned a priority score, and receive a second level of review will by the
National Advisory Allergy and Infectious Diseases Council.

Review Criteria

The general criteria for P01 grant applications are presented in the NIAID
brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS (April
1999); this brochure is available from NIAID staff listed in INQUIRIES below and
via the WWW at: http://www.niaid.nih.gov/ncn/grants/multibron.htm

In addition to the general criteria, the following specific criteria will also
be used in the evaluation of applications:

SIGNIFICANCE-Quality of the proposed research in the analysis of fundamental
immune interactions that lead to protective immunity.

APPROACH-Adequacy of the plans to use new information and methodology to
discover, define, and analyze human protective immune responses.

INVESTIGATORS-Adequacy of the expertise of the proposed investigators in basic
immunology, clinical research and the biology of the infectious disease agent. 
Applications must also demonstrate that effective research collaborations can be
carried out.

AWARD CRITERIA

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

Requests for the NIAID brochure "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS" as well as inquiries regarding programmatic (eligibility and research
scope) issues, may be directed to:

Charles J. Hackett, Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Room 5145, MSC 7640
Bethesda, MD 20892-7640
Telephone:  (301) 496-7551
FAX:  (301) (402-2571
Email:  ch187q@nih.gov

Direct inquiries regarding preparation of the application and review issues, and
address the letter of intent to, and mail two copies of the application and all
five sets of appendices to:

Dr. Priti Mehrotra
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Room 2100, MSC 7610
Bethesda, MD  20892-7610
Telephone:  (301) 435-9369
FAX:  (301) 402-2638
Email: pm158b@nih.gov

Direct inquiries regarding fiscal matters to:

Pamela G. Fleming
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Room 2119, MSC 7610
Bethesda, MD 20892-7610
Telephone:  (301) 402-6580
FAX:  (301) 480-3780
Email:  pf49e@nih.gov

Schedule

Letter of Intent Receipt Date:  July 16, 1999
Application Receipt Date:       November 24, 1999
Scientific Review Date:         April 1, 2000
Advisory Council Date:          June, 2000
Earliest Date of Award:         July 1, 2000

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. 93.855 - Immunology, Allergy, and Transplantation
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 Public Health Service 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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