Full Text AI-93-08

COLLABORATIVE MUCOSAL IMMUNOLOGY GROUPS FOR AIDS VACCINES

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

RFA:  AI-93-08

P.T. 34

Keywords: 
  AIDS 
  Immunology 
  Vaccine 
  Bioassay 
  Disease Model 


The National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  April 15, 1993
Application Receipt Date:  May 21, 1993

PURPOSE

The Vaccine Research and Development Branch (VRDB) of the Division of
Acquired Immunodeficiency Syndrome (DAIDS) within the National
Institute of Allergy and Infectious Diseases (NIAID) announces
availability of an RFA for funding of new Collaborative Mucosal
Immunology Groups (CMIGs) for AIDS vaccines.  The purpose of this RFA
is to invite research grant applications for collaborative projects
from investigators pursuing research on mucosal immunity to Human
Immunodeficiency Virus and/or Simian Immunodeficiency Virus (SIV) to
participate in a network of CMIGs for AIDS vaccines.  The urgent need
to control the spread of AIDS has fueled efforts to develop safe and
effective AIDS vaccines.  Additional basic and preclinical research
is needed in the area of vaccine induction of mucosal immunity to
AIDS viruses (HIV and SIV).  The NIAID wishes to encourage and expand
research in the area of mucosal immunology to AIDS viruses, that will
focus on:  (1) design and development of novel recombinant vectors
and/or AIDS vaccine formulations designed to induce regional mucosal
immunity particularly in the female or male reproductive tracts and
in the rectum (gut); (2) characterization of the components (T cells
and antibodies) and their mechanism of action in the immune responses
at mucosal surfaces, that are specific for HIV/SIV antigens; and (3)
development of immunization strategies to prevent mucosal HIV
infection and transmission.

The special feature of this program is the concurrent submission of
research grant applications by investigators who wish to collaborate
on a common theme related to mucosal immunity to AIDS viruses, but do
not require extensive shared physical resources or core functions to
conduct their research.  In order to be responsive to this RFA, a
minimum of two independent investigators with related research
objectives should submit concurrent, collaborative,  individual
research grant applications that address a common theme.  The common
theme for any group should include a multidisciplinary approach,
specifically in the areas of immunology and virology, since this
likely to be essential to develop vaccines that will induce mucosal
immunity and block sexual transmission of HIV.  Investigators now
participating in the National Cooperative Vaccine Development Group
(NCVDG) that have pursued this area of research and new applicant
groups are invited to apply.  Applications from the private sector
(e.g., vaccine, pharmaceutical, or biotechnological companies) are
encouraged.  Collaborative arrangements involving more than one
institution are especially encouraged.

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), Collaborative Mucosal Immunology Group for
AIDS Vaccines, is related to the priority area of HIV infection.
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.
Applications from minority individuals and women are encouraged.

MECHANISM OF SUPPORT

The support mechanism for this program will be the individual
research grant (R01).  Thus, it is the responsibility of the
applicants to plan, direct and execute the proposed projects in
accord with their interests and perceptions of approaches to the
study of mucosal immunity in AIDS vaccine development.

In order to be responsive to this RFA, a minimum of two independent
investigators, representing diverse scientific disciplines with
related research objectives should submit concurrent, collaborative,
cross-referenced individual R01 applications that address a common
theme.  Each application must include a succinct description of the
scientific relationship among the group of R01s and plans for
collaboration, interaction, and communication among investigators in
the group of applications.  Collaborative arrangements involving more
than one institution are especially encouraged.

The Principal Investigator of one R01 within a collaborative group
should be identified as the Collaborative Project Coordinator to be
responsible for the coordination of collaborative efforts; that
investigator may request funds, not to exceed 10 percent of direct
costs, for an administrative core to include the time and effort
contributed toward coordination of overall research.  Scientific
cores also are permitted to support core facilities which will
benefit the Group as a whole.  PIs proposing such cores may request
funds up to 20 percent of direct costs of the total CMIG to support
scientific core efforts and activities.

