PREPAREDNESS AGAINST ILLEGITIMATE USE OF BACTERIAL PATHOGENS

Release Date:  October 5, 1999

RFA:  AI-00-004

National Institute of Allergy and Infectious Diseases

Letter of Intent Receipt Date:  December 10, 1999
Application Receipt Date:  January 19, 2000

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" 
CONCEPTS.  IT INCLUDES DETAILED MODIFICATIONS TO STANDARD 
APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING 
APPLICATIONS IN RESPONSE TO THIS RFA.

PURPOSE

The purpose of this Request for Applications (RFA) is to 
support basic research on molecular and genetic aspects of 
pathogenesis of, and host immune/defense responses to, the 
following bacterial pathogens: Bacillus anthracis,Yersinia 
pestis, Francisella tularensis, Coxiella burnetii, or 
Brucella species. It is hoped that research from funded 
projects will be used to devise appropriate defense 
strategies that can be implemented shortly before or soon 
after bioterrorist acts.

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 RFA, PREPAREDNESS AGAINST 
ILLEGITIMATE USE OF BACTERIAL PATHOGENS, is related to the 
priority area of immunization and infectious diseases. 
Potential applicants may obtain a copy of "Healthy People 
2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-
profit and non-profit organizations; public and private 
institutions, 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

Specific application instructions have been modified to 
reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining 
efforts being examined by the NIH. Complete and  detailed 
instructions and information on Modular Grant applications 
can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm

The mechanisms of support will be the individual research 
project grant (R01) and the Small (Pilot) Research Project 
Grant (R03). The total requested project period for an 
application submitted in response to this RFA should not 
exceed four years for an R01 or three years for an R03.  

Responsibility for the planning, direction, and execution of 
the proposed project will be solely that of the applicant.

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 
(3) years.  Funds and time requested should be appropriate 
for the research proposed.  

This RFA is a one-time solicitation.  Future competing 
renewal applications will compete with all investigator-
initiated applications and will be reviewed according to 
customary referral and review procedures.

FUNDS AVAILABLE

The estimated total funds (direct and facilities and 
administration [F&A] costs) available for the first year of 
support for all awards made under this RFA will be $ 1.0 
million; depending on Fiscal Year budget appropriations, 
this amount may increase. In Fiscal Year 2000, the NIAID 
plans to fund approximately 3-5 awards.  The usual PHS 
policies governing grants administration and management will 
apply.  Although this program is provided for in the 
financial plans of the NIAID, awards pursuant to this RFA 
are contingent upon the availability of funds for this 
purpose and the receipt of a sufficient number of 
applications of high scientific merit.  Funding beyond the 
first and subsequent years of the grant will be contingent 
upon satisfactory progress during the preceding years and 
availability of funds.

RESEARCH OBJECTIVES

Background

In recent years, there has been a significant change in both 
the nature and degree of the threat posed by the use of 
weapons of biological warfare. The increased risk of misuse 
of infectious agents as weapons of terror, as well as 
instruments of warfare has prompted the Congress of the 
United States to pass statutes to protect the public from 
the illegitimate use of bacterial pathogens such as Bacillus 
anthracis, Yersinia pestis, Francisella tularensis, Coxiella 
burnetii, and Brucella species. 

Under normal circumstances, the incidence of naturally 
occurring infections caused by these bacterial pathogens is 
extremely low in the United States.  For this reason, the 
cadre of investigators conducting basic research on these 
agents is small and of limited scope. Substantial gaps in 
our knowledge concerning mechanisms involved in host 
immune/defense responses and pathogenesis exists. 
Specifically directed research is essential in order to 
devise appropriate protective strategies that could be 
implemented soon after– or shortly before - a bioterrorist 
incident.    

