INNOVATION GRANT PROGRAM FOR APPROACHES IN HIV VACCINE RESEARCH

NIH GUIDE, Volume 26, Number 37, November 7, 1997

PA NUMBER:  PAR-98-007

P.T.

National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  February 10, 1998
Application Receipt Date:  March 10, 1998

PURPOSE

The National Institute of Allergy and Infectious Diseases (NIAID)
gives special consideration for funding to scientifically
meritorious applications in response to program announcements
(PAs).  PAs identify current areas of ongoing research emphasis for
NIAID.

This PA is a continuation of the INNOVATION Grant Program for
Approaches in HIV Vaccine Research implemented by NIAID, National
Institutes of Health (NIH), on the recommendation of the AIDS
Vaccine Research Committee (AVRC). This program aims to encourage
the entrance of novel and innovative vaccine discovery and
development concepts into the research pipeline. As such, the
emphasis of this program is on supporting vaccine research projects
that are particularly innovative, novel, high risk/high impact and
show clear promise in advancing AIDS vaccine design or evaluation.
Applications are especially welcome from young investigators and
those not currently active in the field of AIDS research. The
INNOVATION Grant Program utilizes a grant mechanism which provides
funds to projects of an exploratory nature to generate preliminary
data for further studies. In addition, the program utilizes
streamlined review and award processes to accelerate the rate of
response to these new scientific opportunities.  Two general areas
of investigation are targeted in this iteration of the program: 1)
studies to investigate the structure and immunogenicity of HIV
envelope proteins, and 2) studies to investigate mechanisms that
affect cellular immune responses to HIV or related lentiviruses
during disease progression.

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 PA, Innovation Grant Program for Approaches in HIV
Vaccine Research, is related to the priority areas of HIV
infection, immunization and infectious diseases. Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report: 
Stock No. 017-001-00474-0 or Summary Report: Stock No.
017-001-00473) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-0325 (telephone
202-512-1800).

ELIGIBILITY

Applications may be submitted by domestic and foreign for-profit
and non-profit organizations, both public and private, such as
universities, colleges, hospitals, laboratories, units of state and
local governments, and eligible agencies of the federal government.
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as principal investigators.

MECHANISM OF SUPPORT

Research projects will be supported with the
Exploratory/Developmental Research Grant mechanism (R21).  This
mechanism provides short-duration support for preliminary studies
of a highly speculative nature which are expected to yield, within
this time frame, sufficient information upon which to base a well-
planned and rigorous series of further investigations.  Applicants
may request up to two years of support and up to $150,000 per annum
in direct costs, although with compelling justification exceptions
can be made if specific costly reagents, animals, specimens or
laboratory modifications are needed to perform these studies. 
Program staff may be able to advise prospective applicants
concerning NIAID-sponsored resources that may be available to them. 
Contact the program staff listed under INQUIRIES for further
information. The award is non-renewable; however, the hope is that
grantees under this program will progress through this exploratory
phase further along the research/development pipeline; applicants
may elect to seek continuing support for this research through the
R01 mechanism.

Responsibility for the planning, direction, and execution of the
proposed will be solely that of the applicant.

RESEARCH OBJECTIVES

After examination of the state of the art of HIV vaccine discovery,
the National Institute of Allergy and Infectious Diseases and the
AIDS Vaccine Research Committee seek to broaden the base of
scientific inquiry in two key scientific areas related to HIV
vaccine discovery and development.

1) Studies to investigate the structure and immunogenicity of HIV
envelope proteins.

Examples of areas of interest include, but are not limited to:
Studies to elucidate the structure of the native envelope proteins
as they appear on primary HIV isolates, including, studies to
elucidate the changes in primary isolate envelope protein structure
that take place following binding of envelope with CD4 and second
receptors.

Development and evaluation of HIV immunogens that preserve the
native structure of primary isolate envelope proteins, with
emphasis on soluble protein immunogens, pseudovirions, and whole
inactivated virus particles. This also includes methods to
facilitate targeted expression of native immunogens in vivo.

