MUCOSAL IMMUNITY IN THE UROGENITAL TRACT

NIH GUIDE, Volume 22, Number 1, January 8, 1993



PA NUMBER:  PA-93-034



P.T. 34



Keywords:

  Urogenital System 

  Immunology 



National Institute of Allergy and Infectious Diseases

National Institute on Aging

National Institute of Child Health and Human Development

National Institute of Diabetes and Digestive and Kidney Diseases



The Division of Allergy, Immunology and Transplantation (DAIT) and

the Division of Microbiology and Infectious Diseases (DMID) of the

National Institutes of Allergy and Infectious Diseases (NIAID); the

National Institute on Aging (NIA); the National Institute of Child

Health and Human Development (NICHD); and the National Institute of

Diabetes and Digestive and Kidney Diseases (NIDDK) invite research

project grant applications for support of basic and preclinical

studies aimed at elucidating the normal and pathologic cellular and

humoral immune responses in the urogenital tract.



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), Mucosal Immunity in the Urogenital Tract, is

related to the priority area of sexually transmitted diseases,

maternal and infant health, immunization and infectious diseases, and

diabetes and chronic disabling diseases.  Potential applicants may

obtain a copy of "Healthy People 2000" (Full Report:  Stock No.

017-001-00474-0) or "Healthy  People 2000" (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



Research grant 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.

Applications from minority individuals and women are encouraged.

Foreign institutions are not eligible to apply for the First

Investigator Research Support and Transition (FIRST) (R29) award.



MECHANISM OF SUPPORT



The mechanism of support will be the individual research project

grant (R01) and the FIRST (R29) award.  Multidisciplinary approaches

that involve collaborative efforts among investigators in the fields

of basic immunology, endocrinology, urology and gynecology are

strongly encouraged.



Policies that govern research grant programs of the National

Institutes of

Health (NIH) will prevail.



RESEARCH OBJECTIVES



Background



Although considerable progress has been made in understanding the

immune responses in mucosal surfaces of the airways and the digestive

tract, there is a serious lack of information regarding the immune

responses in the mucosal lining of the urogenital system.  Recent

technologic advances should make it possible to isolate and

characterize both the cells and the molecules that participate in the

maintenance of immune homeostasis in the genitourinary tract.



Millions of women and men of all ages suffer urinary and genital

infections that not only cause pain, but could also have unwanted

effects on fertility and urinary function.  Despite control efforts

to prevent the spread of STDs, including human immunodeficiency virus

(HIV) infection, both bacterial and viral STDs remain epidemic in

many areas of the United States.  Although curative therapy is

available for some of these acute infections, many individuals go on

to develop serious complications and chronic disease.  Furthermore,

sexually transmitted infections have also been implicated in

increased risk of HIV transmission.



Unfortunately, except for Hepatitis B, there are no vaccines for

STDs.  STD vaccine development is extremely difficult and complex for

reasons related primarily to (1) the nature of the host-pathogen

relationship and (2) the consequences of co-infection with more than

one sexually transmitted pathogen.  As obligate pathogens of humans,

the etiologic agents of these diseases have evolved to effectively

avoid, subvert, or ignore the immunodominant host response.

Furthermore, the presence of multiple infections in the reproductive

tract is likely to complicate vaccine development as pre-existing

STDs compromise epithelial barriers through tissue fragility,

induction of inflammatory cytokines and the recruitment of target

cells, such as lymphocytes (in the case of HIV), thereby lowering the

infectious dose and compromising vaccine efficacy.



Detailed knowledge of the basic mechanisms that normally participate

in mucosal resistance against these conditions could create new

opportunities for vaccine development and intervention.



Research Objectives and Scope



Areas of interest include:



o  Phenotypic and functional analysis of normal immune cell

components in the urogenital mucosal linings, and changes during

puberty, menopause and post-menopause.



o  Studies on the effects of steroid hormones on the composition and

function of immune cells normally present in the mucosa of the

urogenital tract.



o  Determination of the cellular and molecular factors that induce

and regulate antibody production by mucosal-associated lymphocytes.



o  Effects of different forms of antigen presentation and adjuvants

on the development of local immunity.



o  Mechanisms mediating the relationship between immune responses

developing in the urogenital mucosa and systemic immunity.



o  Identification of critical factors that lead to development of

full or partial protective immunity in the mucosal surfaces of the

urogenital tract.



o  Identification of the kinetic parameters of protective immune

responses and of new means to enhance and prolong protective

immunity.



o  Determination of the molecular basis for the observed differences

between the immune responses of the male and female reproductive

tract and of the influence of reproductive hormones on infectivity

and the host response to infection.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH

POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are required to include minorities and women

in study populations so that research findings can be of benefit to

all persons at risk of the disease, disorder or condition under

study; special emphasis must be placed on the need for inclusion of

minorities and women in studies of diseases, disorders and conditions

that disproportionately affect them.  This policy is intended to

apply to males and females of all ages.  If women or minorities are

excluded or inadequately represented in clinical research,

particularly in proposed population-based studies, a clear compelling

rationale must be provided.



