Full Text AI-94-015

NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUPS FOR AIDS

NIH GUIDE, Volume 23, Number 15, April 15, 1994

RFA:   AI-94-015

P.T. 34

Keywords: 
  AIDS 
  Vaccine 


National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  May 31, 1994
Application Receipt Date:  August 19, 1994

PURPOSE

It is the intention of this Request for Applications (RFA) to
encourage investigators to collaborate on new approaches for Acquired
Immunodeficiency Syndrome (AIDS) vaccine research and development
through the National Cooperative Vaccine Development Groups (NCVDG)
Program, and to complement and balance the efforts presently being
pursued by existing NCVDGs.  It is recognized that the ultimate
objective of developing efficacious AIDS vaccines requires a solid
knowledge base of the immunology, virology, adjuvants, vectors and
delivery systems, molecular biology, and host interactions of
infectious agents.  The objective of this RFA is to stimulate
original, novel and innovative research of sound scientific
rationale, requiring comprehensive team effort, that is likely to
result in AIDS vaccines effective in prevention and/or used as
immunotherapy against AIDS.

The Vaccine Research and Development Branch, Division of AIDS, NIAID,
invites submission of applications aimed at the conceptualization,
development, and evaluation of vaccines designed to effectively
prevent AIDS.  This research should stress creative, novel approaches
to the development of effective AIDS vaccines and should have the
capacity to translate these concepts rapidly into improved candidate
vaccines.  The NCVDG can be focused in one or more vaccine areas and
may pursue studies of HIV-based vaccines or studies of relevant model
viruses (e.g., the Simian Immunodeficiency Viruses).  The Group must
possess the expertise necessary to conduct adequate evaluation of the
proposed approach(s) in preclinical situations.  Further studies
required for development of new vaccines to bring them to clinical
trial may be a part of the work proposed by an applicant.  An NCVDG
must form a cohesive team, and is encouraged to include scientists
from a combination of academic, non-profit research, and commercial
organizations.

Applications that include research projects from the private sector
(e.g., pharmaceutical, chemical, or biotechnological companies) are
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 RFA,
National Cooperative Vaccine Development Groups for AIDS (NCVDGs), 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, companies, units of State or local
governments, and eligible agencies of the Federal government.
Applications from minority individuals and women are encouraged.

MECHANISM OF SUPPORT

Awards will be made as multiproject cooperative agreements (U19s).
The multiproject cooperative agreement (U19) is an "assistance"
mechanism (rather than an "acquisition" mechanism) in which
substantial NIAID programmatic involvement with the recipient during
the performance of the planned activity is anticipated.  Essential
elements of the U19 mechanism include: (1) a minimum of three
inter-related research projects around a central theme; (2)
collaborative efforts and interaction among independent projects and
their investigators to achieve a common goal; (3) a single Principal
Investigator who will be scientifically and financially responsible
for the use and disposition of funds awarded; and (4) support
provided, as necessary, for "Core" resources or facilities, each of
which is expected to be utilized by at least two research projects in
order to facilitate the research effort.  Under the cooperative
agreement, the NIH purpose is to support and/or stimulate the
recipient's activity by involvement in and otherwise working jointly
with the award recipient in a partner role, but it is not to assume
direction, prime responsibility, or a dominant role in the activity.
Details of the responsibilities, relationships, and governance of a
study funded under cooperative agreement(s) are discussed later in
this document under the Section SPECIAL REQUIREMENTS -  Terms and
Conditions of Award.  The awardee will be responsible for the
planning direction, and execution of the proposed project and
interrelated activities.  While no maximum number of projects is
stipulated, it has been observed that when a multidisciplinary grant
or award exceeds six component projects the program becomes less
coordinated and more difficult to manage.

The total project period for applications submitted in response to
this RFA may not exceed four years.  Because the nature and scope of
the research proposed in response to this RFA may vary, it is
anticipated that the size of the award will vary also.

This RFA may be a one-time solicitation.  If, by the end of the third
year of the award, the NIAID has not announced its intent to re-issue
the RFA, incumbents should contact NIAID program staff and consider
submitting investigator-initiated (R01) applications which will
compete with all investigator-initiated applications and be reviewed
according to the customary peer review procedures.

While the number of applications cannot be determined, both new and
competitive renewal applications are anticipated and awards may be
from new grants and/or competing renewals.

All policies and requirements that govern the grant program of the
PHS, and the NIH apply.

FUNDS AVAILABLE

The NIAID anticipates making two awards for project periods up to
four years.  The NIAID has set aside $1.6 million total costs (direct
and indirect costs) for the first year of funding.  Estimated total
project costs (direct and indirect) over the four-year period will be
$6.6 million.  This level of support is dependent on the receipt of a
sufficient number and diversity of applications of high scientific
merit.  The sizes of resulting awards may vary. However, applications
with first-year budgets in excess of $1,000,000 total (direct and
indirect) should contact the NIAID Scientific Coordinator, at the
address listed under INQUIRIES, for written approval.  Budget
requests should be carefully justified and commensurate with the
complexity of the project.  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, and upon
satisfactory progress during the preceding years of the grant.

