BIODEFENSE PARTNERSHIPS:  VACCINES, ADJUVANTS, THERAPEUTICS, DIAGNOSTICS, AND 
RESOURCES

RELEASE DATE:  November 14, 2002 (see NOT-AI-03-006)

PA NUMBER: PAR-03-025 (see Notice of Early Termination NOT-AI-03-035)
                      (see replacement RFA-AI-03-016)

National Institute of Allergy and Infectious Diseases (NIAID) 
 (http://www.niaid.nih.gov) 

Letter of Intent Receipt Dates:  December 23, 2002 and May 10, 2003
Application Receipt Dates:  January 24, 2003 and June 10, 2003

THIS PAR CONTAINS THE FOLLOWING INFORMATION

o Purpose of this PAR
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations:

PURPOSE OF THIS PROGRAM ANNOUNCEMENT (PAR)

Research of the National Institute of Allergy and Infectious Diseases 
(NIAID), National Institutes of Health, strives to understand, treat and 
ultimately prevent the myriad infectious, immunologic, and allergic diseases 
that threaten millions of human lives.  The NIAID Division of Microbiology 
and Infectious Diseases (DMID) supports extramural research to control and 
prevent diseases caused by virtually all infectious agents. This includes 
basic biomedical research, such as studies of microbial physiology and 
antigenic structure; applied research, including the development of 
diagnostic tests; and clinical trials to evaluate experimental drugs and 
vaccines.  

In response to growing concerns about the use of biological agents in acts of 
terrorism, NIAID has identified a list of high priority products to be 
developed for biodefense that includes specific vaccines, adjuvants and 
immunostimulants, therapeutics, diagnostics, and clinical resources (see 
http://www2.niaid.nih.gov/Biodefense/Research/high_priority.htm) and is announcing 
this Partnership Grant Program to meet these needs. The objective of this 
grant program is to assist the private sector in the further development of 
these high priority products.  To be responsive to this program, the 
applicant must have already identified a candidate product or have 
demonstrated a proven technical approach or platform in one of the high 
priority areas and propose a plan for its further development.  Since the 
clinical development of new products spans a spectrum of activities, the 
further development of products conducted through this program may fall 
anywhere along a range of activities from characterization of the product, to 
preclinical evaluation and/or clinical studies (Phase I and/or Phase II 
clinical trials).  Applications should define the proposed project goal, 
interim objectives (development milestones), potential ultimate product(s) to 
be completed during the period of the grant, and provide a schedule or 
timeline for milestone and goal attainment.  Note:  Applications to support 
basic research or the "discovery" of new targets will not be supported under 
this initiative, but are supported by other NIAID biodefense programs (see 
http://www2.niaid.nih.gov/Biodefense/Research/funding.htm#B).

A key component of this initiative is the development of appropriate 
partnerships among government and the biotechnology, chemical, or 
pharmaceutical industries. For the purpose of this program, "industry" is 
defined as large and small, domestic or foreign, pharmaceutical, 
biotechnology, and chemical companies.  Since academic organizations are 
often the source of new candidate products, this program allows the 
partnering of industry with an academic or non-profit research organization; 
however, involvement of an academic or non-profit research organization is 
not a requirement.  All projects must demonstrate substantive involvement by 
a commercial sector (industry) component. "Substantive involvement" is 
defined, for the purpose of this program, as substantive commitment of any 
one or more of the following resources: funds, personnel, in kind 
contributions of materials and/or reagents, including but not limited to 
chemical libraries, innovative biotechnology platforms, (i.e. for screening 
of drugs and inhibitors), scale up GMP chemical synthesis or production, 
provision of animal or other laboratory models for evaluation, data 
management resources, and regulatory support. The Principal Investigator may 
be affiliated with any eligible institutions (see below).

PARTNERSHIPS

The Partnership Program is intended to support all phases of development of a 
candidate product or platform technology including, but not limited to, early 
validation, pre-clinical stages, scale-up, production, regulatory 
requirements, and, where appropriate, clinical or field evaluation. The NIAID 
recognizes that the inherent nature and demands of the product development 
process may require funding large, complex grants with interdependent 
specific aims. Furthermore, some aspects of the product development process 
(e.g., large-scale production of cGMP product) are inherently not innovative.  
Recognizing that product development is often an iterative and sequential 
process, and that steps early in the process may not be successful and may 
need to be modified or reworked, NIAID staff, through the cooperative 
agreement grant mechanism, will be actively involved in evaluating the 
milestones of awardees and determining whether additional investment in the 
development is warranted.