Development and evaluation of HIV immunogens that mimic the
envelope-specific antigenic structures created by the interaction
of envelope proteins with cellular receptors.

Other studies designed to enhance the immunogenicity of the HIV
envelope proteins with emphasis on induction of neutralizing
antibodies to primary isolates.

2) Studies to investigate mechanisms that affect cellular immune
responses to HIV or related lentiviruses during disease
progression. Areas of interest include, but are not limited to:

studies to evaluate helper T cell responses required for the
development or augmentation of cytolytic T cell responses and the
effect of diminishing helper T cell responses on cytolytic effector
functions during disease progression.

studies to determine the effect of lentiviral replication or
lentiviral protein expression on cellular immune effector
functions.  These can include studies to examine viral effects on
expression of  peptide-MHC complexes and/or co-stimulatory
molecules, and the impact of these effects on cellular immune
recognition.

Studies to evaluate the impact of immune evasion of the virus by
mutation at sites recognized by immune effector cells or antibodies
are not encouraged under this program announcement.

in the vaccinated or acutely infected host,  investigate the
accessibility of infected cells to cellular immune responses in
vivo.  This can include studies to assess the fate of these
effector cells, as well as the functional activity of cellular
immune responses on infected cells in vivo. studies to develop
novel methods for assaying lentivirus-specific T cell effector
functions (i.e., CTL and T cell help). Methods that are rapid,
reproducible and amenable to large-scale application are sought.

To help meet the research objectives defined by NIAID and the AIDS
Vaccine Research Committee, research applications intended to
produce preliminary data or precedent for an idea or a concept are
particularly encouraged.

SPECIAL REQUIREMENTS

Awardees will be expected to attend a meeting convened by NIAID to
showcase the progress of the work funded under this program.
Details of this meeting will be provided post-award. Thus,
applicants should include in their budget request funds for the PI
to attend one meeting in the Washington, DC area.

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 are provided that inclusion is inappropriate with
respect to the health of the subjects of 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", which have been
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.

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

LETTER OF INTENT

As stated above, the Innovation grant program uses accelerated
review and award processes.  To facilitate these processes,
applicants are asked to submit, by February 10, 1998, a letter of
intent that includes a descriptive title of the proposed research,
the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and
participating institutions, and the number and title of this
program announcement.  A letter of intent is not required, is not
binding, and does not enter into the review of a subsequent
application.

The letter of intent is to be sent to:

Dr. Peter R. Jackson
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4C10, MSC 7610
Bethesda, MD  20892-7610
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 496-2550
FAX:  (301) 402-2638
Email:  pj8v@nih.gov

APPLICATION PROCEDURES

Applications are to be submitted on form PHS 398 (rev. 5/95), the
standard application form for research grants.  Application kits
are available at most institutional offices of sponsored research
and may be obtained from the Division of Extramural Outreach and
Information Resources, National Institutes of Health, 6701
Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone
301/710-0267, email: ASKNIH@od.nih.gov. Application kits also may
be obtained electronically via the WWW at
http://www.nih.gov/grants/funding/phs398/phs398.html. Applicants must
adhere to the format and requirements specified in the PHS 398
application kit (rev. 5/95), except as noted below.

For purposes of identification and processing the application, mark
"YES" in item 2 on the face page and enter the PA number PAR-98-
and the title "INNOVATION Grant Program for Approaches in HIV
Vaccine Research".

The research plan will be strictly limited to 10 pages total. 
Appendices may not be used to circumvent the page limitations of
this program announcement.  Applications of that exceed the page
limit will be returned without review.  Investigators are to
indicate in the abstract and in the research plan the area of
investigation the application targets (HIV envelope proteins or
cellular immune responses). A single application may not target
more than one area of investigation. Principal Investigators may
submit only one application per area of investigation. As there are
two areas of investigation targeted, each Principal Investigator
may submit no more than 2 applications. Amended applications will
not be accepted under any circumstances.  Late or incomplete
applications will not be accepted and will be returned.