In addition, for all investigators participating in a Collaborative
Group, at least 30 percent of direct costs should be specified for
shared resources and collaborative studies that are necessary for the
shared research goals.  Applicants are requested to furnish their own
estimates of the time required to achieve the objectives of the
proposed research project.  Up to four years of support may be
requested.

Because the nature and scope of the research proposed in response to
this RFA may vary, it is anticipated that the size of the awards will
vary also.  The budget request for the initial year's total costs
(direct and indirect) for any group may not exceed $500,000 and the
total requested cost of each R01 application within a group must not
exceed $180,000.  Any budgets in excess of this amount must be
approved by NIAID Program in advance of submission of the Group
application.  Requests for expensive pieces of equipment are not
encouraged and any requests for equipment must be especially
well-justified.  In addition, groups using non-human primates should
not budget for more than a limited number of animals under this
mechanism.  Access to additional animals may be provided through
other NIAID-funded resources, such as the SIV Vaccine Evaluation Unit
contracts and an Interagency Agreement with NCI for a chimpanzee unit
for investigations on AIDS vaccines.

This RFA is a one-time solicitation.  If by the end of the third
year, the NIAID has not announced its intent to readvertise this RFA,
incumbents may prepare unsolicited competing continuation R01
applications that will compete with all investigator-initiated
applications and be reviewed according to the customary peer review
procedures.  Those PIs who wish to continue collaborative efforts
should consult NIAID staff before preparing an application.

All current policies and requirements that govern the research grant
programs of the NIH will apply to grants awarded in connection with
this RFA.

FUNDS AVAILABLE

The NIAID anticipates making three to five awards to Groups (6 to 15
R01 awards), based on highest program priorities, as a result of this
RFA.  The NIAID has set aside $1.4 million (total costs) for the
initial year of funding applications received in response to the RFA.
The final number and specific amounts of awards to be made  will
depend upon the scientific and technical merit, as reflected in the
priority scores, relevance to programmatic priorities, and the
availability of funds.

RESEARCH OBJECTIVES

Background

As HIV continues its relentless spread into a wider population base,
it is becoming apparent that the U.S. is now facing a second wave of
infections.  As has already been seen in Africa, this second wave is
striking down almost equal numbers of young women and men in the
young adult segment of the population.  In our inner cities, it is
already evident that young women in their early child-bearing years
are becoming HIV-infected at alarming rates.  Like several other
sexually-transmitted diseases, HIV is transmitted from mother to
infant.  Because the primary mode of transmission is exposure to
virus (or potentially to virus-infected cells) delivered to mucosal
surfaces during sexual intercourse, it is essential that efforts to
develop successful AIDS vaccines must be directed to strategies that
will protect individuals against transmission across the mucosal
surfaces of the female and male reproductive tracts and mucosal
surfaces.

Although great strides have been made in our understanding of HIV and
of the immunologic responses to HIV antigens, the development of a
safe and effective vaccine against HIV remains a formidable
challenge.  Research initiatives to develop both novel vaccine
strategies and effective adjuvants have been launched to help achieve
this goal.  The VRDB, in the DAIDS, within the NIAID has undertaken a
leading role in AIDS vaccine research and has organized the National
Cooperative Vaccine Development Group (NCVDG), whose purpose is to
spearhead investigator-initiated basic research in AIDS vaccine
development.  In the preclinical research area, the VRDB has also
supported other preclinical studies that complement NCVDG studies,
including the AIDS Cooperative Adjuvant Group, several SIV Vaccine
Evaluation Unit contracts and an Interagency Agreement with NCI for a
chimpanzee unit for investigations on AIDS vaccines.  Clinical trials
of AIDS vaccines in the AIDS Vaccine Evaluation Group funded by the
NIAID, have tested a series of HIV-1 envelope vaccine candidates with
different compositions, formulations and delivery systems.  These
trials continue to expand with plans to evaluate new candidate
vaccines in additional groups of volunteers.

