NIH GUIDE, Volume 21, Number 21, June 5, 1992

PA NUMBER:  PA-92-84

P.T. 34


  Infectious Diseases/Agents 

  Viral Studies (Virology) 





National Institute of Allergy and Infectious Diseases


Since the introduction of the measles vaccine in 1963, basic research

on the measles virus has been reduced in this country.  Recently, there

has been a resurgence of measles in the U.S., and measles continues to

be a deadly disease in the developing world.  The National Institute of

Allergy and Infectious Diseases invites investigator-initiated research

grant applications to explore the basic biology of the measles virus

and the host's response to infection.  The purpose is to expand the

understanding of the biologic basis of measles with the goal of

developing improved vaccines to prevent disease and measles-related

infant deaths.  State-of-the-art application of knowledge derived from

this research should lead to new vaccines with reduced primary failure

rates that induce long-lasting immunity and can be given safely to very

young infants.  Success in this endeavor will require basic research in

measles virology, immunity, genetics, and pathogenesis.


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), Research to Better Understand and Prevent Measles,

is related to the priority area of immunization and infectious

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).


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 for the First Independent

Research Support and Transition (FIRST) Award.


Applications considered appropriate responses to this announcement are

the traditional research project grants (R01) and the FIRST Award




From 1981-1988, a steady average of 3,000 cases of measles occurred

each year.  This represents a reduction of over 99 percent from the

400,000 to 700,000 annual cases per year reported before the

introduction of the measles vaccine in 1963.  However, in 1989, there

were 18,193 cases, and in 1990, the number rose to 27,672 cases.  These

cases were reported from all but one state.  The 1990 outbreak year

included the largest number of cases since 1977 and the largest number

of deaths (89) since 1971.  Of the reported cases, 22.7 percent

included complications, and 21.1 percent (5844) required

hospitalization.  At one medical center, nine percent of the

hospitalized cases eventually required intubation.

The epidemiology of the disease in the U.S. is changing, and the

distribution of cases is shifting from older, previously vaccinated,

school-age children to younger, unvaccinated children.  As more

outbreaks occur in younger children, more infants less than 1 year old

are exposed.

The principal cause of the re-emergence of measles in the U.S. is the

failure to vaccinate children at the appropriate age.  Although very

effective when used properly, the current vaccine has deficiencies as

a public health tool.  There is a primary failure rate of about five

percent, and thus, susceptible individuals accumulate in the

population.  The failure rate is higher if the current vaccine is given

at less than 15 months of age when maternal antibody interferes with

vaccine efficacy.  Measles is highly infectious and can spread even in

communities where a high percentage of the population is vaccinated.

In developing countries, measles continues to be a deadly disease

claiming over one and a half million deaths each year.  In those

countries, infants are at greatest risk for serious complications

during the interval between loss of maternal antibody and receipt of

vaccine.  In both U.S. inner cities and inner cities abroad, this

window of exposure is too wide.  In order to close this window and

protect young infants, new vaccines are needed that can safely overcome

the maternal antibody barrier.  Development of improved vaccines will

depend upon new insights gleaned from basic research.

Research Objectives and Experimental Approaches

This program announcement is intended to stimulate measles research on

a broad front, with an emphasis on studies necessary for the

development of improved vaccines.  Research projects are sought that

investigate topics including, but not limited to:  the quantitative and

qualitative differences between vaccine-induced and naturally induced

measles immunity, the antigens required for protective humoral and

cellular immunity, the development of efficient methods for delivery of

immunogens, strategies to overcome maternal antibody as a block to

immunization, characterization of measles immune response in young

infants, the viral correlates of virulence, factors contributing to

immunologically induced adverse events, and the changing epidemiology

of measles.  Also needed are improved laboratory methods for studying

viral genetics and an animal model for measles.





NIH and ADAMHA policy is that applicants for NIH/ADAMHA 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


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.


Applications are to be submitted on the research grant application form

PHS 398 (rev. 9/91) and will be accepted at the standard application

deadlines as indicated in the application kit (February 1, June 1 and

October 1).  Application kits are available at most institutional

business offices 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.  On the first (face) page, item 2a, of the application, the

word "Yes" must be checked and the title and number of the announcement

typed in the space provided:  PA-92-84: Research to Better Understand

and Prevent Measles.

The original and five legible copies of the application must be sent or

delivered to:

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**


Applications in response to this announcement will be assigned on the

basis of established Public Health Service Referral Guidelines.

Applications will be reviewed for scientific and technical merit by

study sections of the Division of Research Grants, NIH, and in

accordance with the standard NIH peer review procedures.   Following

scientific-technical review of the applications considered to have

significant and substantial merit, a secondary review will be by the

appropriate national advisory council or board.


Applications will compete for available funds with all other

applications considered to have significant and substantial merit.  The

following will be considered when making funding decisions:  relative

scientific merit, program relevance, availability of funds.


Direct inquiries regarding programmatic issues to:

James M. Meegan, Ph.D.

Virology Branch

Division of Microbiology and Infectious Diseases

National Institute of Allergy and Infectious Diseases

Solar Building, Room 3A15

Bethesda, MD  20892

Telephone:  (301) 496-7453

Fax:  (301) 402-0804

Direct inquiries regarding fiscal matters to:

Mr. Todd Ball

Chief, Microbiology and Infectious Diseases GM Section

Grants Management Branch

Division of Extramural Affairs

National Institute of Allergy and Infectious Diseases

Solar Building, Room 4B35

Bethesda, MD  20892

Telephone:  (301) 496-7075


This program is described in the Catalog of Federal Domestic Assistance

No. 93.856, Microbiology and Infectious Disease Research.  Grants will

be awarded under the authority of the Public Health Service Act, Title

III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and

administered under PHS grants policies and Federal Regulations 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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