Research Objectives and Scope

Research proposals submitted in response to this RFA must 
demonstrate that they are relevant to one or more of the 
following objectives:

o  Identification and characterization of key biochemical, 
molecular, or genetic processes (or factors) that contribute 
to virulence, pathogenesis, and/or host 
resistance/susceptibility with potential for use as 
candidate targets for new vaccines, drug intervention, or 
immunotherapy to limit in vivo growth or negate the 
deleterious effects of those bacterial pathogens described 
above.
o  Design of novel therapeutic strategies, that can be 
implemented soon after a bioterrorist event, to prevent the 
germination of bacterial spores in vivo (in the case of 
anthrax), arrest or interrupt the spread of infection in 
vivo, and/or neutralize -or block-the synthesis of toxins 
(or other microbial products) that damage host tissues early 
during infection.
o  Develop novel or improved candidate vaccines that will 
generate significant protective immunity against aerosol 
challenge within a relatively short period of time after 
immunization with a minimal number of doses, as well as 
define serologic correlates or measures of the degree of 
protective immunity.

Although appropriate animal models may be used to acquire 
and evaluate the experimental data obtained, the development 
of a new animal model should not be the major focus of a 
proposal submitted in response to this RFA.

Proposals on the development of methods for the rapid 
detection of these bacterial pathogens, as well as for the 
rapid diagnosis of the infections they elicit, would be of 
value in the development of a comprehensive response to 
bioterrorism. However, such proposals should be submitted 
for consideration and funding as Small Business Innovation 
Research (SBIR) or Small Business Technology Transfer (STTR) 
grants, not in response to this RFA. 
   
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, 
compelling rationale, and justification are provided that 
inclusion is inappropriate with respect to the health of the 
subjects or 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", 
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 which is available via the 
WWW at: 
http://grants.nih.gov/grants/guide/notice-files/not94-100.html

NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS 
PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:

It is the policy of NIH that children (i.e., individuals 
under the age of 21) must be included in all human subjects 
research, conducted or supported by the NIH, unless there 
are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications  
submitted for receipt dates after October 1, 1998.

All investigators proposing research involving human 
subjects should read the "NIH Policy and Guidelines on the 
Inclusion of Children as Participants in Research Involving 
Human Subjects" that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and which is available 
at the following URL address: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html

Investigators may obtain copies from these sources or from 
Phillip J. Baker, Ph.D. (listed in INQUIRIES below) who may 
also provide additional relevant information concerning the 
policy.

LETTER OF INTENT

Prospective applicants are asked to submit, by December 10, 
1999, a letter of intent that includes a descriptive title 
of the overall proposed research; the name, address and 
telephone number of the Principal Investigator; and the 
number and title of this RFA.  Although the letter of intent 
is not required, is not binding, does not commit the sender 
to submit an application, and does not enter into the review 
of subsequent applications, the information that it contains 
allows NIAID staff to estimate the potential review workload 
and to avoid conflict of interest in the review.  The letter 
of intent is to be sent to Madelon Halula, Ph.D. at the 
address listed under INQUIRIES.

APPLICATION PROCEDURES

Applicants are strongly encouraged to call NIAID program 
staff with any questions regarding the responsiveness of 
their proposed project to the goals of this RFA.  

The modular grant concept establishes specific modules in 
which direct costs may be requested as well as a maximum 
level for requested budgets. Only limited budgetary 
information is required under this approach.  The 
just-in-time concept allows applicants to submit certain 
information only when there is a possibility for an award. 
It is anticipated that these changes will reduce the 
administrative burden for the applicants, reviewers and 
Institute staff.  The research grant application form PHS 
398 (rev. 4/98) is to be used in applying for  these grants, 
with the modifications noted below.

BUDGET INSTRUCTIONS


Modular Grant applications will request direct costs in 
$25,000 modules. For R03 applications an annual maximum 
direct cost of $50,000 may be for up to three years.  R01s 
requesting up to a total direct cost request of $250,000 per 
year must use the modular application format. Applications 
that request more than $250,000 direct costs in any year 
must follow the traditional PHS398 application instructions. 