The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of

the study.  This information must be included in the form PHS 398 in

Sections 1-4 of the Research Plan AND summarized in Section 5, Human

Subjects.  Applicants are urged to assess carefully the feasibility

of including the broadest possible representation of minority groups.

However, NIH recognizes that it may not be feasible or appropriate in

all research projects to include representation of the full array of

United States racial/ethnic minority populations (i.e., Native

Americans (including American Indians or Alaskan Natives),

Asian/Pacific Islanders, Blacks, Hispanics).  The rationale for

studies on single minority population groups must be provided.



For the purpose of this policy, clinical research is defined as human

biomedical and behavioral studies of etiology, epidemiology,

prevention (and preventive strategies), diagnosis, or treatment of

diseases, disorders or conditions, including but not limited to

clinical trials.



The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.



For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including

minorities.



If the required information is not contained within the application,

the review will be deferred until the information is provided.  Peer

reviewers will address specifically whether the research plan in the

application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the

selected study population is inadequate, it will be considered a

scientific weakness or deficiency in the study design and will be

reflected in assigning the priority score to the application.



All applications for clinical research submitted to NIH are required

to address these policies.  NIH funding components will not award

grants or cooperative agreements that do not comply with these

policies.



APPLICATION PROCEDURES



Applicants are to use the research grant application form PHS 398

(rev. 9/91).  For purposes of identification and processing, check

yes on item 2a of the face page and enter the title, PA-93-: Mucusal

Immunity in the Genital Tract.  Applications will be accepted in

accordance with the standard submission dates for new applications:

February 1, June 1, and October 1.  All applications will be assigned

by the Division of Research Grants (DRG) for review according to the

NIH process for regular research grant applications.



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 GCRC as a resource for conducting

the proposed research.  If so, a letter of agreement from either the

GCRC program director or principal investigator could be included

with the application.



Application kits are available at most institutional offices of

sponsored research and may be obtained from the Office of Grants

Inquiries, Division of Research Grants, National Institutes of

Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone

(301) 496-7441.



The completed original application and five legible copies must be

sent or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW CONSIDERATIONS



Applications will be assigned on the basis of established PHS

referral guidelines.  Applications will be reviewed for scientific

and technical merit by study sections of the DRG, in accordance with

the standard NIH peer review procedures.  Following

scientific-technical review, the applications will receive a

second-level review by an appropriate national advisory council or

board.



AWARD CRITERIA



Applications will compete for available funds with all other approved

applications.  The following will be considered in making funding

decisions:  quality of the proposed project as determined by peer

review, availability of funds, and program balance among research

areas of the announcement.



INQUIRIES



Requests for additional information and questions regarding this

program may be directed to:



Dr. Susana Serrate-Sztein

Division of Allergy, Immunology and Transplantation

National Institute of Allergy and Infectious Diseases

Solar Building, Room 4A20

Bethesda, MD  20892

Telephone:  (301) 496-7985

FAX:  (301) 402-0175



Dr. Penny Hitchcock

Sexually Transmitted Diseases Branch

Division of Microbiology and Infectious Diseases

National Institute of Allergy and Infectious Diseases

Solar Building, Room 3A21

Bethesda, MD  20892

Telephone:  (301) 402-0443

FAX:  (301) 402-1456



Dr. David H. Lavrin

Biology of Aging Program

National Institute on Aging

Gateway Building, Room 2C231

Bethesda, MD  20892

Telephone:  (301) 496-6402



Dr. Michael E. McClure

Reproductive Science Branch, Center for Population Research

National Institute of Child Health and Human Development

Executive Plaza North, Room 603

Bethesda, MD  20892

Telephone:  (301) 496-6515

FAX:  (301) 496-0962



Dr. Leroy M. Nyberg

Division of Kidney, Urologic and Hematologic Disorders

National Institute of Diabetes and Digestive and Kidney Diseases

Westwood Building, Room 3A-05A

Bethesda, MD  20892

Telephone:  (301) 496-8248



Direct inquiries regarding fiscal matters to:



Mr. Jeffrey Carow

Chief, Immunology Grants Management Section

Division of Extramural Affiars

National Institute of Allergy and Infectious Diseases

Solar Building, Room 4B29

Bethesda, MD  20892

Telephone:  (301) 496-7075



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal

DomesticAssistance, No. 93.855 - Immunology, Allergic and Immunologic

Diseases Research.  Grants are awarded under the authority of the

Public Health Service Act, Section 301 (42 USC 241) and administered

under PHS grants policies and Federal Regulations, most specifically

at 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 Agency review



.

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