RESEARCH OBJECTIVES

Background

The National Institutes of Health and other agencies in the Public
Health Service are currently supporting extramural and intramural
projects to study the etiology, natural history, and demographics of
AIDS; to screen high-risk individuals; to determine means of
diminishing the risk of infection; and to develop vaccines and other
methods of prevention.  Notwithstanding these efforts, the rapidity
of the increase in diagnosed cases of AIDS and the morbidity from
this disease require the mobilization of the most creative scientific
talents -- regardless of their scientific discipline or
organizational affiliations -- into groups whose objective is to
pursue aggressively a concerted research effort to discover and
develop vaccines for preventing AIDS.  Based on recent surveillance
studies, the World Health Organization estimates that 13 million men,
women, and children worldwide have been infected with HIV.  Each day,
it is estimated that 5000 persons are newly infected.  By the year
2000, 40 million persons could be infected.  Moreover, more than 90
percent of these cases will be in developing countries.  It has been
estimated that all infected persons will progress to develop AIDS.

An NCVDG may consist of scientists from academic and/or non-profit
research institutions, and commercial organizations.  The NIAID has
awarded thirteen NCVDGs, some of which already have terminated.  The
purpose of this 1994 recompetition is to maintain the total NCVDG
network to ten Groups aimed at facilitating and accelerating efforts
in AIDS vaccine development.  A listing of the current NCVDGs may be
requested from program staff listed under INQUIRIES.

Research Goals and Objectives of the NCVDG Program

A.  The principal goal of the NCVDG Program for AIDS is the
conceptualization, development, and evaluation of vaccines designed
to effectively prevent the AIDS in humans.  This research can focus
on HIV or other lentiviruses (e.g., Simian Immunodeficiency Viruses)
that are appropriate models for AIDS vaccine development and that may
involve animal model studies of vaccine immunogenicity and efficacy.

B.  Applications for funding as an NCVDG should stress creative,
novel approaches to the development of effective AIDS vaccines and
may emphasize one or more of the general approaches outlined below.
It is important to have the ability to perform immunological analyses
to evaluate the work being done, and to network with the NIAID
Adjuvant Group and the NIAID Collaborative Mucosal Immunology Groups.
Since the currently funded NCVDGs are also pursuing research in many
of these areas, potential applicants are strongly encouraged to
contact program staff to determine if their proposed studies address
vaccine strategies not currently being funded.  Applications for
research on novel vaccine vectors, immunogen processing and
presentation, mucosal immunity, nucleic acid vaccines and creative
methods to enhance immunogenicity are encouraged.

Approaches may include, but are not limited to:

1. live attenuated vaccines;
2. whole inactivated vaccines;
3. recombinant proteins or protein fragments;
4. novel recombinant viruses or other vectors (e.g., yeast Ty
elements, hepatitis B virus, bacteria);
5. synthetic peptides;
6. combination approaches;
7. DNA immunization.
8. There are also unique opportunities for adaptation of existing
pediatric vaccines to express HIV/SIV antigens.  Development of such
vaccines for production and testing in neonatal animals for eventual
pediatric intervention in high risk births is encouraged.

C.  Applications should address all aspects of research, from basic
research to subsequent developmental studies, scale-up and
production, evaluation in laboratory animals, protection of
appropriate species from infection or disease following virulent
challenge, and other considerations that relate to the acceptability
and utility of candidate vaccines for clinical trials.

Applicants should describe their plans to accommodate the stated
program requirements, to address each of the review criteria, and to
ensure adequate staff involvement.

D.  The Group's objectives and goals should be relevant and
compatible with NIAID program's missions and directions as stated in
this RFA.

E.  For small pilot studies, the Principal Investigator is expected
to have access to a small number of animals and to primate
facilities.

F.  The applicant institution and the Principal Investigator will be
responsible for the Group's application.  The award will be made to
the applicant institution on behalf of the Group as a whole and not
to individual research projects within the Group.  The applicant
institution will provide a Central Operations Office for the Group,
will be responsible for the performance of the entire Group, and will
be accountable for the funds awarded.

SPECIAL REQUIREMENTS

A.  Minimum Requirements for NCVDG Application

All applications must consist of at least three interrelated projects
focusing on a unifying central theme.  A minimum 10 percent (time)
effort by the Principal Investigator and each Project Leader should
be devoted to the study, and five percent effort will be considered a
minimum for core leaders, unless there are compelling arguments to
the contrary.

Meetings

a.  Two mandatory Group meetings.  The Principal Investigator and
Project Leaders of the Group, and the NIAID Scientific Coordinator,
will meet twice per year to review progress, plan and design research
activities, and establish priorities within the Group.  The Principal
Investigator will be responsible for scheduling the time and place
(generally at one of the performance sites) and for preparing concise
proceedings or minutes, which will be delivered to the members of the
group within sixty days of the meeting.  The agenda for this meeting
will be determined by agreement between the Principal Investigator
and the NIAID Scientific Coordinator.  NIAID staff may not chair
Group meetings.

b.  One mandatory meeting of the awardees will be held annually at
the NIH or at a site designated by the NIAID during which the
Principal Investigators and Project Leaders of all the Groups will
present significant findings in symposium format.

Applicants should include requests for travel funds specifically for
the above meetings when they prepare their budgets.

c.  Informal meetings.  A critical determinant of Group success will
be the degree of communication among its members.  Therefore, in
addition to the three meetings listed above, two additional meetings,
which may be necessary for coordination of Group activities, may be
scheduled if justified and should be included in the budget.  Regular
telephone and written communication will be important and are
encouraged.