For modular grant applications, the total direct costs must 
be requested in accordance with the program guidelines and 
the modifications made to the standard PHS 398 application 
instructions described below:

PHS 398

o FACE PAGE: Items 7a and 7b should be completed, indicating 
Direct Costs (in $25,000 increments up to a maximum of 
$250,000) and Total Costs [Modular Total Direct plus 
Facilities and Administrative (F&A) costs] for the initial 
budget period Items 8a and 8b should be completed indicating 
the Direct and Total Costs for the entire proposed period of 
support.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not 
complete Form Page 4 of the PHS 398. It is not required and 
will not be accepted with the application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not 
complete the categorical budget table on Form Page 5 of the 
PHS 398. It is not required and will not be accepted with 
the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant 
Budget Narrative page. (See 
http://grants.nih.gov/grants/funding/modular/modular.htm for sample pages.) At
the 
top of the page, enter the total direct costs requested for 
each year.  This is not a Form page.

o Under Personnel, List key project personnel, including 
their names, percent of effort, and roles on the project. No 
individual salary information should be provided. However, 
the applicant should use the NIH appropriation language  
salary cap and the NIH policy for graduate student 
compensation in developing the budget request.

For Consortium/Contractual costs, provide an estimate of 
total costs (direct plus facilities and administrative) for 
each year, each rounded to the nearest $1,000. List the 
individuals/organizations with whom consortium or 
contractual arrangements have been made, the percent effort 
of key personnel, and the role on the project. Indicate 
whether the collaborating institution is foreign or 
domestic. The total cost for a consortium/contractual 
arrangement is included in the overall requested modular 
direct cost amount.  Include the Letter of Intent to 
establish a consortium.

Provide an additional narrative budget justification for any 
variation in the number of modules requested.

o BIOGRAPHICAL SKETCH - The Biographical Sketch provides 
information used by  reviewers in the assessment of each 
individual's qualifications for a specific role in the 
proposed project, as well as to evaluate the overall 
qualifications of the research team. A biographical sketch 
is required for all key personnel, following the 
instructions below. No more than three pages may be used for 
each person. A sample biographical sketch may be viewed at:  
http://grants.nih.gov/grants/funding/modular/modular.htm
- Complete the educational block at the top of the form 
page;
- List position(s) and any honors;
- Provide information, including overall goals and 
responsibilities, on research projects ongoing or completed 
during the last three years.
- List selected peer-reviewed publications, with full 
citations;

o CHECKLIST - This page should be completed and submitted 
with the application. If the facilities and administation 
(F&A) rate agreement has been established, indicate the type 
of agreement and the date. All appropriate exclusions must 
be applied in the calculation of the F&A costs for the 
initial budget period and all future budget years.

o The applicant should provide the name and phone number of 
the individual to contact concerning fiscal and 
administrative issues if additional information is necessary 
following the initial review. 

Applications are to be submitted on the grant application 
for PHS 398 (rev. 4/98).  These forms are available at most 
institutional offices of sponsored research; from the 
Division of Extramural Outreach and Information Resources, 
National Institutes of Health, 6701 Rockledge Drive, MSC 
7910, Bethesda, MD 20892-7910, telephone 301/435-0714, 
email: grantsinfo@nih.gov; and on the internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html

For purposes of identification and processing, item 2a on 
the face page of the application must be marked "YES" and 
the RFA number "AI-99-014" and the words "PREPAREDNESS 
AGAINST ILLEGITIMATE USE OF BACTERIAL PATHOGENS" must be 
entered on the face page.

The RFA label and line 2 of the application should both 
indicate the RFA number.  The RFA label must be affixed to 
the bottom of the face page.  Failure to use this label 
could result in delayed processing of the application such 
that it may not reach the review committee in time for 
review.

The sample RFA label available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has 
been modified to allow for this change.  Please note this is 
in pdf format.

Applications must be received by January 19, 2000.  
Applications not received as a single package on the receipt 
date or not conforming to the instructions contained in PHS 
398 (rev. 4/98) Application Kit (as modified in, and 
superseded by, the special instructions below, for the 
purposes of this RFA), will be judged non-responsive and 
will be returned to the applicant. 

If the application submitted in response to this RFA is 
substantially similar to a grant application already 
submitted to the NIH for review, but that has not yet been 
reviewed, the applicant will be asked to withdraw either the 
pending application or the new one.  Simultaneous submission 
of identical applications will not be allowed, nor will 
essentially identical applications be reviewed by different 
review committees.  Therefore, an application that is 
essentially identical to one that has already been reviewed 
cannot be submitted in response to this RFA.  This does not 
preclude the submission of substantial revisions of 
applications already reviewed, but such applications must 
include an introduction addressing the previous critique.