A modular budget application format will be used, in which budgets
and justifications are simplified. Applicants may apply for up to
two years of support at up to $150,000 per annum, and total direct
costs may be requested in modular increments of  $10,000. The form,
"Detailed Budget for Initial Budget Period" (page 4 of the PHS 398
application kit, rev. 5/95), IS NOT TO BE USED and will NOT be
accepted at the time of application. Applicants are to use the
form, "Budget for Entire Proposed Period of Support" (page 5 of the
PHS 398 application kit, rev. 5/95), leaving blank the categorical
budget table and providing only the requested total direct costs
for each year and total direct costs for the entire proposed period
of support. All project personnel (salaried or unsalaried) should
be listed by name, role on project and percent effort. A narrative
justification is to be provided for each person based on his/her
role on the project and proposed level of effort and biosketches
are to be provided for key personnel. All consultants should be
identified by name and organizational affiliation and the services
they will perform should be described. A narrative justification
should be provided for any major budget item(s), other than
personnel, which would be considered unusual for the scope of
research; otherwise, no specific costs for items or categories
should be shown. Applications exceeding $150,000 in requested total
direct costs also will require a special narrative justification,
identifying the required specific costly reagents, animals,
specimens or laboratory modifications which are required.

The budget justification should begin in the space provided, using
continuation pages as necessary, and should justify the requested
budget on the basis of overall requirements, scientific aims and
scope of the proposed research. If consortium/contractual costs are
requested, the percentage of the subcontract total costs (direct
and indirect) relative to the total direct cost of the overall
project should be specified. The subcontract budget justification
should be prepared according to the instructions provided below.

Note the Special Requirements section of this PA for specific
travel budget information.

All applications must include the completed Checklist (Form Page
II) of the PHS 398 grant application kit (rev. 5/95)

The completed, signed original and three legible, single sided
copies of the application must be sent or delivered to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the same time, two complete copies of the application and all
five copies of any appendices must be sent or delivered to:

Dr. Peter R. Jackson
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4C10, MSC 7610
Bethesda, MD  20892-7610
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 496-2550
FAX:  (301) 402-2638
Email:  pj8v@nih.gov

REVIEW CONSIDERATIONS

Review Procedures

Upon receipt, applications will be reviewed for completeness by the
Center for Scientific Review, NIH, and for responsiveness to the
goals of the PA by NIAID staff. Incomplete applications will be
returned to the applicant without further consideration. 
Applications will be evaluated for scientific and technical merit
by appropriately constituted Scientific Peer Review Group(s) (SPRG)
convened by the NIAID, in accordance with standard NIH review
policies.  There will be two separate reviews: one for each of the
two targeted areas of investigation. As part of the initial merit
review, all applications may undergo a process in which only those
applications deemed to have the highest scientific merit will be
assigned a priority score and receive a second level review by the
National Advisory Council of the National Institutes of Allergy and
Infectious Diseases.

Review Emphasis

The major review emphasis will be placed on the overall concept of
the proposed work and the level of potential impact on moving
toward an AIDS vaccine.

The major goal of the INNOVATION Grant Program is to foster entry
of relatively unexplored vaccine research and design concepts into
the vaccine development pipeline to determine if further study of
the concept is warranted. As such, review of these applications is
not dependent on the submission of comprehensive preliminary data;
however, sufficient data should be presented to justify the
exploratory study.

As noted earlier in this announcement, young investigators and
newcomers to the AIDS field especially are encouraged to apply.
Prior experience in HIV research is not considered a necessary
criterion for evaluating an applicant's abilities or capability of
performing the proposed work.

Review Criteria

The five criteria to be used in the evaluation of these grant
applications are listed below.  To put these criteria in context,
the following information is contained in instructions to the peer
reviewers.

