INTEGRATED PRECLINICAL/CLINICAL AIDS VACCINE DEVELOPMENT PROGRAM
Release Date: March 6, 2000
PA NUMBER: PAR-00-072
National Institute of Allergy and Infectious Diseases
Application Receipt Dates: June 13, 2000, 2001, 2002.
APPLICATIONS IN RESPONSE TO THIS PROGRAM ANNOUNCEMENT (PA) MUST BE PREPARED
USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS FOR
COMPLETING THE APPLICATION ARE IN THE NIAID BROCHURE ENTITLED "INSTRUCTIONS
FOR APPLICATIONS FOR MULTI-PROJECT AWARDS.
PURPOSE
The National Institute of Allergy and Infectious Diseases (NIAID) of the
National Institutes of Health (NIH) invites applications for research aimed
at obtaining a safe and efficacious vaccine against HIV or AIDS. NIAID
supports the progressive stages of AIDS vaccine research and development
including basic research, iterative product development, and clinical trials.
NIAID supports AIDS prophylactic vaccine research and development via three
grant programs. The Innovation Grant Program for AIDS Vaccine Research
supports high risk/high impact early stage concept evaluation for projects
with limited preliminary data. The HIV Vaccine Research and Design (HIVRAD)
Program supports multi-project investigator-initiated HIV vaccine design and
development research. The Integrated Preclinical/Clinical AIDS Vaccine
Development (IPCAVD) Program supports iterative product development and
optimization in the later stages of vaccine research and includes limited
human studies.
This Program Announcement (PA) replaces PAR-97-056 and is a continuation of
the Integrated Preclinical/Clinical AIDS Vaccine Development Program. For an
overview of these research programs and other information, visit the NIAID
AIDS Vaccine Research Website at:
http://www.niaid.nih.gov/daids/vaccine/default.htm
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas. This PA, INTEGRATED
PRECLINICAL/CLINICAL AIDS VACCINE DEVELOPMENT PROGRAM , is related to the
focus area(s) of immunization and infectious diseases, HIV infection, and
sexually transmitted diseases. Potential applicants may obtain a copy of
"Healthy People 2010" at http://www.health.gov/healthypeople
ELIGIBILITY
Applications may be submitted by domestic for-profit and non-profit
organizations, public and private, such as universities, colleges, hospitals,
laboratories, units of State and local governments, and eligible agencies of
the Federal government. In accordance with NIH policy, foreign institutions
are not eligible for Program Project Grant (P01) awards. However, for this
initiative, NIAID has been granted an exception. Foreign institutions may
apply for grants under this Program Announcement however all other
restrictions on foreign grant applications will apply. Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to apply as
Principal Investigators.
MECHANISMS OF SUPPORT
Program project grant (P01) applications may be submitted in response to this
announcement. Program project grants support broadly based,
multidisciplinary research programs that have a well-defined, central
research focus or objective. An important feature is that the
interrelationships of the individual scientifically meritorious projects will
result in a greater contribution to the overall program goals than if each
project were pursued individually. Standard NIH policy requires P01
applications to consist of a minimum of three interrelated individual
research projects that contribute to the program objective. This type of
award also can provide support for certain common resources termed cores.
Such resources should be utilized by two or more projects within the award.
An exception to standard policy has been granted for this program
announcement such that fundable applications must have at least two (2)
projects and one core. The total project period for P01 grants may not exceed
five years.
Responsibility for the planning, direction, and execution of the proposed
research will be solely that of the applicant.
Applicants for P01 grants must follow special application guidelines in the
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS (April 1999); this brochure is available via the WWW at:
http://www.niaid.nih.gov/ncn/grants/multibron.htm
In the case of any discrepancies, this PA will supercede the instructions in
the Brochure.
RESEARCH OBJECTIVES
Background
Vaccine research requires contributions from multiple fields including
immunology, virology, animal models, and molecular biology. The IPCAVD
program aims to foster the later stages of AIDS vaccine development that
includes the transition of promising concepts from laboratory to clinic.
Research Objectives and Scope
As stated above, the overall goal of this PA is to support multidisciplinary
research that will lead to a safe and protective AIDS vaccine. As such,
IPCAVD applications must include human clinical studies within the term of
the award.
Studies responsive to this PA can include, but are not limited to: vaccine
delivery and vector systems; methods of enhancing specific immune responses;
dissection of viral and host contributions to immunity and combinations of
these. Research directed toward optimization of existing vaccine concepts is
also encouraged.
