Full Text PA-96-061
 
MODERN VACCINES FOR MYCOSES AND MEASLES
 
NIH GUIDE, Volume 25, Number 20, June 21, 1996
 
PA NUMBER:  PA-96-061
 
P.T. 34

Keywords: 
  Vaccine 
  Fungal Diseases+ 
  Viral Studies (Virology) 

 
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.  Program
Announcements identify areas of ongoing research emphasis for the
NIAID.
 
The purpose of this PA is to stimulate research on selected emerging
and re-emerging diseases for which new or improved vaccines are
needed.  For the mycoses, the goal is to identify and characterize
antigens that induce a protective immune response for
coccidioidomycosis, histoplasmosis, blastomycosis, and
cryptococcosis.  For measles, the goal is to develop safe, new
measles vaccines that are highly efficacious when administered in
early infancy and that will aid in the control and eventual
eradication of measles.
 
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, Modern Vaccines for Mycoses and Measles, is related to
priority area of immunization-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.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC  20402-0325 (telephone 202-512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities
and 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.
Foreign institutions are not eligible for the First Independent
Research Support and Transition (FIRST) (R29) award.
 
MECHANISM OF SUPPORT
 
Traditional research project grant (R01) ,FIRST award (R29), and
small grant (R03) applications may be submitted in response to this
program announcement.  NIAID uses R03 grants to support small highly
innovative or pilot projects.  Applicants for R03 grants may request
up to $50,000 annual direct costs for a period not to exceed three
years.  Funds and time requested should be appropriate for the
research proposed.  Applicants for R03 grants must follow the special
application guidelines and Terms and Conditions of Award for NIAID
SMALL RESEARCH GRANTS, which appeared in the NIH Guide for Grants and
Contracts, Vol. 25, No. 9, March 22, 1996.
 
RESEARCH OBJECTIVES AND SCOPE
 
Background
 
The purpose of this initiative is to advance the development of new
vaccines in two specific areas:  the mycoses and measles.
 
Prior to AIDS, it was estimated on the basis of skin tests that there
were between 25,000 and 100,000 new infections with C. immitis each
year.  Presently, it is estimated that there are 500,000 new
infections of histoplasmosis each year in the United States.  The
incidence of clinically apparent coccidioidomycosis and
histoplasmosis in HIV+ individuals in highly endemic areas, although
variable, has been found to be as high as 25 percent for each
mycosis. Disease is not limited to immunocompromised hosts. The
recent epidemic of coccidioidomycosis in California resulted in more
than 3,000 cases in 1992 in Kern County alone, with medical costs
estimated at more than $67 million for an 18-month period.
 
A NIAID workshop (September 1991) on Mycology Research in the 1990s
stated that vaccines should be considered for histoplasmosis,
coccidioidomycosis and cryptococcosis, and recent NIAID workshops
have reinforced these concepts. Vaccine approaches for these and
selected other fungal diseases are under exploited.  The devastating
consequences of these diseases, and the less than satisfactory
response to available drugs, suggest that research should explore
prevention.
 
Between 1981 and 1988, a steady average of 3,000 cases of measles
occurred each year.  This rate was a reduction of over 99 percent
from the 400,000 to 700,000 annual cases reported before the
introduction of a vaccine in 1963.  A recent resurgence of measles
has occurred in the United States.  From 1989-1991, 55,165 cases with
123 deaths were reported.
 
The major cause of the re-emergence of measles in the U.S. was the
failure to vaccinate children at the appropriate age rather than
failure of vaccine efficacy.  However, currently licensed vaccines do
have deficiencies as public health tools, particularly in regard to
efficacy in very young infants.  In developing countries, measles
continues to be a deadly disease claiming over one and a half million
lives each year.  In those countries, infants are at greatest risk
for serious disease and complications during the interval between
loss of maternal antibody and receipt of vaccine at 9-12 months of
age.  During the recent re-emergence of measles in the U.S., the
epidemiology of the disease has changed, and the distribution of
cases shifted from older, previously vaccinated, school-age children,
to younger, unvaccinated children often less than 1-year-old.  Thus,
both internationally and domestically, there is a need for an
efficacious vaccine that can be safely administered earlier in
infancy.  Additionally, a need for an improved measles vaccine is
foreseen since proposed future immunization schedules will emphasize
administration at earlier ages in infancy, and will utilize multiple
combinations of vaccines.
 
Unfortunately, measles is a difficult virus to study because there
are no satisfactory animal models.  An RFA issued by NIAID in late
1992 stimulated measles research and resulted in the development of a
number of potentially new measles vaccine candidates and  promising
new animal model systems.   This PA will attempt to stimulate the
preclinical development and comparative evaluation of these potential
new vaccines, and the further establishment and definition of animal
models.
 