To date, extensive efforts using animal models have been directed
almost exclusively toward understanding the mechanism of protection
against intravenous (IV) viral challenge induced by parenteral
administration of AIDS vaccines.  In addition, specific efforts have
been directed toward evaluating the serological and cellular immune
responses to HIV induced by vaccination of human volunteers in Phase
I/II clinical trials.  However, studies of mucosal immunity to
HIV/SIV in humans and animals lag far behind those of systemic
immunity to HIV, particularly in vaccine studies.  Although the
primary route of exposure for HIV in this worldwide epidemic is
through mucosal surfaces, vaccines currently available have not been
specifically targeted to induce immune responses that would
effectively block mucosal transmission.  Induction of virus-specific
mucosal immunity capable of preventing or minimizing infectious
events may provide the greatest opportunity to avert HIV disease in
an individual and block HIV transmission to sexual partners or to
infants. Thus, potent, efficacious AIDS vaccines must be designed to
elicit comprehensive and long-lasting immune responses to HIV, both
systemically and at mucosal surfaces.

Objectives and Goals

The fundamental objective of the VRDB in the DAIDS is to develop safe
and effective vaccines for the prevention of transmission of HIV-1,
the causative agent of AIDS.  Because HIV infection occurs primarily
as a result of exposure during sexual intercourse, the development of
vaccine strategies to protect individuals from infection at mucosal
surfaces is imperative.

The goals of the network of the Collaborative Mucosal Immunology
Groups for AIDS Vaccines (CMIGs) are several. First, the groups aim
to conceptualize, design, and develop (evaluate immunogenicity) of
AIDS vaccines that might protect against HIV transmission across
mucosal surfaces.  In addition, the effort will require the
development of assays and technology to evaluate humoral and cellular
mucosal immunity induced by candidate AIDS vaccines in primates and
humans.  Data from these studies will contribute to our understanding
of what component(s) of the immune response correlate with protection
against sexual transmission of HIV.

Research Scope

Applications are invited that seek to discover/design and develop
vaccine strategies, animal models, methodologies, and assay reagents
to study mucosal immunity to HIV (and SIV) in primates and/or humans.
Applications for this RFA should stress creative approaches to the
discovery, development and evaluation of candidate AIDS vaccines that
might be effective.  The following two general research areas are
specifically encouraged under this RFA

o  Development and use of animal models to explore novel strategies
(vectors or formulations) for vaccination and protection against
mucosal challenge with AIDS viruses.

o  Development of assays, reagents and technology to evaluate
specific, protective mucosal immune responses induced by AIDS
vaccines in animals and human volunteers.

Of particular interest is the integration of immunology and virology
projects leading
to productive interdisciplinary approaches that elucidate the basis
of protective mucosal immunity to sexually-transmitted HIV
infections.

The objectives and goals of the application should be relevant and
compatible with the missions and directions of the DAIDS and the
NIAID, as stated in this RFA.

While it is anticipated that complete development of new mucosal AIDS
vaccines will not occur within the project period for all Groups, a
rationale for the most likely utility of discoveries made or an
outline of a plan for eventual clinical trials should be included.

Specific Objectives

Examples of research areas of mucosal immunity for AIDS vaccines of
high priority and that would be responsive to RFA may include, but
are not limited to those listed below.  These research topics are
intended to provide a perspective on the scope of research that would
meet the objective of this program.  It is not required that all or
any of them be included in a particular group of applications.

o  Development and analysis novel AIDS vaccine strategies, vectors,
delivery systems, or adjuvant formulations that would stimulate
protective mucosal immunity, particularly in the genital tract in
primate models.  These strategies might include studies to provide
improved antigen presentation that would induce long-lasting cellular
immunity, or effective priming of T-cell responses to AIDS viruses
potentially in humans.

o  Development of methods to evaluate mucosal immunity to
lentiviruses in humans and primates.  For example, development of
assays for detection of HIV-specific immune cells or IgA and IgG in
dilute or complex fluids (vaginal washings or seminal plasma) and
specimens from mucosal sites (e.g., biopsy tissue from cervical
mucosa or rectal/intestinal mucosa, swabs or scrapings from cervix
and other tissue smears).

