Full Text PA-96-078
 
NOVEL HIV VACCINE DESIGN
 
NIH GUIDE, Volume 25, Number 33, October 4, 1996
 
PA NUMBER:  PA-96-078
 
P.T. 34

Keywords: 
  AIDS 
  Vaccine 

 
National Institute of Allergy and Infectious Diseases
 
PURPOSE
 
The National Institute of Allergy and Infectious Diseases (NIAID)
gives special consideration for funding to scientifically meritorious
applications in response to Program Announcements. Our Program
Announcements identify areas of ongoing research emphasis for the
NIAID. The purpose of this Program Announcement (PA) is to solicit
investigator-initiated research to study novel "high risk - high
impact" HIV vaccine concepts in early stages of development.
 
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 Program
Announcement (PA), "Novel HIV Vaccine Design", is related to the
priority area(s) of immunization and infectious diseases; HIV
infection; sexually transmitted diseases.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-0325 (telephone 202-783-3238).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government. The
total requested project period for an application submitted in
response to this PA may not exceed five years; a foreign application
may not request more than three years of support and will receive no
support for indirect costs.  Domestic applications may include
international components but these components will receive no support
for indirect costs. Racial/ethnic minority individuals, women, and
persons with disabilities are encouraged to apply as Principal
Investigators.  Foreign institutions are not eligible for the First
Independent Research Support and Transition (FIRST) award (R29).
 
MECHANISM OF SUPPORT
 
The mechanisms of support will be the individual research project
grant (R01), Interactive Research Project Grants (IRPG), the First
Independent Research Support Transition (FIRST; R29) award, and the
Small Research Grant (R03).  Research support may also be obtained
through applications for a competitive supplement to ongoing
NIH-funded grants.  Information on the IRPG mechanism is available in
program announcement PA-96-001, published in the NIH Guide, Vol. 24,
No. 35, October 6, 1995.  NIAID uses R03 grants to support small
highly innovative or pilot projects.  Applicants for R03 grants must
follow application guidelines, SMALL RESEARCH GRANTS - NIAID, which
appeared in the NIH Guide, Vol.  25, No. 9, March 22, 1996.  Both of
these publications are available from NIAID program staff listed
under INQUIRIES and on the World Wide Web
(http://www.nih.gov/grants/funding/funding.htm).  Responsibility for
the planning, direction and execution of the proposed project will be
solely that of the applicant.  Applicants are encouraged to
coordinate, through the use of consortium arrangements or
subcontracts, integrated approaches with individuals or institutions
having relevant reagents and expertise in their use, demonstrated
ability in a particular area of relevant research, or access to
relevant animal of patient populations.  Potential applicants are
encouraged to contact the program staff listed under INQUIRIES for
guidance concerning both the organization and scope of the proposed
work and the preparation of the application itself.
 
RESEARCH OBJECTIVES
 
Background
 
The area of HIV vaccine research and development has been, and
continues to be, a major priority for the Division of AIDS NIAID as
outlined in the NIAID HIV/AIDS Research Agenda.  NIAID continues to
be the lead agency within the National Institutes of Health (NIH) for
such efforts.  Vaccines are probably the best tools ever developed
for the prevention of disease, and they are important for both
disease control and control of health care costs.  The National
Cooperative Vaccine Development Groups for AIDS (NCVDG) program is
one of the major NIAID efforts to fund investigator-initiated vaccine
development.  However, vaccine concepts need to be already relatively
well-developed to merit funding of these multi-project awards.  In
contrast, this Program Announcement is designed to encourage and fund
the very earliest steps of vaccine development.
 
Major advances in our understanding of the immune system and its
response to infectious agents have occurred in recent years. These
advances include: characterization of the structure and function of
the T lymphocyte receptor for antigen and the numerous accessory
molecules involved in the initial signal transduction events;
identification and characterization of the numerous cytokines that
regulate immune responses; delineation of the steps involved in
antigen processing and presentation; definition and characterization
of adhesion molecules and their roles in interactions between cells
of the immune system; identification of genes that regulate the
expression and function of many immune system molecules; and, in
several infectious diseases, elucidation of the role (protective vs.
pathogenic) played by different arms of the immune response.  In
addition, advances in the understanding of HIV pathogenesis that may
lead new vaccine strategies have recently been made.  These include
the identification and characterization of HIV coreceptors and the
inhibitory effects of chemokines.
 
