Full Text AI-93-04


NIH GUIDE, Volume 22, Number 3, January 22, 1993

RFA:  AI-93-04

P.T. 34


National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  February 26, 1993
Application Receipt Date:  April 22, 1993


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, 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 National Institute of Allergy and Infectious Diseases (NIAID)
invites 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 (SIV)).  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. Alternatively, an NCVDG
may request that the NIAID conduct these developmental tasks using
contracts now in place (SIV Evaluation Units, Chimpanzee Access via
Interagency Agreement with the National Cancer Institute, and AIDS
Resources and Reagents Contract).  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


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, 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).


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 and
local governments, and eligible agencies of the Federal government.
Applications from minority individuals and women are encouraged.


Awards will be made as cooperative agreements (U01s).  The
cooperative agreement is an assistance mechanism in which substantial
NIAID programmatic involvement with the recipient during the
performance of the planned activity is anticipated.  The nature of
NIAID staff participation is described in 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.  A minimum of two interrelated research
projects per Group is required.  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.  However,
applications with first-year budgets in excess of $1,000,000 total
(direct and indirect) should contact the NIAID Scientific
Coordinator, listed under INQUIRIES, for written approval.  Budget
requests should be carefully justified and commensurate with the
complexity of the project.

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.

All policies and requirements that govern the grant program of the
PHS, and the National Institutes of Health (NIH) apply.


The NIAID anticipates making four to eight awards for project periods
up to four years.  The NIAID has set aside $4.2 million total costs
for the first year of funding.  This level of support is dependent on
the receipt of a sufficient number and diversity of applications of
high scientific merit.  Although this program is provided for in the
financial plans of the NIAID, awards pursuant to this RFA are
contingent upon the availability of funds for this purpose.



The NIH and other agencies in the PHS are currently supporting
extramural and intramural projects for the study of the etiology,
natural history, and demographics of AIDS; for the screening of
high-risk individuals; for determining means of diminishing the risk
of infection; and for the development of 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.  Recent surveillance studies
indicate that the total number of AIDS cases in the U.S. reported
through March 1992 was 218,301, with projections by WHO of 30 to 40
million HIV infections worldwide in men, women, and children by the
year 2000.  Moreover, more than 90 percent of these cases will be in
developing countries.  It has been predicted 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 current initiative is to maintain the total NCVDG
network to ten Groups aimed at facilitating and accelerating efforts
in AIDS vaccine development.  A listing of the active NCVDGs can be
found in Appendix I.

Research Goals and Objectives of the NCVDG Program

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

2.  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.
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, and creative methods to enhance
immunogenicity are encouraged.

Approaches may include, but are not limited to:

o  live attenuated vaccines;
o  whole inactivated vaccines;
o  recombinant proteins or protein fragments;
o  novel recombinant viruses or other vectors (e.g., yeast Ty
elements, hepatitis B virus, bacteria);
o  synthetic peptides;
o  combination approaches;
o  DNA immunization.

3.  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, criteria, and staff involvement.

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

5.  For small pilot studies involving a few animals, the Principal
Investigator is expected to have access to a small number of animals
and to primate facilities.  For larger animal studies the applicant
may use NIAID resources such as the SIV Evaluation Units, Chimpanzees
via Interagency Agreement with the National Cancer Institute, and the
Resources and the Reagents Contract.  The Principal Investigator
should contact the program official on how these resources may be


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

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 NIAID strongly prefers that
the Principal Investigator be an employee of the awardee institution.

NIAID SCIENTIFIC COORDINATOR - A scientist of 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.


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

Working Relationships Within a Cooperative Agreement

Under the Cooperative Agreement, a partner relationship exists
between the recipient of the award and 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 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, available under
existing Government contracts.  The interaction of academic and
non-profit research institutions with commercial organizations and
Government is strongly encouraged and is expected to favor
expeditious preclinical development of AIDS vaccines to prevent
transmission of HIV.

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 proposed patent plan among the institutions comprising the Group
must be submitted with the application.  This 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 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. Alan Schultz at the address listed under

Awardee Rights and Responsibilities

The applying Group must define its objectives in accord with its own
interests and perceptions of novel and exploitable approaches and
must develop the detail of the research design following the guidance
given in this RFA.  It is the primary responsibility of the Principal
Investigator to clearly state the objectives of the Group, to perform
the research stipulated in the proposal and to ensure that the
results obtained are published in a timely manner.  The data obtained
will be the property of the awardee.

Specifically, 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.

1.  Meetings

o  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.  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.

o  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 preparing the budget.

o  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

2.  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.