B.  Definitions

COOPERATIVE AGREEMENT - An assistance mechanism in which substantial
NIAID programmatic involvement with the recipient organization during
the performance of the planned activity is anticipated.

NATIONAL COOPERATIVE VACCINE DEVELOPMENT GROUP (NCVDG) - In this RFA
the terms National Cooperative Vaccine Development Group, NCVDG, and
"Group" are synonymous.  Each Group may be composed of a number of
scientific investigators from academic and/or non-profit research
institutions as well as scientists from commercial organizations,
performing research on interrelated projects whose central focus is
development of vaccine(s) for AIDS.

RESEARCH PROJECT - A discrete, specified, circumscribed project that
must relate to the overall theme of the NCVDG.

SCIENTIFIC CORE COMPONENTS- Facilities for equipment and services
that are shared by two or more projects of the Group.  Examples of
Scientific Core components are:  vaccine production facility, reagent
production, animal model evaluations.  The Scientific Core can be
defined as a component with established techniques and assays that
perform a service function resulting in an economy of effort and
savings in the overall costs.  The Scientific Core unit is to be
described in the same detail as research projects to enable the
evaluation of its scientific expertise and technical merit.  (See
details for preparation of the budgets under "PREPARATION AND
ORGANIZATION OF THE APPLICATION).

ADMINISTRATIVE CORE - An administrative facility that provides
central operations and support for the overall management of the
cooperative agreement and services shared by the Group as a whole.
The Administrative Core should have a budget separate from that of
the Principal Investigator's, but administered by the Principal
Investigator's organization.

PROJECT LEADER - The leader of one of the scientific research
projects of the NCVDG, who is responsible for the scientific conduct
of that project.

CORE LEADER - The leader of one of the Scientific or Administrative
Cores of the NCVDG

PRINCIPAL INVESTIGATOR - The person who assembles the NCVDG, who is
responsible for the performance of the Group as a whole and for that
of each of the Project Leaders, and who submits the single
application in response to this RFA.  The Principal Investigator will
coordinate Group activities scientifically and administratively and
should preferably also be project leader of one of the Research
Projects of the Group.  The awardee institution establishes and
operates the Central Operations Office that funds Group members and
is legally and fiscally accountable for the disposition of funds
awarded.  While the Principal Investigator need not be an employee of
the awardee institution, for this Program the NIAID strongly prefers
that the Principal Investigator be an employee of the awardee
institution.

NIAID SCIENTIFIC COORDINATOR - A scientist on the extramural staff of
the NIAID who functions as a peer with the Principal Investigators
and Project Leaders and facilitates the partnership relationship
between NIAID and the Groups.

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

ARBITRATION PANEL - A panel that is formed to review any scientific
or programmatic activity that is impeding progress within a Group.
It will be composed of a "Group" designee, one NIAID designee, and a
third designee with expertise in the relevant area and chosen by the
other two. Such panels may help resolve both scientific and
programmatic issues that develop during the course of work that
restrict progress.

C.  Patent Coverage

Inasmuch as the development of effective AIDS vaccines is the
objective of this effort, and since active involvement by industrial
laboratories is facilitated by the existence of adequate patent
coverage, it is essential that applicants provide plans to ensure
such coverage.  Since several institutions may be involved, the
situation could be complicated.  Each applicant Group must,
therefore, provide a detailed description of the approach to be used
for obtaining patent coverage and for licensing where appropriate, in
particular where the invention may involve investigators from more
than one institution.  In addition, each Group must provide a
detailed description of the procedures to be followed for the
resolution of legal problems that may develop.  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. As a
result of this memorandum, the relationships among industrial
organizations and other participants are simplified, since all Group
members can now be full partners in the research and in any
inventions resulting therefrom.  The specific patenting arrangements
among the institutions may vary, and could include joint patent
ownership, exclusive licensing arrangements, etc.  Applicants are
encouraged to develop an arrangement that is most suitable for their
own particular circumstances.

The patent agreement, signed and dated by the organizational
officials authorized to enter into patent arrangements for each Group
member and member institution, must be sent prior to peer review to
Dr. Alan Schultz, Vaccine Research and Development Branch, Division
of AIDS, NIAID, Solar Building Room 2B-01, 6003 Executive Boulevard,
Bethesda, MD  20892.  (For express mail or courier services, the
address is Rockville, MD 20852.)

Federal regulation clause 37CFR401 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 the Extramural Invention
Reports office, Office of Extramural Research, Building 31, Room
5B41, NIH, with a copy to Dr. Alan Schultz, Vaccine Research and
Development Branch, Division of AIDS, NIAID, Solar Building Room
2B-01, 6003 Executive Boulevard, Bethesda, MD 20892.

D.  Terms and Conditions of Award

NOTE:  Failure to abide by any of the Terms of Award pertaining to
awardee responsibilities stipulated in this Section may result in the
withholding of funds by the NIAID until compliance with the Terms is
restored.

Working Relationships Within a Cooperative Agreement

Under the Cooperative Agreement, a partner relationship exists
between the recipient of the award and the NIAID in which the Group
is responsive to the requirements and conditions set forth in this
RFA.  The participation of the Government through the NIAID
extramural staff is intended to facilitate, but not to direct, a
concerted effort by all members of the network of Groups by providing
appropriate scientific input, by coordinating efforts among Groups,
by making available to Groups biological materials for testing, by
accessing appropriate data bases, and by providing ancillary testing
and other resources, such as reagents, samples or experimental
animals, which are available under existing Government contracts.
The interaction of academic and non-profit research institutions with
commercial organizations and the Government is strongly encouraged
and is expected to favor expeditious preclinical development of AIDS
vaccines to prevent transmission of HIV.