RESEARCH OBJECTIVES

Background

The National Institutes of Health and other agencies in the DHHS are 
currently supporting extramural and intramural projects to develop new 
products to protect the public from the health consequences resulting from 
the use of biological threat agents.  An NIAID Blue Ribbon Panel on 
Biodefense convened on February 4-5, 2002 identified the development of new 
vaccines, adjuvants, therapeutics, immunotherapeutics and diagnostics as one 
of the highest priorities (the full report can be found at: 
http://www2.niaid.nih.gov/biodefense/research/biotresearchagenda.pdf).

Investment by the private sector in the development of biodefense products is 
essential but remains limited.  It is imperative that candidate vaccines, 
therapeutics, adjuvants, diagnostics and resources against selected 
infectious biological threat agents be developed as quickly as possible to 
reduce the threat of their use in acts of terrorism or war.  The interaction 
of industry or non-profit organizations with academic organizations (if 
applicable) and the Government is strongly encouraged to quickly transition 
candidate products through preclinical development and clinical testing and 
commercialization.  This Partnership Program will support the clinical 
development of specific high priority products beginning with the further 
characterization of the candidate through preclinical development and Phase I 
and/or Phase II clinical studies.  Applications in response to this program 
are limited to selected high priority products (see Research Goals and 
Objectives below).

Potential applicants should also be aware of other biodefense research programs at 
NIAID that have different research scopes and requirements from those solicited in 
this PAR, including programs for the discovery of new candidate vaccines, drug 
targets, and the characterization of innate immune molecules that may be used as 
adjuvants (see http://www2.niaid.nih.gov/Biodefense/Research/funding.htm#B). 

Research Objectives and Scope

To be responsive to this Program, BIODEFENSE PARTNERSHIPS:  VACCINES, ADJUVANTS, 
THERAPEUTICS, DIAGNOSTICS, AND RESOURCES, the application must:

o Address one of the NIAID high priority products for biodefense listed at 
http://www2.niaid.nih.gov/Biodefense/Research/high_priority.htm;
o Identify a candidate product or the demonstration of a proven technical 
approach or platform for further development; and,
o Demonstrate substantial involvement by a commercial sector (industry) component 
and focus on the further development of an ultimate product(s) or strategy for 
product development in one of the specified high priority areas.

VACCINES 

Vaccines are the most effective method of protecting the public against 
infectious diseases.  The development of candidate vaccines against 
biological threat agents that can be administered quickly and can elicit a 
protective response in a broad range of recipients is a high priority.  
Applications for vaccine development in response to this program are limited 
to the following areas:  vaccines against tularemia; plague vaccines; cell-
based smallpox vaccines; Rift Valley Fever vaccines; novel influenza 
vaccines, including cell culture-based and pandemic influenza vaccine 
strategies; and vaccines against botulinum toxin.  

Research approaches should begin with an identified target or vaccine 
candidate in one of the above areas and develop a sound scientific rationale 
for the progression of the candidate vaccine through the product development 
pathway.  Clinical development activities that can be supported under this 
program include, but are not limited to, the following areas:

o Validation of protective epitopes or antigens;
o Optimization of production methodology;
o Scale up and production of candidate vaccines including GMP production;
o Optimization of delivery platforms;
o Evaluation of vaccine candidates formulated with or without adjuvants or 
immunodulators;
o Optimization of dose and route of delivery in pre-clinical evaluation;
o Performing preclinical testing for safety and efficacy in animal models and 
other benchmarks required for moving candidate vaccines into Phase I clinical 
trials;
o Optimization of safety and immunogenicity in Phase I clinical trials; and,
o Evaluation of dose-ranging and dosing intervals in Phase II clinical 
trials, including human challenge studies as appropriate.

Applications should focus on the further clinical development and testing of 
candidate vaccines identified in one of the above areas deemed responsive to 
this program.  The application should include a sound scientific rationale 
for the clinical development of the product.  A research and development plan 
must be included that defines the proposed project goal, interim objectives 
(development milestones) and potential ultimate product, and provides a 
schedule or timeline for milestone and goal attainment.

ADJUVANTS

The development of enhanced immune responses against biological threat agents 
may require the administration or co-administration of an adjuvant or 
immunostimulatory compound.  Applications to support the further clinical 
development or evaluation of molecules with documented ability to enhance the 
immune response or immunoregulation are responsive to this program, and 
products capable of enhancing an innate immune response in the lungs or the 
gastrointestinal tract are particularly encouraged. 