o  Identification and evaluation of functional antibody responses
that might be effective in preventing HIV or SIV mucosal
transmission.  Analysis of the mechanism of action of antiviral
polyclonal or monoclonal IgA antibodies by evaluation of their
ability to neutralize or inactivate HIV or facilitate killing of
virus-infected cells.

o  Identification and characterization of mucosal cell-mediated
immune responses (regional cytotoxic T lymphocytes (CTL) and helper T
cells); e.g., specific T-cell immune responses against HIV, that
might be a front-line defense in the reproductive tract or the gut.
Studies of vaccines that facilitate antigen presentation and increase
T-cell help; e.g., by inducing cytokines, at mucosal surfaces.

Restrictions and Exclusions

No clinical trials will be supported under this RFA. However,
proposed analysis of samples acquired from vaccinees in
NIAID-sponsored AIDS Vaccine Clinical Trials is appropriate and
should be discussed in detail with NIAID Program Staff.  Access of
existing samples from ongoing trials can be obtained for specific
experiments by individual request.  If samples, other than serum or
peripheral blood cells, that are needed for specific research be dies
could be obtained in future or already planned trials, early
discussion with NIAID Program Staff is essential to ensure their
availability.  Research efforts in animal model systems should be
focused on the basic research and preclinical immunological
evaluation of new vaccines or vaccine strategies to protect against
mucosal challenge.  If an application includes plans for extensive
use of primates, this should be discussed with Program Staff before
submission of the application.  Budgetary limitations will prohibit
extensive use of primates in these projects (See MECHANISM OF
SUPPORT).

Definitions

COLLABORATIVE PROJECTS.  An assistance mechanism for research
collaboration among at least two independent investigators utilizing
traditional research grants (R01s).  The special feature of this
program is the concurrent submission of research grant applications
by investigators who wish to collaborate on a common theme related to
mucosal immunity to AIDS viruses, but do not require extensive shared
physical resources or core functions to conduct their research.

COLLABORATIVE MUCOSAL IMMUNOLOGY GROUP FOR AIDS VACCINES (CMIGs).  In
this RFA the terms COLLABORATIVE MUCOSAL IMMUNOLOGY GROUP FOR AIDS
VACCINES and "Group" are synonymous.  A Group is composed of a
minimum of two independent investigators with related research
projects representing diverse scientific disciplines, but with
objectives that address a common theme:  the conceptualization,
development and application of new technology for the evaluation of
new vaccines and strategies for protective mucosal immunity to AIDS
viruses.  (See MECHANISM OF SUPPORT)

NETWORK OF COLLABORATIVE MUCOSAL IMMUNOLOGY GROUP FOR AIDS VACCINES -
(CMIG Network):  Awardees from this RFA, which include all of the
PIs, and NIAID staff will comprise the Network of Collaborative
Mucosal Immunology Groups for AIDS Vaccines (CMIG Network).

PRINCIPAL INVESTIGATOR (PI) - The investigator who submits each R01
and is responsible for the conduct of the research.  Limited funds
may be requested for scientific cores by one or more PIs.  Each PI is
also responsible for collaborative efforts within the group (See
SPECIAL CHARACTERISTICS and the additional instructions available
from the program staff listed under INQUIRIES for preparation of a
collaborative project application).

COLLABORATIVE PROJECT COORDINATOR (CPC) - The PI who is responsible
for organizing and maintaining effective collaboration and for
submitting the application package containing all the collaborative
projects.  This PI may request funds for an administrative core to
support these coordination efforts (See Section VIII "SPECIAL
CHARACTERISTICS" and the additional instructions provided with the
RFA for preparation of a collaborative project application).