1.  Awardee Rights and Responsibilities:

The Principal Investigator defines the details for the project within
the guidelines of the RFA, retains primary responsibility for the
performance of the scientific activity, and agrees to accept close
assistance in coordination, cooperation, and participation of NIAID
staff in all aspects of scientific and technical management of the
project in accordance with the terms formally and mutually agreed
upon prior to the award.  The responsibility for the planning,
direction, and execution of the proposed project will be solely that
of the applicant.

A.  Two mandatory Group meetings.  The Principal Investigator and
Project Leaders of the Group, and the NIAID Scientific Coordinator,
must meet twice per year to review progress, plan and design research
activities, and establish priorities within the Group.

B.  The Principal Investigator will be responsible for the timely
submission of all abstracts, manuscripts and reviews (co)authored by
members of the Group and supported in part or in total under this
Agreement.  The Principal Investigator and Project Leaders are
requested to submit manuscripts to the Scientific Coordinator within
three weeks of acceptance for publication so that an up-to-date
summary of program accomplishments can be maintained.

C.  Publications or oral presentations of work done under this
Agreement is the responsibility of the Principal Investigator and
appropriate Project Leaders and will require appropriate
acknowledgement of NIAID support.

D.  While the NIAID Scientific Coordinator has a right of access to
the data (see NIAID staff responsibilities below) the applicant will
retain custody of and rights to the data.  Timely publication of
major findings is encouraged.

2.  NIAID Staff Responsibilities:  Nature of NIAID Participation

Assistance via a Cooperative Agreement differs from the traditional
research grant in that, in addition to the normal programmatic and
administrative stewardship responsibilities, the awarding component
(NIAID) anticipates substantial programmatic involvement during
performance of the research program.  The NIAID shall work with the
Group and shall be represented by a NIAID Scientific Coordinator.
The coordinator shall be a member of the professional staff of the
Vaccine Research and Development Branch, Basic Research and
Development Program, Division of AIDS.

During performance of the award, the NIAID Scientific Coordinator may
provide appropriate assistance, advice, and guidance by:
participating in the design of Group activities; advising in the
selection of sources or resources (e.g. determining where a
particular reagent can be found); coordinating or participating in
collection and/or analysis of data; advising in management and
technical performance; or participating in the preparation of
publications.  However, the role of NIAID will be to facilitate and
not to direct the activities.  It is anticipated that decisions in
all activities will be reached by consensus of the Group and that
NIAID staff will be given the opportunity to offer input to this
process.  The manner of reaching this consensus and the final
decision-making authority will rest with the Principal Investigator.

1.  NIAID Participation in Design of Group Activities, Development of
Research Protocols and Evaluation of Results

a.  The NIAID Scientific Coordinator, like other Group members, may
suggest studies within the scope of the Group's objectives and
research activities; may present to the Group experimental findings
from published sources or from contract projects in support of these
suggestions; may participate in the design, but not in the execution,
of experiments agreed to by the Group; and may participate in the
analysis of results.

b.  The NIAID Scientific Coordinator may assist the Group or other
individual members in research planning, particularly by:

1)  provision of needed resources and information that may not be
otherwise be available to the Group;

2)  provision of information concerning work being conducted in other
NIAID-supported extramural projects, in order to reduce or prevent
duplication of efforts.

2.  NIAID Participation in Collection and Analysis of Data,
Procedures for Submission of Results to NIAID, and Preparation of
Group Findings for Presentation and Publication

In addition to the special reports and stipulations described below,
reporting requirements will be identical to those currently in
existence for awardees of traditional NIH research project grants.

a) The principal end product of NCVDG activities will be the
development of promising AIDS vaccines for testing in clinical
trials.  Subsequent developmental work through private resources is
encouraged.  Alternatively, the Group may recommend that development
be sponsored by the NIAID.  In the latter case, it will be necessary
for the Principal Investigator (s), appropriate Project Leaders and
the NIAID Scientific Coordinator to collaborate in the analysis,
summarization, preparation, and presentation of data to the
appropriate NIAID staff and NIH advisory committees (including the
AIDS Research Advisory Committee and NIAID Council) and other working
groups (such as the Animal Model Operating Committee or the AIDS
Vaccine Selection Committee).

b) 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 Cooperative Agreements.  Reports of data generated by the
Group or any of its members required for inclusion in INDA's and
Clinical Brochures and for cross-filing purposes will be submitted by
the Principal Investigator to the Scientific Coordinator 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 the NIAID and may be augmented
with test results from other Government sponsored projects prior to
submission to the appropriate regulatory agency.

c) The NIAID, via the NIAID Scientific Coordinator, will have access
to data generated under this Cooperative Agreement.  Information
obtained from the data may be used by the NIAID Scientific
Coordinator for the preparation of internal reports on the Group's
activities.