The goals of NIH-supported research are to advance our
understanding of biological systems, improve the control of
disease, and enhance health. The reviewers will comment on the
following aspects of the application in their written critiques in
order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals.  Each of these
criteria will be addressed and considered by the reviewers in
assigning the overall score weighting them as appropriate for each
application.  Note that the application does not need to be strong
in all categories to be judged likely to have a major scientific
impact and thus deserve a high priority score.  For example, an
investigator may propose to carry out important work that by its
nature is not innovative but is essential to move a field forward.

1.  Significance. If successful, will the proposed work advance our
goal of finding an AIDS vaccine? Is it likely the proposed work
will advance the particular scientific area it targets?

2.  Approach. Are the methods, subjects and materials appropriate
to accomplish the goals of the proposed work?

3.  Innovation. Are the proposed aims particularly novel and worthy
of exploratory study?

Does the project employ novel concepts, approaches or method? Does
the project challenge existing paradigms or develop new
methodologies or technologies?

4.  Investigator. Considering their respective backgrounds and
proposed roles, are the proposed personnel qualified to perform the
study?

5.  Environment.  Does the scientific environment in which the work
will be done contribute to the probability of success?  Do the
proposed experiments take advantage of unique features of the
scientific environment or employ useful collaborative arrangements?

The initial review group also will examine: the appropriateness of
proposed project budget; the adequacy of plans to include 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; the provisions for the protection of human
and animal subjects; and the safety of the research environment.

AWARD CRITERIA

Applications will compete for available funds with all other
approved applications assigned to NIAID. The following will be
considered in making funding decisions: the scientific and
technical merit of the proposed project as determined by peer
review, and the availability of funds. In the final selection of
applications to be funded, consideration will be given to achieving
balanced coverage of the scientific areas of emphasis recommended
by NIAID and AVRC.

INQUIRIES

Inquiries are strongly encouraged.  The opportunity to clarify any
issues or questions from potential applicants is welcome.

The Division of AIDS is currently constructing a website for AIDS
vaccine research with an emphasis on facilitating participation in
applying for AIDS vaccine funds. There will be information
describing the various programs targeting AIDS vaccine research and
announcement of currently active AIDS vaccine-related program
announcements, contracts and their associated deadlines. Updates
concerning the continuing Innovation grant program will be
available as well. The site is accessible through the NIAID home.

Applicants new to the field of AIDS research are encouraged to
explore the NIH AIDS Research and Reference Reagent Program and
availability of human specimens at http://www.niaid.nih.gov/reposit/default.htm.
These programs make available small quantities of viruses,
antibodies, HIV proteins, plasmids, and other reagents to researchers.

Direct inquiries regarding programmatic issues to:

Dr. Steve Bende
Division of AIDS
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 2A29, MSC 7620
Bethesda, MD  20892-7620
Rockville, MD 20852 (for express/courier service)
Telephone:  (301) 435-3756
FAX:  (301) 402-3684
Email:  sb22k@nih.gov

Direct inquiries regarding review matters to:

Dr. Peter R. Jackson
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4C10, MSC 7610
Bethesda, MD 20892-7610
Telephone:  (301) 496-2550
FAX:  (301) 402-2638
Email:  pj8v@nih.gov

Direct inquiries regarding fiscal matters to:

Jane Unsworth
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B25, MSC 7610
Bethesda, MD 20892-7610
Telephone:  (301) 402-6824
FAX:  (301) 480-3780
Email:  ju3a@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic
Assistance No. 93.855 and 93.856. Awards are made under
authorization of the Public Health Service Act, Sec. 301(c), Public
Law 78-410, as amended.  Awards will be administered under PHS
grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR
Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems
review.

The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all
tobacco products.  In addition, Public Law 103-227, the Pro-
Children Act of 1994, prohibits smoking in certain facilities (or
in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early
childhood development services are provided to children.  This is
consistent with the PHS mission to protect and advance the physical
and mental health of the American people.

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