NIAID COLLABORATIVE PROGRAM OFFICER (NIAID CPO) - A Senior or
Associate Scientist of the NIAID extramural staff and the immediate
contact person for the PIs in the individual Groups.  The
Collaborative Program Officer is responsible for the program
administration of the CMIGs and will be available to facilitate the
communication among the Groups and between NIAID and the individual
Groups and to serve as a source of information on resources.  The
responsibilities of the NIAID CPO are outlined under Special
Characteristics.

INVENTION - A new vaccine or diagnostic technique that is or may be
patentable under Title 35 of the United States Code.

o  Working Relationships Within Collaborative Projects

The special feature of this program is the concurrent award of
research grant support to investigators to collaborate on a common
theme related to mucosal immunity to AIDS viruses. We anticipate that
at least 30 percent of funds within each grant will be designated for
collaborative studies.  In addition, one Principal Investigator must
be identified as the Collaborative Project Coordinator, responsible
for coordination of the collaborative efforts of the Group.  The
efforts of the CMIGs will be facilitated by the NIAID Collaborative
Program Officer as outlined below (Special Characteristics - NIAID
Staff Involvement").

o  Intragroup Communications and Meetings

(Each applicant should include travel funds for these meetings when
they prepare their budgets.)  Applicants should include a statement
in their applications indicating their willingness to participate in
such meetings.

A critical determinant of Group success will be the degree of
effective communication among its members.  Therefore, it is
suggested that the group also hold regular conference calls if long
distances are a concern.  Regular telephone and written communication
among Group members will be important and is encouraged.  These
expenses should be included in the budget for the Administrative Core
and, where appropriate, within the budget for each project.

In addition, written updates on progress from the individual projects
(no more than 5 pages) should be submitted to the NIAID Collaborative
Program Officer in conjunction with the Group meetings.

Each Group should plan for two meetings of the Principal
Investigators each year (or more often if warranted) to review
progress, plan and design research activities, and establish
priorities; the NIAID Collaborative Program Officer may also attend
these meetings.  The Collaborative Project Coordinator will be
responsible for scheduling the time and place (generally at one of
the performance sites) and for notifying the NIAID Collaborative
Program Officer at least thirty days prior to the meeting date.

Funds for attending the two intra-Group meetings should be included
in each PIs budget.  The application for the Administrative Core
(from the Collaborative Project Coordinator) should also include
plans for scheduling the intra-Group meetings, notifying Group
members and the NIAID Collaborative Program Officer, and documenting
and disseminating Group meeting proceedings.  This investigator may
request funds, not to exceed 10 percent of direct costs, for the time
and effort contributed toward coordination of overall research.

o  CMIG Network Meetings

(Each applicant should include travel funds for these meetings when
they prepare their budgets.)  Applicants should include a statement
in their applications indicating their willingness to participate in
such meetings.

o  Annual meeting of the CMIG Network:  In addition to the two Group
meetings, one meeting each year will be held at a site designated by
the NIAID during which the Principal Investigators from each Group
will be invited to present significant findings in a symposium
format.  Whenever possible, this Network meeting will coincide with
meetings of investigators from the National Cooperative Vaccine
Development Groups (NCVDGs), the Primate Vaccine Evaluation Units,
the AIDS Cooperative Adjuvant Group, and/or the AIDS Vaccine Clinical
Trials Network.  This collaboration and coordination is critically
important to the success of the AIDS vaccine program and will be
facilitated by the NIAID Collaborative Program Officer.

o  Annual NCVDG meeting:  In addition, at least one representative
from each CMIG will be invited to attend the annual National
Cooperative Vaccine Development Group Meeting (NCVDG) meeting.

o  NIAID Staff Participation

The NIAID Collaborative Program Officer will be a member of the
professional (Senior Scientist or Section Chief) within the Vaccine
Research and Development Branch of the Division of AIDS, which is an
extramural program of the NIAID.  The Collaborative Program Officer
is assigned by the Vaccine Research and Development Branch Chief
based on his/her scientific expertise, interests and compatibility
with the Group's areas of research.  Because of the limited number of
awards anticipated under this RFA, there will be one individual
assigned to all of the CMIGs initially.  The Collaborative Program
Officer will also oversee the entire mucosal immunology program
(including the CMIG Network).  Through the NIAID Collaborative
Program Officer, the NIAID will exercise the usual stewardship
responsibilities inherent in the role of an NIH Health Science
Administrator.