3.  Arbitration Process

Inasmuch as certain activities require approval by NIAID staff during
performance of this Cooperative Agreement, specifically, reports
intended for inclusion in INDA's and Clinical Brochures,
redistribution of biological materials received from the Government,
and dissemination of research findings resulting from the use of
these materials, NIAID will establish an arbitration process to
resolve any differences of opinion between the awardee and the NIAID
on scientific-technical matters.  An arbitration panel, composed of
one Group designee, one NIAID designee, and a third designee with
expertise in the relevant area and chosen by the other two, will be
formed to review any scientific or programmatic issue that is
significantly restricting progress.  These special arbitration
procedures in no way affect the awardee's right to appeal an adverse
action in accordance with PHS regulations at 42 CFR Part 50, Subpart
D, and HHS regulations at 45 CFR Part 16.

The special "TERMS AND CONDITIONS OF AWARD: NATURE OF NIAID
PARTICIPATION" described in this Section are in addition to, and not
in lieu of, otherwise applicable OMB administrative guidelines, HHS
grant administration regulations at 45 CFR Parts 74 and 92, and other
HHS, PHS, and NIH grant administration policies.

STUDY POPULATIONS

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 subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990. The new policy contains some
provisions that are substantially different from the 1990 policies.

All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 9, 1994 (FR 59 11146-11151) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.

Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by May 31, 1994, a letter
of intent that includes a descriptive title of the overall proposed
research; the name, address, telephone number, and institution of the
Principal Investigator; names of prospective project leaders and
other key investigators and their respective institutions; title,
project leader, and institution for each component research project,
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 applications, the information that it
contains is helpful in planning for the review of applications.  It
allows NIAID staff to estimate the potential review workload and to
take early steps to avoid conflict of interest in the review.

The letter of intent is to be sent to Dr. Dianne Tingley at the
address listed under INQUIRIES.

APPLICATION PROCEDURES

Preparation and Organization of the Application: Special Instructions
for Preparing the Group Application

General Instructions:  Overall Application

For preparing the NCVDG application this Section supplements the
instructions found in form PHS 398 (rev. 9/91).  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 Information, Division of Research Grants,
National Institutes of Health, Westwood Building, Room 449, Bethesda,
MD 20892, telephone 301/710-0267.  Additional instructions are
required because the form PHS 398 is designed primarily for
individual research grant (R01) applications, whereas the Group
application consists of several research projects interrelated by a
common theme.  Items that require modification for multi-project
applications, in addition to other information not requested in form
PHS 398, are detailed below:

PHS 398 Instructions - Pages 1-10:  General Information and  General
Instructions.  No modification.

PHS 398 Instructions - Pages 10-16: Specific instructions for filling
Form page 1 (Face Page of Form 398) of the application.

Page 1 of Form PHS 398

Complete items 1 through 18 as instructed.  Please note that this
should be Page 1 of the entire application; all succeeding pages
should be numbered consecutively.  Since the application is in
response to an RFA, mark the "YES" box in item 2a and enter the RFA
number and the title of this RFA.

For item 3a to 3h, enter the name of the Principal Investigator of
the Group along with other required information concerning him or
her.  The applicant (awardee) institution and the Principal
Investigator will be responsible for the application, for Group
research activities, and the awardee institution will be responsible
for the support of Group activities through a Central Operations
Office.

For item 11, name the applicant organization and its address.  The
applicant organization (awardee institution) will provide the Central
Operations Office and be legally and financially responsible and be
accountable for the use and disposition of funds awarded on the basis
of this RFA; show availability of personnel and facilities capable of
performing and supporting the administrative functions of the Group.

Page 2 of Form PHS 398 - This section represents an abstract of the
overall program.  It should briefly state the overall goals of the
NCVDG and give an indication of the research emphasis of component
projects and cores.  Do not exceed space provided.  This section
should be written in such a manner that it can be adapted by NIH
staff to be the Overall Description portion of the Summary Statement.

Under "Key Personnel Engaged on Project," list the Principal
Investigator of the overall NCVDG and the Project Leader for each
component project and the Core Leader for each core.

Page 3 of Form PHS 398: Table of Contents ( - Modification necessary)

The NCVDG application should be assembled and paginated as one
complete application.  Following the complete table of contents for
the entire document, the applicant should provide a separate table of
contents for each project similar in detail to the table of contents
in the PHS 398.  Bearing in mind that the application will be
reviewed project by project and core by core, prepare a detailed
table of contents that will enable reviewers to readily find specific
information.  A page reference should be included for the budget that
is associated with each project/core.  Further, each project should
be identified by number, title and responsible Project Leader.

Summary Budget Information Required for the Group Application.

Summary budgets should be prepared for the total Group application.

a.  Present a composite budget for the first year according to the
format shown in Table I in Appendix II of this RFA.

b.  Use page 5 from the PHS Form 398 to prepare a summary budget by
category for all years of requested support.  Requests for unusual
increases in any of the succeeding years must be justified in the
individual project budgets.

c.  Detailed budgets for each category for each research project and
each core are requested for the first year only.

Personnel

List all professional and non-professional participants (including
those with no salary requested) in the Group for the first year of
requested support utilizing the format shown in Table II and the
distribution of professional effort (%) for other support as shown in
Table III.  Sample tables labeled I, II, and III are found in
Appendix II, available from the program staff listed under INQUIRIES.

Page 6 of Form 398:  Biographical Sketches

Prepare biographical sketches for all professional personnel
participating in individual projects and cores, using page 6 of the
Form PHS 398 application kit and applying the same page limitations.
The biographical sketches, with that of the PI first and those of the
other key professional personnel following in alphabetical order,
should be placed at the end of the application, appropriately
numbered and referenced in the table of contents.