Applications can include preclinical research, vaccine production, and
clinical testing. However, preclinical research alone, without clear,
feasible, and realistic plans for progressing to human testing within the
period of award, will not be considered responsive to this PA. Applicants
must delineate discrete goals, milestones, and criteria that can be used to
evaluate progress toward a testable vaccine. If preclinical evaluation of
the concept, according to these milestones, demonstrates that further studies
should not be pursued, funding for those latter phases of the project will
not be released.
Applicants may also request funds for production of clinical grade
(manufactured under Food and Drug Administration (FDA)-Good Laboratory
Practices (GLP) guidelines) vaccine and subsequent in vivo testing.
Applicants seeking to move from preclinical research to lot production must
detail the goals, milestones, and criteria, which will be reviewed by the
Scientific Review Group (SRG), to justify the release of funds for this
purpose.
Since human studies will require the filing of an IND application with the
FDA, certain regulatory requirements must be met prior to the release of
funds to initiate this part of the study. Additionally, information that may
be useful in improving or refining the vaccine may arise during these
clinical studies. The applicant should address how the results of the
clinical evaluations will be used to either improve the vaccine concept or
advance it through further human testing.
Applicants must address the following issues in their application regarding
human studies: design of the clinical trial, plans for recruitment,
enrollment, education and follow-up of clinical subjects, including attention
to the possibility of social harms and discrimination arising from vaccine-
induced positive screening tests that may be interpreted incorrectly as HIV
infection, plus documentation of compliance with all applicable federal
(FDA), state and local laws and regulations governing clinical research. The
completeness and feasibility of these plans will be reviewed by the SRG.
Investigators are encouraged to discuss clinical evaluation of their
candidate vaccines by the NIAID-supported HIV Vaccine Trials Network (HVTN)
with NIAID Program Staff. For clinical trials, NIAID Program Staff can
arrange for review of data by the AIDS Vaccine Data and Safety Monitoring
Board, which reviews data for HVTN trials. Funds available under this PA are
for small-scale early phase clinical studies. Investigators interested in
pursuing NIAID support for large-scale human vaccine trials should contact
the HVTN (see below for contact information).
Vaccine research focused solely on therapeutic application is not responsive
to this announcement. The safety evaluation of immunogens in infected animals
or people may be included if these studies directly support the development
of a prophylactic vaccine. For information on programs that support
therapeutic vaccine development please contact program staff.
The participation of the private sector is strongly encouraged because of its
unique infrastructure, experience in product manufacture and development, and
capital resources. These capabilities are considered to be especially
appropriate and valuable for collaborative studies in this area. For
example, a pharmaceutical or biotechnology company might participate in an
individual project that provides testing of a preclinical concept and
sufficient production of a vaccine when the product is needed to conduct
studies.
SPECIAL REQUIREMENTS
All awardees are strongly encouraged to attend an NIAID-sponsored annual
meeting on AIDS vaccine research and development and may include a request
for travel funds for this purpose.
Patent Coverage
Since applications may involve several institutions, including the private
sector, complex patent situations may arise. To avoid delays in the
implementation of new vaccines for HIV related to intellectual property
issues, each multi-project group is to provide a plan as part of the
application, detailing 1) the approach, agreed to by all parties, to be used
for obtaining patent coverage and for licensing, where appropriate, and, 2)
the procedures to be followed for the resolution of legal problems that
potentially may develop.
Attention is drawn to the reporting requirements of 35 U.S.C. Parts 200-212
and 37 CFR Part 401 or FAR 55.227-11. Instructions were also published in the
NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 19, No. 23, June 22, 1990. Note that
non-profit organizations (including universities) and small business firms
retain the rights to any patent resulting from Government grants or
cooperative agreements.
It is also noted that 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 there from. 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
the Group's particular circumstances.
The agreement among the institutions comprising the Group, signed and dated
by the organizational officials authorized to enter into patent arrangements
for each Group member and member institution, must be delivered prior to
submission of the application to Dr. Steve Bende, at the address listed under
INQUIRIES. A copy of the patent agreement should also be submitted with the
application. If the Group wishes to place all inventions and discoveries
resulting from these studies within the public domain, a letter to that
effect must be submitted to Dr. Bende in lieu of the patent agreement. The
letter must be co-signed by the Principal Investigator, each of the Project
Leaders, and each of the business officials representing the respective
institutions.
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 the Extramural Invention Reports Office at 301 435 1986.
Terms of Award
On February 24, 2000, NIAID announced its expanded policies on MONITORING OF
CLINICAL TRIALS AND STUDIES in the NIH Guide at:
http://grants.nih.gov/grants/guide/notice-files/NOT-AI-00-003.html.