The Collaborative Program Officer will serve as a resource for
information, access to laboratory testing, and biological reagents,
when such resources are not a usual requirement of the Group's
day-to-day research activities, but may be required on an occasional
basis.  A brief description of the resources available through the
Division of AIDS and the Vaccine Research and Development Branch is
enclosed with this RFA.  These resources are intended for qualified
studies and may not be available on a continual basis.  It is the
policy that, for any materials/samples that are received through the
Collaborative Program Officer, written approval must be obtained
before redistribution of any material/samples or dissemination of
data gathered from these materials/samples.  The following is a
partial list of some resources available from the NIAID that might be
of particular use to investigators:

o  Information and some resources for SIV and/or HIV antigens
(proteins) that may be used as immunogens in these studies for
investigators who may not have adequate access to SIV or HIV
antigens, subunits or peptide immunogens.

o  Expanded access to evaluate immunogenicity in primates for those
approaches that merit further study through contracts monitored by
the Vaccine Research & Development Branch.

o  Access to HIV or SIV vaccinee samples for evaluation where
investigators have demonstrated appropriate development of technology
and methods for characterization of mucosal immunity.

The principal end product of the research sponsored by the RFA will
be the development and analysis of promising AIDS vaccines and
methods for evaluating these in clinical trials.  For further
development beyond this award, collaboration and work through private
resources are encouraged.   Alternatively, the Group may request,
through the Collaborative Program Officer, that development be
assisted or sponsored by NIAID.  In the latter case the NIAID
Collaborative Program Officer will be available to facilitate or work
with the PI(s) on the analysis, summarization, preparation and
presentation of data to the appropriate NIAID staff and NIH advisory
committees (including the AIDS Research Advisory Committee) and other
working groups (such as the Animal Model Operating Committee or the
AIDS Vaccine Selection Committee).

o  Patent Coverage

Inasmuch as the development of effective AIDS vaccines is the
objective of this effort and since the active involvement by
industrial laboratories is facilitated by the existence of adequate
patent coverage, it is essential that applicants provide plans to
assure such coverage.  Each applicant Group that represents more than
one institution must, therefore, provide a detailed description of
the approach to be used for obtaining patent coverage and for
licensing where appropriate.  Applicants are encouraged to develop an
arrangement that is most suitable for their own particular
circumstances.  The NIAID will not be a partner in any patents or
royalties ensuing from this research.

Your attention is drawn to P.L. 96-517 as amended by P.L. 98-620 and
instructions published by the Office of Management and Budget in the
Federal Register (OMB Circular A-124), Volume 47, Number 34, Friday,
February 19, 1982, pp. 7556-7566.  Note that non-profit organizations
(including universities) and small business firms retain the rights
to any patent resulting from Government contracts, grants, or
Cooperative Agreements.  Also a Presidential memorandum of February
18, 1983 extended to all business concerns, regardless of size, the
first option to the ownership of rights to inventions as provided in
P.L. 96-517.

For those groups where it is appropriate (more than one institution),
the patent agreement, signed and dated by the organizational
officials authorized to enter into patent arrangements for each Group
member and member institution, should be submitted with the
applications and, prior to peer review, to Dr. Bonnie J. Mathieson at
the address listed under INQUIRIES).

Federal regulation clause 37 CFR 401 and HHS Inventions regulations
at 45 CFR Parts 6 and 8 require that NIH be informed of inventions
and licensing occurring under NIH funded research.  Invention and
licensing reports must be submitted to Extramural Invention Reports
office, Office of Extramural Research, Building 31, Room 5B41, NIH,
with a copy to Dr. Bonnie J. Mathieson at the address listed under
INQUIRIES.