Research Plan

As an introduction to the component elements of the NCVDG provide the
information detailed below, using continuation pages as needed.  Name
this section "OVERALL PROGRAM".  Since this Section will constitute
the Research Plan for the overall program a total of up to 25 pages
may be used in its presentation (Introduction, Organizational and
Administrative Structure).  The Facilities pages should not be
included in the 25-page limitation.

1.  Program Introduction - Statement of Objectives  The NCVDG should
be viewed as a confederation of interrelated research projects --
each capable of standing on its own scientific merit, but
complementary to one another and focused on a common theme.  It is
very important to establish the programmatic theme in the first few
sentences of a general introduction.

The introduction is an important section, for it provides the
investigator an opportunity to give conceptual wholeness to the
overall program -- by giving a statement of the general problem area
and by laying out a broad strategy for attacking the problems.  As
the strategy develops, each project and core should be cited briefly
as to its place in the overall scheme.

The introductory section should briefly state the rationale of the
research proposed in each project describing how it relates to
vaccine development and/or the anticipated approach to achieve and/or
evaluate the work proposed.

It is essential to demonstrate that each component research project
contributes to the attainment of the Group's objectives and that each
has available the professional and technical personnel to permit
efficient and successful conduct of the proposed research; i.e., it
is important to show that the total personnel of the Group are
sufficient in quality and quantity to assure successful conduct of
the proposed research.

It is useful to provide a clear, concise plan in narrative and
diagrammatic form that depicts the interrelationships among the
members of the NCVDG and the contribution of each to fulfillment of
Group objectives; provide an organizational chart of the NCVDG
showing the name, organization, and scientific discipline of the
Principal Investigator and Project Leaders; provide an organizational
chart for each project and core within the Group showing
relationships among the key personnel.

To assure the maintenance of close collaboration and effective
communication among members of the Group include letters of
commitment to this plan and also a letter accepting the participation
of the NIAID Scientific Coordinator, defined under TERMS AND
CONDITIONS OF AWARD.

It is also appropriate in this section to indicate the prior
collaborative arrangements between investigators in the Group.  It is
important to reveal the anticipated unique advantages to be expected
from the Group operating within the proposed collaborative efforts;
how the projects are mutually reinforcing; and how collectively they
will further the stated goals of the proposed research.

NOTE:   The Principal Investigator should provide a narrative,
supported by diagrammatic presentation(s) as needed, addressing the
points raised under the above items.  This description should clearly
demonstrate the interactive, cooperative, integrated and
interdependent nature of each proposed project and core to the Group
activities as a whole.  The narrative is to be included under the
Administrative Core:  it will serve as one of the criteria used by
the peer review group to evaluate and rate the ability of the
Principal Investigator to assemble a comprehensive, interactive
Group.

2.  Facilities: use  page 8 of PHS form 398, using continuation pages
as necessary

Demonstrate that each component laboratory project, Scientific Core
facilities, and the NCVDG as a whole have available the facilities
required for conduct of the proposed research; demonstrate that
appropriate biohazard facilities and safety procedures are in place
for activities involving HIV or SIV and other pathogens and pathogen-
producing cell lines as outlined in The Federal Register, Volume 49,
Number 201, Tuesday, October 16, 1984, p. 40556; include a
description of the Institutional Safety Guidelines and approval
procedures for each proposed laboratory project. This information
should be conveyed on page HH of the PHS 398 under Resources and
Environment.

3.  Organizational and Administrative Structure

a.  Organizational and Administrative Structure of the NCVDG

Describe in detail and by diagram the chain of responsibility for
decision-making and administration beginning at the level of
Principal Investigator and including the different research project
leaders and core leaders.  Indicate where in the chain of
responsibility advisory groups (local or outside consultants) will be
used. Describe their role in establishing quality control of the
research efforts.  This information is to be provided in the
Administrative Core.

b.  Consortium Arrangements

If an application includes research activity involving institutions
other than the sponsoring organization, the program is considered a
consortium effort.  Such activity may be included in a
multi-component (such as a U19) application, but it is imperative
that care be taken in preparing any consortium application so that
the programmatic, fiscal, and administrative considerations are fully
explained.  The policy governing consortia is  described in the NIH
Guide for Grants and Contracts (Vol.  14, No. 7, June 21, 1985),
which should be available at your institution's business office, or
use the Office of Grants Information publication entitled,
"Guidelines for Establishing and Operating Consortium Grants,"
January 1989, which may be obtained by calling 301-710-0267.  These
guidelines should be read carefully before such an application is
developed.  If clarification of the  guidelines is needed, the
applicant is encouraged to contact grants management staff, Ms. Carol
Alderson at 301-496-7075.

c.  Patent Coverage

Provide a description of the Group's plan for assuring adequate
patent coverage of new inventions that may issue as a result of
Government funding of this U19.

NOTE:  A formal statement of Patent Agreement among all Group members
and their institutions as well as a detailed description of
procedures to be followed for the resolution of legal problems which
may develop, signed and dated by the organizational official
authorized to enter into patent arrangements for each Group member
and member institution, is to be submitted to Dr. Alan Schultz (for
Dr. Schultz's complete address see INQUIRIES", below.)