Applications and awards with component clinical trials and studies must
adhere to these policies including the terms and conditions of award; see
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf
Phased Release of Funds:
For awards including vaccine pilot lot production, release of funds for this
purpose will be contingent on successful accomplishment of milestones and
criteria proposed by the applicant. Release of funds for clinical research
will be contingent on successful accomplishment of milestones and criteria
for preclinical evaluation of the product and plans for its production and
availability of funds.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups and
their sub-populations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear,
compelling rationale, and justification are provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).
All investigators proposing research involving human subjects should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research", published in the Federal Register of March 28, 1994 (FR 59 14508-
14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18,
1994 which is available at:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research, conducted or supported by
the NIH, unless there are scientific and ethical reasons not to include them.
This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and which is available at the following
URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators may obtain copies from these sources or from Dr. Steve Bende
(listed in INQUIRIES below) who may also provide additional relevant
information concerning the policy.
APPLICATION PROCEDURES
Applicants for P01 grants must follow special application guidelines in the
NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS (April 1999); this brochure is available at:
http://www.niaid.nih.gov/ncn/grants/multibron.htm
Where differences exist, instructions in this Program Announcement take
precedence over instructions in the Multi-Project Awards Brochure, which
takes precedence over the standard PHS 398 instructions.
The research grant application form PHS 398 (rev. 4/98) is to be used in
applying for these grants. Application kits are available at most
institutional offices of sponsored research and from the Division of
Extramural Outreach and Information Resources, National Institutes of Health,
6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-
0714, email: Grantsinfo@nih.gov Applications are also available at:
http://grants.nih.gov/grants/forms.htm.
All applications in response to this PA must include detailed rather than
modular budgets.
For purposes of identification and processing, item 2a on the face page of
the application must be marked "YES" and the PA number as stated on the title
page of this Program Announcement and the words "INTEGRATED
PRECLINICAL/CLINICAL AIDS VACCINE DEVELOPMENT PROGRAM" must be typed in.
Applications must be received by June 13 of the 3 years of the PA.
Applications that are not received as a single package on the receipt date or
that do not conform to the instructions contained in PHS 398 (rev. 4/98)
Application Kit (as modified in, and superseded by, the NIAID BROCHURE
ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS"), will be
judged non-responsive and will be returned to the applicant.
It is required that the appropriate NIAID program contact be consulted before
submitting the application to obtain approval for acceptance of applications
requesting direct costs $500,000 or more in any year of the proposed grant.
(See program contact under INQUIRIES).
Submit a signed, typewritten original of the application, including the
checklist; the original of the appendices (if any); and three signed, exact,
single-sided photocopies of the application (no copies of the appendices), in
one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040 - MSC 7710
Bethesda, MD 20892-7710
Bethesda, MD 20817 (for express mail or courier service)
At the time of submission, two additional exact copies of the grant
application and all five copies of any appendix materials must be sent to Dr.
Dianne Tingley at the address listed under INQUIRIES.
Concurrent submission of an R01 and a Component Project of a Multi-project
Application: Current NIH policy permits a component research project of a
multi-project grant application to be concurrently submitted as a traditional
individual research project (R01) application. If, following review, both
the multi-project application and the R01 application are found to be in the
fundable range, the investigator must relinquish the R01 and will not have
the option to withdraw from the multi-project grant. This is an NIH policy
intended to preserve the scientific integrity of a multi-project grant, which
may be seriously compromised if a strong component project(s) is removed from
the program. Investigators wishing to participate in a multi-project grant
must be aware of this policy before making a commitment to the Principal
Investigator and awarding institution.
GCRC INSTITUTIONS
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 Center as a resource for conducting the proposed research. If
so, a letter of agreement from the GCRC Program Director must be included in
the application material.
REVIEW CONSIDERATIONS
Review Procedures
Applications will be assigned to NIAID on the basis of established NIH
referral guidelines. Upon receipt, applications will be reviewed for
completeness by the NIH Center for Scientific Review. Incomplete
applications will be returned to the applicant without further consideration.
P01 applications that are complete and responsive to this PA will be
evaluated for scientific and technical merit by an appropriate peer review
group convened by the NIAID.
Review Criteria
The NIAID brochure "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT
AWARDS (April 1999) states the general review criteria for P01 applications.
Additional review criteria specific to this PA are:
For preclinical evaluation of vaccine concepts/strategies reviewers will
consider:
A. The overall scientific and technical merit of the proposed vaccine study
with regard to impact on the AIDS epidemic.
B. Appropriateness and adequacy of the experimental approach and the
methodology proposed to carry out the research, specifically including the
feasibility of the applicant's plans, and the availability of necessary
facilities to conduct the research. In addition, the goals and milestones to
be met for progression through to production and in vivo trial will be
reviewed for adequacy, feasibility, and likelihood of attainment during the
period of the grant.