This program supports the further clinical development of vaccine adjuvants 
and immunomodulators against all NIAID Category A, B, and C priority 
pathogens that have previously been shown to have promise in early stages of 
development.  The types of adjuvants or immunomodulators that can be 
supported under this initiative include, but are not limited to, particulate 
materials (vaccine delivery systems), cytokines, chemokines, or costimulatory 
molecule expression, and innate immune receptor/ligand leads 
(immunostimulatory adjuvants).  Applications that focus on adjuvants known to 
increase the bioavailability of vaccine antigens (e.g., emulsions, 
microparticles, iscoms, and liposomes) or that target associated antigens to 
antigen presenting cells, and immunostimulatory adjuvants (e.g., LPS, MLP, or 
CpG DNA) that directly activate innate immune responses are also of 
particular interest.  Applications may propose the further clinical 
development of an adjuvant or immun0modulator as either a stand-alone product 
or in conjunction with a licensed or investigational vaccine against a NIAID 
Category A, B, or C priority pathogen.  

Clinical development activities supported under this program may include, but 
are not limited to, one or more of the following areas:

o Analysis of lead compounds based upon previous studies of their antigen 
targeting capability, receptor binding capacity, or effect on immune 
signaling; 
o Testing of previously-evaluated adjuvants for their capacity to stimulate 
enhanced immune responses toward specific NIAID category A, B or C priority 
pathogens/toxins; 
o Testing mixtures of adjuvants to evaluate additive or synergistic potential 
to stimulate desired immune responses;
o GMP production of candidate adjuvants or immunomodulators;
o Optimization of delivery platform(s), including antigen and adjuvant 
combinations/formulations;
o Optimization of dose, dosing interval, and route of delivery in pre-
clinical evaluation;
o Performing preclinical testing for safety and efficacy in animal models and 
other benchmarks required for moving candidate adjuvants into Phase I 
clinical trials;
o Optimization of safety and immunogenicity in Phase I clinical trials; and,
o Evaluation of dose-ranging and dosing interval Phase II clinical trials, 
including human challenge studies as appropriate.

Applications should focus on the further clinical development and testing of 
a candidate adjuvant or immunomodulator identified in one of the above areas 
deemed responsive to this program.  The application should include a sound 
scientific rationale for the clinical development of the product.  A research 
and development plan must be included that defines the proposed project goal, 
interim objectives (development milestones) and potential ultimate product, 
and provides a schedule or timeline for milestone and goal attainment.

THERAPEUTICS

The need for safe and effective, broad-spectrum and specific, antimicrobials 
for biodefense against threats by highly pathogenic agents or their toxins is 
a key national priority.  Applications for development of the following 
products are responsive under this program: novel antivirals against all 
NIAID Category A, B, and C priority pathogens, (particularly encouraged are 
antiviral agents against smallpox and viral hemorrhagic fevers); antitoxins 
to B. anthracis and C. botulinum; narrow-spectrum antibiotics against 
anthrax; passive immunotherapies against any NIAID category A, B, or C 
priority pathogens; and broad spectrum antimicrobials. The further 
characterization of immunotherapeutics such as antimicrobial peptides, 
lectins, or immune modulators with broadly protective or pathogen-specific 
potential and novel antibodies shown to have high specificity for antigens 
from NIAID category A, B, or C priority pathogens is also responsive.

Activities to support the further clinical development of previously 
identified drug candidates may include but are not limited to, one or more of 
the following areas:

o Performing molecular modeling and/or library screening to optimize 
candidate compounds for preclinical studies;
o Synthesis of sufficient quantities of a lead compound(s) for in vitro 
analysis;
o Performing reiterative design, chemical synthesis and in vitro analysis to 
develop a "mature" lead compound;
o Performing preliminary pharmacokinetics and pharmacodynamics; assessing 
bioavailability and mechanism of action;
o Evaluating the potential for the emergence of drug resistance in model 
systems;
o Synthesizing, purifying, and testing drugs/inhibitors for efficacy and 
toxicity in model assays and preclinical in vivo systems; 
o Determining drug interactions in host molecular processes;
o Performing required benchmarks for moving a drug candidate into Phase I 
clinical trials (http://www.fda.gov/cder/regulatory/default.htm);
o Optimization of safety in Phase I clinical trials; and,
o Evaluation of dose-ranging and dosing interval in Phase II clinical trials, 
including human challenge studies as appropriate.

Applications should focus on the further clinical development and testing of 
a candidate therapeutic identified in one of the above areas deemed 
responsive to this program.  The application should include a sound 
scientific rationale for the development of the product.  A research and 
development plan must be included that defines the proposed project goal, 
interim objectives (development milestones) and potential ultimate product, 
and provides a schedule or timeline for milestone and goal attainment.