Core Units

Since the cores are designated to provide resources for 2 or more of
the component research projects, all pages on cores should be part of
the "OVERALL Program."

1.  Use letters to designate individual core units and give each a
title.

2.  Provide the name and academic title of the core leader and key
participating investigators.

3.  Administrative Core: The Administrative Core component should be
at the awardee Institution and should provide BOTH travel funding
for: [a] personnel to participate in two required annual intra-Group
meetings, and any additional justified intra-Group meetings, [b]
Principal Investigator and project/core leaders for a NIAID-specified
annual U.S. meeting with NCVDG Principal Investigators and
project/core leaders of other Groups; AND other funding including
secretarial and/or administrative services, expenses for Group
publications and communication expenses such as conference calls,
facsimiles, and postage.

4.  Description of Scientific Core(s):  Describe the role and
importance of the core as a resource to the NCVDG as a whole and
indicate the specific projects it will serve, e.g., production of
monoclonal antibodies and distribution to research projects 1, 2, and
4.  This section should present a clear picture of the facilities,
techniques, and professional skills that the core will provide. The
role of the core leader and each of the key participants should be
described.  Each core request should include a chart which apportions
the dollars, or percentage of dollars, that will be required to
support each component research project which will use the resource.
(See Table IV in Appendix II of this RFA).

For presentation of each Core budget request and justifications the
following form PHS 398 pages should be used:

o  Cover Page.  Using PHS 398 page AA type the title of the Core on
the upper left hand margin and enter a descriptive name of the
requested core (e.g., Administrative Core, Monoclonal Antibody
Production Core) in item 1, Title of Project.  Complete data items 3a
(Name of Core Leader), 4, 5, 6, 7, 8, and 9.

o  Pages 4 and 5:  Budget for Core(s): Fill these pages for each core
request, providing justifications with the same detail as in research
projects.

o  The budget for each core unit should be presented according to the
instructions indicated on pages 16-19 of the form PHS 398
Instructions.  A detailed budget is required for the first year (form
PHS 398, page 4) and a  budget summary for all additional years (form
PHS 398, page 5).  Explicit detailed budget justifications for all
years should be included.  Budget pages should be clearly labeled so
that they can be accurately associated with the individual cores.

o  Other activities that are essential to maintaining or achieving
the objectives of the stated research projects (e.g., large scale
production of reagents, animal maintenance) should be included as
subcontracts under the budget for the Scientific Core.

Individual Research Projects

1.  General Information.

The strength of the multiproject application will be judged on the
basis of the research it will support.  Therefore, the reviewers will
expect each project and core unit to be described in the same detail
as for a regular research grant application to enable the scientific
merit to be judged from the written application.

2. Format for Presentation of Individual Research Projects  Each
project leader should present his or her individual project using the
form PHS 398 (rev. 9/91) and following the application kit
instructions, except as modified below.

o  Cover Page   Using page AA of form PHS 398, complete items 1, 3a,
3d, 4, and 5 ONLY.  In item 1, enter Project Number and a descriptive
project title.  In items 3a and 3d, enter the name and academic title
of the project leader.  Items 4 and 5 are self-explanatory.

o  Page 2 of form PHS 398.  Provide an abstract of the research
proposed in the project.  Prepare the abstract according to the
instructions provided on page 2 of PHS Form 398.  This abstract
should be written in such a manner that it could be adapted by NIH
staff to constitute the Description portion of the project in the
Summary Statement.

o  Pages 4 and 5 of Form PHS 398.  Detailed first year budget and
budget for entire project period: follow instructions on pages 16-19
of the Form PHS 398 instructions.  The budget pages should have the
project number and the project leader's name in the upper left hand
of each budget page.

o  Page 7 of Form PHS 398: Other Support:  FOLLOW INSTRUCTIONS
CAREFULLY.  If a duplicate R01 or R29 is submitted concurrently or is
pending, it should be so stated in this section.  Incomplete,
inaccurate or ambiguous information about OTHER SUPPORT, whether
active or pending, may lead to delays in the review of the
application.

3.  Research Plan:  Follow the instructions indicated in IV. C.,
pages 19 through 22 of the PHS Form 398 Instructions, completing
items 1 through 4 in detail.  In addition, attention should be given
to integration of the component project into the overall Group
project.  As with a regular research grant application, the overall
research plan for each project should not exceed 25 pages (from
Specific Aims through Research Design and Methods).  The following
points should be addressed in the appropriate sections.

o  Specific Aims:  In addition to listing the specific objectives for
the total period of requested support for the component, state the
overall objective or long-term goal of the research and its
relationship to the goals of the NCVDG and how it relates to other
projects or cores in the Group.

o  Significance:  In addition to the overall biological significance
of the proposed research, this section should indicate the relevance
of the project to the primary theme of the NCVDG.

o  Collaborative Arrangements:  Describe the collaboration between
investigators in this project and other investigators within the
NCVDG.  Describe in detail any other collaborative arrangements
anticipated, either  internal or external to the institution.
Include letters from collaborating investigators indicating their
agreement with the collaborative arrangements.

Submission 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 Information, Division of
Research Grants, National Institutes of Health, Westwood Building,
Room 449, Bethesda, MD 20892, telephone 301/710-0267.

The RFA label available in the PHS 398 (rev. 9/91) 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 your
application with this RFA the "YES" box must be marked in item 2a of
the face page of the application form and the title and number of
this RFA typed.