Research Objectives and Experimental Approaches
 
Examples of novel experimental approaches to HIV immunization that
would be responsive to this PA would include live virus vectors,
bacterial vector-based vaccines, nucleic acid-based immunogens,
adjuvants, and conformational (nonlinear) synthetic peptide vaccine
strategies.  Vaccination approaches focussing on novel antigen design
or vaccine target antigens are also encouraged.
 
Research objectives responsive to this PA would include
investigations into the mechanisms of protective immunity required
for the development of safe and effective HIV vaccines. Some examples
of relevant research objectives are given below; these examples,
however, are not intended to be all-encompassing or limiting.
 
o  Incorporation of antigen or antigenic peptides into targeting
molecules that will more efficiently deliver them to antigen
presenting cells or specific lymphoid tissues including mucosal
inductive sites
 
o  Manipulation of antigen processing and presentation pathways to
enhance cell-mediated immunity (e.g.,preferential induction of
cytotoxic T lymphocyte (CTL) responses)
 
o  Concomitant administration of appropriate cytokines or
costimulatory molecules with antigens to enhance specific immune
effector functions (e.g., Th1 [type 1] vs. Th2 [type 2] immune
responses and immunoglobulin isotypes) or to enhance mucosal
responses.
 
Vaccine concepts that are already being tested in primate models or
in clinical trials would not be responsive to this PA.
 
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 and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990. The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and printed in
the NIH Guide for Grants and Contracts, Volume 23, Number 11, March
18, 1994.
 
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
 
APPLICATION PROCEDURES
 
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95) and will be accepted on the standard application
deadlines as indicated in the application kit.  Application kits are
available at most institutional offices of sponsored research and may
be obtained from the Grants Information Office, Office 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@odrockm1.od.nih.gov.
 
The title and number of this program announcement must be typed in
Section 2 on the face page of the application.
 
The completed original and five legible, single-sided copies of the
application must be sent or delivered to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817-7710 (for express/courier service)
 
FIRST (R29) applications must include at least three sealed letters
of reference attached to the face page of the original application.
FIRST applications submitted without the required number of reference
letters will be considered incomplete and will be returned without
review.
 
Applicants from institutions that have a Center for AIDS Research
(CFAR) or 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 Center Program Director must be included
in the application material.
 
REVIEW CONSIDERATIONS
 
Applications will be assigned on the basis of established PHS
referral guidelines.  Applications will be reviewed for scientific
and technical merit in accordance with the standard NIH peer review
procedures.  As part of the initial merit review, all applications
will receive a written critique and undergo a process in which only
those applications deemed to have the highest scientific merit,
generally the top half of the applications under review will be
discussed, assigned a priority score, and receive a second level
review by the appropriate national advisory council or board.
 
Review Criteria
 
o  Scientific, technical, or medical significance and originality of
the proposed research;
 
o  Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
 
o  Qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;
 
o  Availability of the facilities and resources necessary to perform
the research;
 
o  Appropriateness of the proposed budget and duration in relation to
the proposed research;
 
o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.
 
The initial review group will also examine the provisions for the
protection of human and animal subjects, the safety of the research
environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other
favorably recommended applications.  The following will be considered
when making funding decisions:
 
o  quality of the proposed project as determined by peer review
o  program balance among research areas of the announcement
o  availability of funds
 
INQUIRIES
 
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic (eligibility and
responsiveness) issues to:
 
Frederick R. Vogel, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 2A28A - MSC-7620
Bethesda, MD  20892-7620
Telephone:  (301) 402-0121
FAX:  (301) 402-3684
Email:  FV1V@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Ms. Lesia Norwood
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B34 - MSC 7610
Bethesda, MD  20892-7610
Telephone:  (301) 496-7075
FAX:  (301) 480-3780
Email:  LN5T@nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is supported under authorization of the Public Health
Service Act, Sec. 301 (c), Public Law 78-410, as amended.  The
Catalogue of Federal Domestic Assistance Citation is 93.856,
Microbiology and Infectious Diseases Research, No. 93.855 -
Immunology, Allergy, and Transplantation Research, or both, as
appropriate).  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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