It is standard policy that NIAID will retain the option to cross-file
or independently file an application for investigational clinical
trial; i.e., an Investigational New Drug Application (INDA) to the
United States Food and Drug Administration of any invention resulting
from these NIAID-supported Collaborative Projects.  Reports of data
generated by the Group or any of its investigators required for
inclusion in INDAs and Clinical Brochures and for cross-filing
purposes should be submitted by the Principal Investigator(s) to the
Collaborative Program Officer upon request.  Such reports will be in
final draft form and include background information, methods,
results, and conclusions.  They will be subject to approval and
revision by NIAID and may be augmented with test results from other
Government sponsored projects prior to submission to the appropriate
regulatory agency.

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 will be 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 should 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 should 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 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 Native Islanders,
Blacks, Hispanics).

The rational for studies on single minority populations 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 studies.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissue
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 the 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.

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 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.

LETTER OF INTENT

Prospective applicants are asked to submit, by April 15, 1993, a
letter of intent that includes a descriptive title, brief description
of the proposed research, the name, address, including institution,
telephone number (and FAX number, if available) of the Collaborative
Project Coordinator, the identities of the PIs and other key
personnel (with their institutions) participating in the
Collaborative Group, and the number and title of this RFA.

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 is helpful in planning for the review of expected
applications.  It allows NIAID staff to estimate the potential
workload for reviewers and to avoid possible conflict of interest in
the review process.

Since applications that do not address the objectives of the RFA will
be considered nonresponsive, potential applicants are strongly
encouraged to discuss their research plans with program staff before
completing their applications.

The letter of intent is to be sent to Dr. Bonnie J. Mathieson at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; 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; and from the NIH program administrator named below.

Detailed instructions for preparing the application are found in the
document "Preparation and Organization of a Collaborative Project
Application" that is included with the RFA.  Failure to follow these
instructions may result in an incomplete application which will be
returned to the Principal Investigator without review.

The R01 applications from a proposed Group that are sent to the
Division of Research Grants (DRG) must be submitted in one package.
In preparing the application, it is important that the points
identified under REVIEW CONSIDERATIONS are fulfilled.  The page
limitation requirements must be observed.  The collaborative nature
of the work should be discussed in the areas outlined in the
instructions for preparation of the application.  Additional NIAID
instructions for preparation of collaborative project applications
will be provided with the RFA.  Applicants may contact one of the
program administrators listed under INQUIRIES to seek clarification
and to discuss any questions related to this announcement.

The RFA label available in the  application form must be affixed to
the bottom of the face page of the 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.  In
addition, To assure the identification of the application with this
RFA the "Yes" box must be marked in item 2a of the face page of the
application form and "COLLABORATIVE MUCOSAL IMMUNOLOGY GROUPS FOR
AIDS VACCINES" (RFA 93-AI-08) typed.

Submit a  written original of the application, including the
Checklist, and three signed, 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 to DRG, also submit two exact complete
copies of your application directly to Dr. Diane Tingley at the
address listed under INQUIRIES. It is important to send these copies
at the same time as the original and three copies are sent to DRG.

Applications must be received by May 21, 1993. If an application is
received after that date, it will be returned to the applicant
without review.

REVIEW CONSIDERATIONS

Applications that have not followed the instructions for preparation
of the application or that  do not conform to the instructions
contained in the PHS 398 (rev. 9/91) application kit will be judged
incomplete and will be returned to the applicant.

Applications will be reviewed by DRG staff for completeness and by
NIAID staff to determine responsiveness to this RFA; those individual
or group applications judged to be incomplete or non-responsive will
be returned to the applicant without review.  A Group application
with a budget in excess of $500,000 total (direct and indirect) first
year costs will be returned without review unless the proposed amount
has been approved in advance by NIAID.  The application must be
directed towards the attainment of the stated programmatic goals (see
RESEARCH OBJECTIVES).

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 allow 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 on applications already reviewed, but such
applications must include an introduction addressing the previous
critique.