Applications that are not received as a single package from the
Principal Investigator and 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.

Submit a signed, typewritten original of the application, including
the Checklist, and three signed photocopies of the application, in
one package to:

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

At the time of submission, also submit two exact copies of the
application and five sets of the appendix and reprints directly to:

Dr. Dianne Tingley
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C-16
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-0818

Applications must be received by August 19, 1994.  If an application
is received after that date, it 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, 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.
This restriction is superseded by an NIH policy permitting concurrent
submission of a duplicate R01 and a component of a multiproject
application.  The NIH policy however, further stipulates that should
both the R01 and the multi-project application be considered for
funding, the R01 will be relinquished in favor of the multi-project
application.

REVIEW CONSIDERATIONS

A.  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.

Applications with budgets in excess of $1,000,000 total (direct and
indirect) first year costs, which do not have the written approval of
the program contact (see INQUIRIES) will be returned without review.
Those applications that are complete and responsive may be subjected
to a triage by an NIAID peer review group to determine their
scientific competitiveness 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, Division of Extramural
Activities.  A second level of review will be provided by the
National Advisory Allergy and Infectious Diseases Council.  In the
event of multiple highly qualified applications, final funding
recommendations will be based on highest program priorities.  Review
date, Council meeting date, and earliest award date are stated in
Schedule, below.

B.  Review Criteria

The application must be directed towards the attainment of the stated
programmatic goals (see RESEARCH OBJECTIVES).  The following factors
are the criteria used by peer review groups in the scientific and
technical review of multicomponent applications:

General Review Criteria

o  The scientific merit of the program as a whole, as well as that of
each individual project.  Each project must be supportable on its own
merit.

o  The significance of the overall program goals and the development
of a well-defined central research focus.

o  Scientific gain achieved by combining the component projects into
a multiproject program, beyond that achievable if each project were
to be pursued independently.

o  The cohesiveness and multidisciplinary or multifaceted scope of
the program and the coordination and interrelationships among the
individual projects and core(s).

o  The justification and usefulness to the various research projects
of the core facilities.  The relationship of each core to the central
focus of the overall program.  Each core unit must provide essential
facilities or service for two or more approved individual projects.

o  The leadership, scientific ability, and administrative competence
of the Principal Investigator for the development, implementation,
and management of a comprehensive research program with the defined
central research focus; and the Principal Investigator's commitment
to devote adequate time and effort to the program.

o  The qualifications, experience, and commitment of the
investigators responsible for the individual research projects or
core(s) (Project/Core Leaders) and their contribution to the program,
including their ability to devote adequate time and effort to the
program.  It is anticipated that, due to the complexity and time
required to maintain a well-coordinated and productive research
effort, a minimum 20% (time) effort by the Principal Investigator and
each Project Leader should be devoted to the study, unless there are
compelling arguments to the contrary.

o  Accomplishments of the program to date (for renewal applications),
and research experiences and accomplishments of investigators in the
Group in the research areas outlined in the RFA (for new
applications).

o  The academic and physical environment in which the research will
be conducted, including the adequacy of space, equipment, animal
facilities, biohazard containment facilities; and the potential for
interaction with active scientists in disciplines including
infectious diseases, reproductive biology, virology, molecular
biology and/or immunology from other departments and/or institutions.

o  A sound institutional administrative and organizational structure
that facilitates attainment of the objective(s) of the program,
including fiscal responsibility and management capability to assist
the PI and staff in following PHS policy.

o  Arrangements for internal quality control of on-going research,
allocation of funds, day-to-day management, internal communications
and cooperation among the investigators involved in the program,
contractual agreements, and replacement of the Principal
Investigator, or other key personnel if required, on an interim or
permanent basis.

o  Management of the ethical and hazardous aspects of the project(s).

Specific Review Criteria

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

o  Documented commitment of Institutions represented by Group
members; documented capability of Principal Investigator's
Institution to serve as the Central Operations Office for the Group;
willingness to accept the participation of the NIAID Coordinator.

o  Likelihood that new strategies and vaccine approaches will be
identified during the course of the proposed study which may have
relevance to the prevention of AIDS in humans.

AWARD CRITERIA

Award criteria will be based on scientific merit as reflected in the
priority score, program priorities, and the availability of funds.

INQUIRIES

The opportunity to clarify issues or questions about the RFA from
potential applicants is welcome.  Direct inquiries regarding the RFA
and programmatic issues to:

Alan Schultz, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
Solar Building, Room 2B-01
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-8200
FAX:  (301) 402-1506

Direct letters of intent, and inquiries regarding application
preparation and review to:

Dianne Tingley, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C-16
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-0818

Direct inquiries regarding fiscal matters to:
Ms. Carol Alderson
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B-27
6003 Executive Boulevard
Bethesda, MD  20892
Telephone:  (301) 496-7075

Schedule

Letter of Intent Receipt Date:  May 31, 1994
Application Receipt Date:       August 19, 1994
Scientific Review Date:         November 1994
Council Meeting Date:           February 22, 1995
Earliest Award Date:            April 1, 1995

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 grant policies and
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.  This
program is not subject to the intergovernmental review requirements
of Executive Order 122372 or Health Systems Agency review.

The Public Health Service (PHS) strongly encourages all grant
recipients to provide a smoke-free workplace and promote the non-use
of all tobacco products.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American
people.

.

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