3.  An annual Progress Report should be submitted, which should
include a complete and cumulative list of all  publications
(abstracts, manuscripts, reviews) (co)authored by Group members and
supported in part or in total under this Agreement.

Each Progress Report should also include a brief section outlining
intra-Group interactions that have augmented activities, citing
specific occurrences (e.g., construct X was made under Project 1 and
transferred to Project 2 for analysis).  Inter-Group collaboration
with other NCVDGs should be specified, where applicable. Interaction
with the Scientific Coordinator and the NIAID during the reporting
period should be described.

The Progress Report should routinely include basic information.
Please refer to PHS 2590 noncompeting continuation application form,
which includes the basic information required by NIH for preparation
of the progress report.

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

5.  All published (abstracts, peer reviewed manuscripts, reviews) and
oral presentations of work supported in part or in total by the NCVDG
cooperative agreement must acknowledge the award by including the
mechanism, cooperative agreement number, and Institute, i.e., "This
work was supported in whole (or in part) by the NCVDG program,
cooperative agreement number U01-AI-12345, NIAID.

6.  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.

7.  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.

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.  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,
Dr. Alan M. Schultz, Acting Preclinical Section Chief, may provide
appropriate assistance, advice, and guidance by performing the
following: participating in the design of Group activities; advising
in the selection of sources or resources; 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 the 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

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

o  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.

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

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

o  provision of data from testing conducted in resource contract

o  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.

o  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).

o  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.

o  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

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 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.

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

1.  General Instructions:  Overall Application

For preparing the NCVDG application this Section supplements the
instructions found in form PHS 398 (rev. 9/91), which is available as
an application kit at most grantee institutions and from the Office
of Research Grants Inquiries, Division of Research Grants, National
Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD
20892, telephone 301-496-7441.  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:

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

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

o  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
number and 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

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.

o  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

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.

o  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.

o  Summary Budget Information Required for the Group Application.

Summary budgets should be prepared for the total Group application.

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

2.  Use page 5 from the form PHS 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.

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


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 attached to this RFA.

o  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.  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 laboratory project 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 also is 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

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

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

3.  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.

o  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 U01) 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 Inquiries' publication entitled, "Guidelines for
Establishing and Operating Consortium Grants," January 1989, which
may be obtained by calling 301-496-7441.  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. Jane Unsworth, at

o  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 U01.

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 at the
address listed under INQUIRIES.

Core Units

Since the cores are designated to provide resources for two 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

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 leaders for a NIAID-specified
annual U.S. meeting with  NCVDG Principal Investigators and project
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

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 PHS Form 398 pages should be used:

o  Face Page.  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 PHS 398 Instructions. A
detailed budget is required for the first year (PHS 398, page 4) and
a budget summary for all additional years (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 which 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 398, REV. 9/91 and following the application kit
instructions, except as modified below.

o  Face Page 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 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

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 R0l 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

3.  Research Plan:  Follow the instructions indicated in IV. C.,
pages 19 through 22 of the PHS 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.



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 must be included in the form PHS 398 (rev. 9/91) in
Sections 1-4 of the Research Plan AND summarized in Section 5, Human
Subjects.  Applicants are urged to assess carefully the feasibility
of including the broadest possible representation of minority groups.
However, NIH recognizes that it may not be feasible or appropriate in
all research projects to include representation of the full array of
United States racial/ethnic minority populations (i.e., native
Americans [including American Indians or Alaskan Natives],
Asian/Pacific Islanders, Blacks, Hispanics).

The rationale for studies on single minority population groups should
be provided.

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology,
prevention (and preventive strategies), diagnosis, or treatment of
diseases, disorders or conditions, including but limited to clinical

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

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


Prospective applicants are asked to submit, by February 26, 1993, 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. Alan Schultz at the address
listed under INQUIRIES.


The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these cooperative agreements.  These forms are
available at most institutional offices of sponsored research and may
be obtained from the Office of Grants Inquiries, Division of Research
Grants, National Institutes of Health, 5333 Westbard Avenue, Room
449, Bethesda, MD 20892, telephone 301/496-7441.

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.

Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or principal investigator could be included
with the application.

Submit a signed, typewritten 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, also submit two exact copies of the
application directly to Dr. Dianne Tingley at the address listed

Applications must be received by April 22, 1993.  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.
Therefore, an application cannot be submitted in response to this RFA
that is essentially identical to one that has already been reviewed.
This does not preclude the submission of substantial revisions of
applications already reviewed, but such applications must include an
introduction addressing the previous critique.