DIAGNOSTICS 

There is an urgent need for rapid, highly sensitive, specific, easy to use, 
and cost-effective diagnostics for public health laboratories and point-of-
care use to identify or diagnose individuals exposed to biological threat 
agents or their toxins. Diagnostics tools that will rapidly distinguish early 
infection by a biological threat agent from common infections with similar, 
generalized symptoms and determine drug sensitivity of the agent are also of 
high priority. 

This program supports the further development of sensitive, specific, and 
rapid diagnostics and/or diagnostic methods against all NIAID Category A, B, 
and C priority pathogens, and of platforms that can distinguish these 
pathogens from common infections.  It is anticipated that applications will 
focus on technologies that have previously been shown to have promise in 
early stages of development.  

Applications that focus on the following areas are particularly encouraged:

o Tests to evaluate antimicrobial resistance, enhanced virulence, or genetic 
manipulation;
o Tests capable of high throughput screening (e.g. microchip-based platforms) 
containing microbial signature profiles;
o Tests capable of identifying multiple pathogens simultaneously in a single 
sample;
o Novel assays based on human immune or other physiological responses;
o Tests capable of identifying novel biomarkers for human immune activation;
o In vivo imaging methods and development of contrast reagents for 
visualization of pathogens or host immune responses in vivo;
o Clinical diagnostic tools for human eczema; and,
o Diagnostics that can be used in remote settings.  

Applications should focus on the further development and validation of a 
diagnostic test or diagnostic method.  Preliminary data should be presented 
to support the basis of the method.  Capabilities of the diagnostics should 
be described.  Plans for determining the sensitivity, specificity and 
validation of the diagnostic should be included in the application.  The 
application should include a sound scientific rationale for the development 
of the product.  A research and development plan must be included that 
defines the proposed project goal, interim objectives (development 
milestones) and potential ultimate product, and provides a schedule or 
timeline for milestone and goal attainment.

RESOURCES

The availability of research resources and tools is often a critical 
component in the development of new vaccines, adjuvants, therapeutics, and 
diagnostics. Among the resources needed to conduct biodefense research are 
genomics, proteomics, appropriate in vitro and animal models, validated 
assays and standardized reagents. Applications for research resources in 
response to this PAR are limited to the following areas: 

o Vaccine delivery systems and platform technologies;
o Software development tools for genetic, genomic, and proteomic analysis and 
modeling of host-pathogen interactions;
o Screening tools and services for high throughput antigen identification;
o Appropriate standardized cell cultures and animal models for testing and 
development of vaccines;
o Validated assays needed for product licensure including assays to measure 
toxicity, safety, efficacy, immunogenicity and other host responses.

Applications should focus on the further development and testing of one of 
the above resources or tools deemed responsive to this program.  The 
application should include a sound scientific rationale for the development 
of the product.  A research and development plan must be included that 
defines the proposed project goal, interim objectives (development 
milestones) and potential ultimate product, and provides a schedule or 
timeline for milestone and goal attainment.

MECHANISM OF SUPPORT

This Partnership Program will use the NIH Cooperative Agreement (U01) grant 
mechanism.  Under a U01 grant mechanism, the Principal Investigator retains 
the primary responsibility and dominant role for planning, directing, and 
executing the proposed project, with NIH staff being substantially involved 
as a partner with the Principal Investigator, as described under the section 
"Cooperative Agreement Terms and Conditions of Award"

The total project period for applications submitted in response to this 
program may not exceed five years. 

FUNDS AVAILABLE

The estimated total funds [direct and facilities and administrative (F&A) 
costs] available for the first year of support for all awards made under this 
program will be $100 million in Fiscal Year 2003.  In Fiscal Year 2003, the 
NIAID plans to fund approximately 20-40 awards.  Funds available for additional 
competing awards in Fiscal Year 2004 have not yet been determined. To ensure 
that research aims can be met and biohazards can be contained, an applicant may 
request up to $500,000 for significant alterations and renovations and/or up to 
$300,000 for major equipment. Funds for these purposes MUST be included in the 
first year's requested budget.  Although this program is provided for in the 
financial plans of the NIAID, awards pursuant to this PAR 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.