For production of clinical grade vaccine product, reviewers will consider:
A. Appropriateness of the scientific rationale for advancing to the vaccine
production stage, and suitability of the proposed milestones and criteria to
be attained in order to merit funding. The SRG will judge the suitability of
such criteria. If satisfactory proof that these criteria and milestones have
already been met is supplied, funds to produce vaccine product will be
released at the time of grant award.
B. Completeness and feasibility of the plan to produce the vaccine. This
includes adherence to any and all federal (FDA), state, and local regulations
for the production of clinical grade material.
For clinical studies, reviewers will consider:
A. Scientific, technical, and clinical significance and originality of the
proposed research.
B. The completeness of plans for the design of the clinical trial, plans for
recruitment, enrollment, education and follow-up of clinical subjects. This
includes the safety, monitoring, and possibility of social harms and
discrimination arising from vaccine-induced positive screening tests that may
be interpreted incorrectly as HIV infection, and other harms such as true HIV
infection as the result of vaccination, and compliance with all applicable
Federal, State and local laws and regulations governing clinical research
will be reviewed by the SRG. Appropriateness of the proposed criteria and
milestones to be met to permit release of funds and progression of the study
to the clinical phase.
For all applications:
A. Leadership and research experience of the Principal Investigator and key
staff in the areas of proposed research. For clinical-grade vaccine
production, the track record and facilities of the proposed producer. For
clinical trials research, the leadership, scientific ability and
administrative competence of the applicant for the development,
implementation and management of pilot clinical trials, and for effective
interaction with designated NIAID staff.
B. Adequacy of the proposed means for protecting against adverse effects of
the research upon humans, animals or the environment, where such are
involved.
C. Justification of the usefulness of the core facilities to the various
research projects, including the administrative core, if applicable. Each
core unit must provide essential facilities or service for two or more
approved individual projects.
D. 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.
The initial review group will also examine: the adequacy of plans to include
children and both genders and minorities and their subgroups as appropriate
for the scientific goals of the research and plans for the recruitment and
retention of subjects.
AWARD CRITERIA
Applications will compete for available funds with all other favorably
recommended applications. The following will be considered when making
funding decisions: quality of the proposed project as determined by peer
review, program balance among research areas of the announcement, and
availability of funds. The NIAID gives special consideration for funding,
including award of grants beyond the established NIAID percentile and
priority score paylines, to scientifically meritorious applications in
response to Program Announcements.
INQUIRIES
Written and telephone inquiries are encouraged. The opportunity to clarify
any issues or questions from potential applicants is welcome.
Requests for the NIAID brochure INSTRUCTIONS FOR APPLICATIONS FOR MULTI-
PROJECT AWARDS as well as inquiries regarding programmatic (research scope,
eligibility and responsiveness) issues may be directed to:
Steve Bende, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Rm. 4107, MSC 7628
Bethesda, MD 20892-7628
Telephone: (301) 435-3756
Fax: (301) 435-6511
Email: sb22k@nih.gov
Direct inquiries regarding review issues to:
Dr. Dianne Tingley
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Dr. Room 2148, MSC 7616
Bethesda, MD 20892-7616
Bethesda, MD 20817 (for express/courier service)
Telephone: (301) 496-0818
FAX: (301) 402-2638
Email: dt15g@nih.gov
Direct inquiries regarding fiscal matters to:
Jane Unsworth
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Rm. 2128, MSC 7614
Bethesda, MD 20892-7614
Telephone: (301) 402-6824
Fax: (301) 480-3780
Email: ju3a@nih.gov
Direct inquiries regarding the HVTN to:
Dr. Jorge Flores
Division of AIDS
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Rm. 4154, MSC 7628
Bethesda, MD 20892-7628 (301)
Telephone: (301) 435-3758
Fax: (301) 435-6511
Email: jf30t@nih.gov
AUTHORITY AND REGULATIONS
This program is supported under authorization of the Public Health Service
Act, Sec. 301 (c) and 405 (42 USC 241 and 284). The Catalogue of Federal
Domestic Assistance Citations are Sec. 93.856, Microbiology and Infectious
Diseases Research, and No. 93.855 - Immunology, Allergy, and Transplantation
Research. Awards will be administered under PHS grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74 and 94. This program is not
subject to the intergovernmental review requirements of Executive Order 12372
or Health Systems review.
The Public Health Service strongly encourages all grant and contract
recipients to provide a smoke-free workplace and promote the non-use of all
tobacco products. In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or, in some cases, any portion
of a facility) in which regular or routine education, library, day care,
health care or early childhood development services are provided to children.
This is consistent with the PHS mission to protect and advance the physical
and mental health of the American people.
Weekly TOC for this Announcement
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