Those applications that are complete and responsive may be subjected
to a triage by a peer review group convened by DEA, NIAID to
determine their scientific merit relative to the other applications
received in response to this RFA.  The NIAID will remove from further
competition those applications judged to be noncompetitive for award
and will notify the applicant and institutional business official.

Those applications judged to be competitive for award will be further
reviewed for scientific and technical merit by a review committee
convened by the Scientific Review Branch, DEA, NIAID.  A second level
of review will be provided by the National Advisory Allergy and
Infectious Diseases Council during September 1993.  In the event of
multiple highly qualified applications, final funding recommendations
will be based on highest Program priorities.

Review Criteria

The following criteria will be used in the scientific review of
applications submitted in response to this RFA.

o  Scientific merit of the proposed individual projects including
innovation, originality, and feasibility of the approach;

o  The significance of the overall group goals and the development of
well-defined central research focus;

o  Evidence of collaboration, including the proportion of resources
devoted to collaborative studies (at least 30 percent);

o  Integration of the component R01s into a coherent,
multidisciplinary enterprise with adequate plans for collaboration,
interaction, and communication of information among participating
investigators.  The relationship of each project to the central focus
of the overall group;

o  Competence of the investigators to accomplish the proposed
research goals, their commitment, and the time they will devote to
the program.  While there is no maximum percent effort set, it is
anticipated that, due to the complexity and time required to maintain
a well-coordinated and productive collaborative research effort, a
minimum 15 percent (time) effort by each PI should be devoted to the
study, unless there is compelling evidence to the contrary that this
is not essential.

o  Accomplishments of the group to date (for investigators currently
involved in AIDS vaccine development research).

o  Environment in which the research will be conducted, including the
availability of space, equipment, animal facilities, and the
potential for interaction with active scientists in infectious
diseases, reproductive biology, virology and/or immunology from other
departments and/or institutions.

o  Arrangements for internal quality control of on-going research,
day-to-day management, internal communications and collaboration
among the investigators involved in the Group, contractual
agreements, and replacement of PIs, if required, on an interim or
permanent basis.

o  The appropriateness of the period of support and budget requested
in relation to the proposed program.

In addition the following criteria specific for this RFA will also be
considered by the review group:

o  Likelihood that new potential AIDS vaccines or vaccine strategies,
or that novel technical or methodological advances for vaccine
evaluation, will be identified during the course of the proposed
study;

o  Technical merit and appropriateness of proposed methods.

o  AWARD CRITERIA

Anticipated date of award is September 1993.  Awards will be made
based on:

o  Results of the initial scientific and technical merit review.

o  Significance and relevance to NIAID program goals in microbiology,
infectious diseases, allergy, immunologic diseases, and AIDS.

o  National needs and program balance.

o  Evidence and degree of collaboration in proposed work.

o  Policy and budgetary considerations, including availability of
funds.

INQUIRIES

It is essential that prospective applicants carefully review the RFA
and accompanying instructions on preparation of the application
before preparing an application.  The contacts listed below welcome
the opportunity to clarify issues or questions from potential
applicants.

Direct inquiries regarding programmatic issues and address the letter
of intent to:

Dr. Bonnie J. Mathieson
Division of AIDS
National Institute of Allergy and Infectious Diseases
Solar Building, Room 2B04
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-8200

Direct inquiries regarding scientific review matters to:

Dr. Diane Tingley
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C16
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-0818

Direct inquiries regarding fiscal matters to:

Ms. Jane Unsworth
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B22
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7075

Schedule

Letter of Intent Receipt Date:  April 15, 1993
Applications Receipt Date:      May 21, 1993

Council Date:                   September 1993
Earliest Award Date:            September 1993

AUTHORITY AND REGULATIONS

This program is described in the catalog of Federal Domestic
Assistance, 93.856 - Microbiology and Infectious Diseases Research
and 93.855 - Immunology, Allergy and Transplantation Research.
Awards are made under the authority 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 Part 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.

.

Return to RFAs Index

Return to NIH Guide Main Index

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)