This restriction is superseded by an NIH policy permitting concurrent
submission of a duplicate R01 and a component of a multi-project
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


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
non-responsive will be returned to the applicant without review.
Applications with budgets in excess of $1,000,000 total (direct and
indirect) first year costs that 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 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, 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 listed under
Schedule, below.

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:

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

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

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; and the Principal
Investigator's commitment to devote substantial 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 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 percent (time) effort by the Principal
Investigator and each Project Leader should be devoted to the study,
unless there is compelling evidence 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

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, if required, on an interim or permanent basis.

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

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;

o  Likelihood that new strategies and vaccine approaches will be
identified during the course of the proposed study;

o  Plans for effective intra-Group communication and for assuring
cohesiveness within the Group as a whole;

o  Including a mechanism for selecting and replacing key professional
or technical personnel using the framework of the RFA.


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


The opportunity to clarify issues or questions about the RFA from
potential applicants are welcome.  Please send the letter of intent
and direct inquiries regarding the RFA and programmatic issues to:

Alan Schultz, Ph.D.
Acting Chief, Preclinical Section,
Vaccine Research and Development Branch
National Institute of Allergy and Infectious Diseases
Solar Building, Room 2B-01
Bethesda, MD  20892
Telephone:  (301) 496-8200
FAX:  (301) 402-1506

Direct inquiries regarding application preparation and review to:

Dr. Dianne Tingley
Chief, DAIDS Scientific Review Section
Scientific Review Branch
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C-16
Bethesda, MD  20892
Telephone:  (301) 496-0818

Direct inquiries regarding fiscal matters to:

Ms. Jane Unsworth
Chief, AIDS Grants Management Section
Grants Management Branch
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B-22
Bethesda, MD  20892
Telephone:  (301) 496-7075

Applicants who use express mail or courier services are advised to
follow the carrier's requirements for showing a street address.  The
address of the Solar Building is:

6003 Executive Boulevard
Rockville, MD  20852


Letter of Intent Receipt Date:  February 26, 1993
Application Receipt Date:       April 22, 1993
Scientific Review Date:         June 1993
Council Meeting Date:           September 1993
Earliest Award Date:            December 1993


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 Parts 74 and 92.  This
program is not subject to the intergovernmental review requirements
of Executive Order 122372 or Health Systems Agency review.

Appendix I

List of Active NCVDGs

Ronald C. Kennedy, Ph.D.*
Southwest Foundation for Biomedical Research
P.O. Box 28147
(W. Loop 410 at Military Drive)
San Antonio, TX  78284
Telephone:  (512) 674-1410

Richard Allen Young, Ph.D.*
Whitehead Institute for Biomedical Research
Nine Cambridge Center
Cambridge, MA  02142
Telephone:  (617) 258-5218

Murray B. Gardner, M.D.*
Department of Medical Pathology
School of Medicine
University of California
Davis, CA  95616
Telephone:  (916) 752-2710

Lawrence Corey, M.D.*
c/o Virology, D536
Children's Hospital and Medical Center
4800 Sand Point Way, NE
Seattle, WA  98105
Telephone:  (206) 526-2117

Dennis L. Panicali, Ph.D.
Therion Biologics, Inc.
76 Rogers Street
Cambridge, MA  02142
Telephone:  (617) 876-7779

Arsene L. Burny, Ph.D.
Department of Molecular Biology
University of Brussels
67, Rue Des Chevauz
1640 Rhode-St-Genese BELGIUM
Telephone:  32-2-650-9824

Richard W. Compans, Ph.D.
University Alabama at Birmingham
Department of Microbiology
University Station
Birmingham, AL  35294
Telephone:  (205) 934-3049

James Young, Ph.D.
Medimmune, Inc.
35 West Watkins Mill Road
Gaithersburg, MD  20878
Telephone:  (301) 417-0770

Michael A. Murphey-Corb, Ph.D.
Tulane Regional Primate Research Center
Three Rivers Road
Covington, LA  70433
Telephone:  (504) 892-2040, Ext. 275

Flossie Wong-Staal, Ph.D.
Department of Medicine M-023-F
University of California, San Diego
La Jolla, CA   92093
Telephone:  (619) 534-7957

Mark Newman, Ph.D.
Cambridge Biotech Corporation
365 Plantation Street
Worcester, MA  01605
Telephone:  (508) 797-5777

* Award ends in 1993

For Sample Tables listed in Appendix II, please request a copy of
this RFA.


Return to RFAs Index

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