Research Objectives and Experimental Approaches
 
Mycoses: Given the advances in molecular biology, it should now be
possible to engineer candidate antifungal vaccines based upon
specific immunoreactive molecules.  Recent evidence derived from
investigators working independently confirm that these approaches are
possible with the medically important fungi.  It is anticipated that
coordinated research supported under this PA will result in the
identification of antigens with immunoprotective effects demonstrable
in animal models for one or more of the endemic mycoses, and/or
cryptococcosis.
 
Relevant projects for the mycoses could address one or more of the
following objectives:
 
o  The identification of fungal antigens that generate a protective
immune response.  Studies could be focused on the isolation and
identification of antigens that can be utilized in vaccine production
to prevent or treat the above mentioned mycoses and their evaluation
in the appropriate model system.
 
o  The modification or presentation of fungal antigens in a manner
that affords maximal immunoprotective effect. Studies could include,
for example, epitope mapping; construction of multiple antigenic
peptides; use of adjuvants or immune enhancers; use of improved
conjugation techniques for enhanced immogenicity.
 
Measles  This program announcement is intended to stimulate
innovative research on measles, with a strong emphasis on studies to
develop improved vaccines that can safely overcome the maternal
antibody barrier and induce long-lasting protective immunity.
Research projects are sought which investigate topics including, but
not limited to, those listed below.
 
Relevant projects for measles will address one or more of the
following issues:
 
o  Determination of which measles antigens are required to safely
elicit long-lasting, protective humoral and cellular immunity in the
developing immune system of the young infant.
 
o  Elucidation of the impact of maternal antibody on infant immune
response, and development of strategies to overcome maternal antibody
as a block to effective immunization in very young infants.
 
o  Development of an animal model of measles virus infection and
disease which parallels human disease, and which could be used to
study the multiple host and viral factors influencing establishment
of protective immunity in the young infant.
 
o  Elucidation of viral and host factors contributing to measles
immunization-induced adverse events.
 
o  Investigation of elements of measles virus pathogenesis, including
virus-induced immune suppression, and viral correlates of virulence
and attenuation.
 
o  Characterization of the quantitative and qualitative differences
between measles vaccine-induced and naturally-induced protective
immunity.
 
o  Pre-clinical development of efficient immunization methods for the
safe delivery of appropriate measles antigens required for the
establishment of protective immunity.
 
INCLUSIONS OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 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
 
APPLICANTS FOR SMALL RESEARCH (R03) GRANTS ARE TO FOLLOW THE
APPLICATION GUIDELINES IN THE "NIAID SMALL RESEARCH GRANTS" NOTICE
WHICH APPEARED IN THE NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 25,
No. 9, March 22, 1996 and are available from program staff listed
under INQUIRIES.
 
Applicants are strongly encouraged to call NIAID program staff with
any questions regarding the responsiveness of their proposed project
to the goals of this PA.  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 Office of Extramural
Outreach and Information, National Institutes of Health, 6701
Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301)
710-0267, email: asknih@odrockm1.od.nih.gov.
 
Each application must be identified by checking "YES" on line 2 of
the PHS face page, and the number and title of this program
announcement must be typed in section 2a.
 
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 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
 
APPLICANTS FOR SMALL RESEARCH (R03) GRANTS ARE TO FOLLOW THE
APPLICATION GUIDELINES IN THE "NIAID SMALL RESEARCH GRANTS" NOTICE
WHICH APPEARED IN THE NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 25,
No. 9, March 22, 1996 and are available from program staff listed
under INQUIRIES.
 
Applications will be assigned on the basis of established PHS
referral guidelines.  Program staff will be responsible for
determining whether an application is responsive to the goals of the
PA.  Applications will be reviewed for scientific and technical merit
by study sections of the Division of Research Grants, NIH, in
accordance with the standard NIH peer review procedures.  Following
scientific/technical review, the applications will receive secondary
review by the appropriate national advisory council.
 
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.
 
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 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 and 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:  quality of the proposed project as
determined by peer review, program balance among research areas of
the announcement, and 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 mycoses programmatic (eligibility and
responsiveness) issues to:
 
Dennis M. Dixon, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Solar Building, Room 3A-06
6003 Executive Boulevard - MSC 7630
Bethesda, MD  20892-7630
Telephone:  (301) 496-7728
FAX:  (301) 402-0508
Email:  dd24a@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Louise Kreh
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4B-27
6003 Executive Boulevard MSC 7610
Bethesda, MD  20892-7610
Telephone:  (301) 496-7075
FAX:  (301) 480-3780
Email:  lk5k@nih.gov
 
Direct inquiries regarding review issues and special instructions for
application preparation and mail two copies of the R03 application
and all five sets of any appendices to:
 
Stanley Oaks, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Solar Building, Room 4C06
6003 Executive Boulevard - MSC 7610
Bethesda, MD  20892-7610
Telephone:  (301) 496-7042
FAX:  (301) 402-7042
Email: sol4s@nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.856, Microbiology and infectious Disease Research.
Awards are made under authorization 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 52 and 45 CFR Part 74.  This program is
not subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency 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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