MODERN VACCINES FOR MYCOSES

Release Date:  March 6, 1998

PA NUMBER:  PA-98-039

P.T.

National Institute of Allergy and Infectious Diseases

PURPOSE

This program announcement (PA), Modern Vaccines for Mycoses, replaces PA-96-061,
Modern Vaccines for Mycoses and Measles.  Investigator-initiated applications for
measles vaccine research continue to be encouraged although they are no longer
considered responsive this program announcement.

The National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH), invites applications for research on selected
emerging and re-emerging fungal diseases for which new or improved vaccines are
needed.  The goal is to identify and characterize antigens that induce a
protective immune response for the major systemic mycoses of man including, but
not limited to, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis,
cryptococcosis, histoplasmosis, paracoccidioidomycosis, and Pneumocystis
pneumonia.

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, Modern Vaccines for Mycoses, is
related to the priority area(s) 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-
9325 (telephone 202-512-1800).

ELIGIBILITY

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.  Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

Traditional research project grants (R01) may be submitted in response to this
program announcement.  Applications for R01 grants may request up to five years
of support.  Responsibility for the planning, direction, and execution of the
proposed research will be solely that of the applicant.

RESEARCH OBJECTIVES

Background

The purpose of this initiative is to advance the development of new vaccines for
prevention or treatment of the major systemic mycoses of man.  Prior to AIDS, it
was estimated on the basis of skin tests that there were between 25,000 and
100,000 new infections with Coccidioides 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 $45 million for an 18-month period.

The devastating consequences of these diseases, and the less than satisfactory
response to available drugs, suggest that research should explore prevention. A
NIAID workshop (September 1991) on Mycology Research in the 1990s stated that
vaccines should be considered for histoplasmosis, coccidioidomycosis and
cryptococcosis.  Recent NIAID workshops in mycology have reinforced these
concepts. Vaccine approaches for these and selected other fungal diseases are
under exploited.

Not only has work advanced our knowledge of the primary fungal pathogens, but
application of contemporary technology has generated interest in the vaccine
potential for opportunistic fungal pathogens including Candida albicans,
Cryptococcus neoformans, Pneumocystis carinii, and could extend to include
Aspergillus fumigatus.

Long appreciated in the fields of virology and bacteriology, the science of
vaccinology is now being exploited with encouraging results in the fields of
parasitology and oncology.  Mycology should be no exception.

Research Objectives and Scope

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 major systemic fungal pathogens of humans.

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.  These candidates should be evaluated in an 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;
nucleic acid vaccines; or delivery of fungal antigens through viral, bacterial,
or other fungal vectors.

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.

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 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.

For purposes of identification and processing, item 2 on the face page of the
application must be marked "YES".  The PA number and the PA title must also be
typed in section 2.

The completed, signed original and five legible, single-sided copies of the
application must be sent or delivered 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/courier service)

ALL APPLICANTS REQUESTING $500,000 OR MORE IN ANNUAL DIRECT COSTS.  The NIH
Policy Update on Acceptance for Review of Unsolicited Applications that Request
More Than $500,000 Direct Cost for Any One Year applies to applications in
response to this PA.  The Policy Update was published in the NIH Guide for Grants
and Contracts, Volume 25, No. 14, May 3, 1996, and became effective June 1, 1996.

Applicants from institutions that have a General Clinical Research Centers (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 on the basis of established PHS 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.

Applications will be reviewed for scientific and technical merit by study
sections of the Center for Scientific Review, NIH, 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.

Review Criteria

The five criteria to be used in the evaluation of grant applications are listed
below.  To put those 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.  Does this study address an important problem? If the aims of
the application are achieved, how will scientific knowledge be advanced?  What
will be the effect of these studies on the concepts or methods that drive this
field?

2.  Approach.  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

3.  Innovation.  Does the project employ novel concepts, approaches or method? 
Are the aims original and innovative? Does the project challenge existing
paradigms or develop new methodologies or technologies?

4.  Investigator.  Is the investigator appropriately trained and well suited to
carry out this work?  Is the work proposed appropriate to the experience level
of the principal investigator and other researchers (if any)?

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?  Is there evidence of institutional support?

The initial review group will also examine: the appropriateness of proposed
project budget and duration; 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 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.

Dennis M. Dixon, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 3A06, MSC 7630
Bethesda, MD  20892-7630
Telephone:  (301) 496-7728
FAX:  (301) 402-2508
Email:  dd24a@nih.gov

Direct inquiries regarding fiscal matters to:

Todd Ball
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, Room 4B-35
Bethesda, MD  20892-7610
Telephone:  (301) 402-5512
FAX:  (301) 480-3780
Email:  tb22s@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.856.  This program is supported 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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