Submit a signed, typewritten original of the application, 
including the checklist, and three signed, exact, single-
sided photocopies, in one package 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 mail or courier service)

At the time of submission, two additional exact copies of 
the grant application and all five sets of any appendix 
material must be sent to Madelon Halula at the address 
listed under INQUIRIES.

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 should be included with the 
application.

REVIEW CONSIDERATIONS  

Upon receipt, applications will be reviewed for completeness 
and adherence to the Special Instructions above by the NIH 
Center for Scientific Review and for responsiveness by NIAID 
staff; those judged to be incomplete or not in the format 
specified in this RFA will be returned to the applicant 
without review. Those considered to be non-responsive will 
be returned without review.

Applications that are complete and responsive to the RFA 
will be evaluated for scientific and technical merit by an 
appropriate peer review group convened by NIAID in 
accordance with the review criteria stated below.  As part 
of the initial merit review, a process will be used by the 
initial review group in which all applications will receive 
a written critique but only those applications deemed to 
have the highest scientific merit will be discussed, 
assigned a priority score, and receive a second level review 
by the National Advisory Allergy and Infectious Diseases 
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?

In addition to the above criteria, in accordance with NIH 
policy, all applications will also be reviewed with respect 
to the following:

o  The adequacy of plans to include both genders, minorities 
and their subgroups, and children as appropriate for the 
scientific goals of the research.  Plans for the recruitment 
and retention of subjects will also be evaluated.

o  The reasonableness of the proposed budget and duration in 
relation to the proposed research

o  The adequacy of the proposed protection for humans, 
animals or the environment, to the extent they may be 
adversely affected by the project  proposed in the 
application.

The personnel category will be reviewed for appropriate 
staffing based on the requested percent effort. The direct 
costs budget request will be reviewed for consistency with 
the proposed methods and specific aims. For modular grant 
applications, any budgetary adjustments recommended by the 
reviewers will be in $25,000 modules. The duration of 
support will be reviewed to determine if it is appropriate 
to ensure successful completion of the requested scope of 
the project.

AWARD CRITERIA
  
Funding decisions will be made on the basis of scientific 
and technical merit as determined by peer review, program 
balance, and the availability of funds.  The earliest 
anticipated date of award is September 15, 2000.

INQUIRIES  
  
Written and telephone inquiries concerning this RFA are 
encouraged.  The opportunity to clarify any issues or 
questions from potential applicants is welcome.

Direct inquiries regarding programmatic (research scope and 
eligibility) issues to:  

Phillip J. Baker, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
6700-B Rockledge Dr., MSC 7630, Room 3114
Bethesda, MD  20892-7630
Telephone:  (301) 435-2855
FAX:  (301) 402-2508
E-Mail:  pb26o@nih.gov
  
Direct inquiries regarding review issues and special 
instructions for application preparation; address the letter 
of intent to; and mail two copies of the application and all 
five sets of appendices to:
  
Madelon Halula, Ph.D.  
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
6700-B Rockledge Dr., MSC 7616, Room 2150
Bethesda, MD  20892-7616
Telephone:  (301) 402-2636
FAX:  (301) 402-2638
E-Mail: mh30x@nih.gov

Direct inquiries regarding fiscal matters to:  

Annette Hanopole
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
6700-B Rockledge Dr., MSC 7614, Room 2122
Bethesda, MD  20892-7614
Telephone:  (301) 496-7075
Fax: (301) 480-3780
E-mail:  ahanopole@niaid.nih.gov

Schedule

Letter of intent receipt date: December 10, 1999  
Application receipt date:      January 19 2000
Scientific review date:        May, 2000
Advisory Council date:         June,2000
Earliest award date:           September, 2000

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 
Citations are Sec. 93.856, Microbiology and Infectious 
Diseases Research, and No. 93.855 - Immunology, Allergy, and 
Transplantation Research.  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 Public Health Service 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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