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the 
following characteristics:

o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, hospitals, 
and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  

Both domestic and foreign organizations are eligible.  Institutions must be 
in compliance with U.S. laws and regulations and DHHS and NIH policies in 
effect at the time of grant award and during the period of performance of the 
research.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

All applications must include substantive involvement by industry (as defined 
above).  Any individual with the skills, knowledge, and resources necessary 
to carry out the proposed research is invited to work with their institution 
to develop an application for support.  Individuals from underrepresented 
racial and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS

Applications in response to this program are limited to the selected NIAID 
high priority products described above (under Research Objectives and Scope).  
Each application must propose a research and development project whose goal 
is to advance a specific vaccine, adjuvant, therapeutic, diagnostic, or 
research resource as specified above.  

Applications must propose clear project goal(s), including one (or more) 
final product(s) or stage(s) of development to be completed during the award 
period.  The applicant must clearly state the interim objectives 
(developmental milestones) to be achieved during the project, identify 
impediments or critical decision points that could require a revision in the 
work plan or milestones, and provide a detailed schedule or timeline for the 
attainment of each milestone and/or goal.  

Intellectual Property:  

The successful development of these high priority products for biodefense will 
require substantial involvement and support of private sector industries and 
may also involve collaborations with multiple organizations, including academic 
and/or non-profit research institutions.  It is the intent of this initiative 
to support the formation of the appropriate public-private partnerships that 
are essential to meet these urgent public health needs.  Intellectual property 
rights are likely to play an important role in achieving the goals of this 
program.  To this end, the NIAID requires that at the time of application all 
applicants must provide a letter ("Proprietary Rights Assurance Letter") 
containing the following assurances, which is signed by a representative who is 
duly authorized to provide such assurances on behalf of the applicant 
organization:

o Applicant is solely responsible for the timely acquisition of all 
proprietary rights, including intellectual property rights, and all materials 
needed for applicant to perform the project
o Applicant acknowledges that prior to, during, and subsequent to the award, 
the U.S. Government is not required to obtain for applicant any proprietary 
rights, including intellectual property rights, or any materials needed by 
applicant to perform the project
o Applicant acknowledges the requirement to report to the U.S. Government all 
inventions made in the performance of the project, as specified at 35 U.S.C. 
Sect. 202.

Apart from the Proprietary Rights Assurance Letter, applicants are expected 
to exercise their Bayh-Dole rights in a manner that does not conflict with 
the goals of this award or the intent of the Bayh-Dole Act to promote the 
utilization, commercialization and availability of U.S. Government-funded 
inventions for public benefit.  In addition, applicants are expected to make 
new information and materials known to the research community in a timely 
manner through publications, web announcements, reports to the NIAID or other 
mechanisms.

Select Agents: 

Applicants must state that the participating institutions are in compliance 
with Select Agent regulations (http://www.cdc.gov/od/sap/) and NIH 
Guidelines for Research Involving Recombinant DNA Molecules 
(http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html).

Phase I and/or Phase II Clinical Trials:

Any applicant proposing a project that contains or comprises a Phase I and/or 
Phase II clinical trial must submit a clinical protocol as part of the 
application, and a mandatory milestone that must be included is the approval 
of the final clinical protocol by NIAID.  Applicants must build this 
milestone into their application.   

For applications that contain or comprise a Phase I and/or Phase II clinical 
trial, the NIAID will also require the establishment of an Independent Safety 
Monitor (ISM), a Safety Monitoring Committee (SMC), or a Data and Safety 
Monitoring Board (DSMB), as deemed appropriate by NIAID, to monitor the 
safety of participants in the clinical trial(s).  Applicants proposing a 
project(s) that contains or comprises a clinical trial(s) should discuss this 
possibility with NIAID Program Staff before submission of the application.  
If a DSMB is required, funds to support and convene the DSMB must be included 
in the proposed budget.

For guidance on protocol format and/or other issues related to clinical 
studies and monitoring the safety of human subjects, applicants should 
contact the DMID Office of Clinical Research Affairs (Contact information is 
provided below).

Mandatory Meetings:

The Principal Investigator, one or two key personnel designated by the 
Principal Investigator, two external advisors, and the NIAID Program Officer 
will meet once a year to review progress and aid program development.  
Proposed budgets must include funds to travel the Principal Investigator, key 
personnel, and two external advisors (to be named after award by NIAID in 
consultation with the Principal Investigator) to an annual two-day meeting in 
Bethesda, Maryland, or at a relevant scientific meeting, as determined by 
NIAID Program staff.  Names of suggested external advisors should not be 
included in the application.

Informal Meetings:

A critical determinant of success of the project is likely to be the degree 
of communication among the grantee organization, any collaborating 
institutions (if applicable), and the NIH and/or other US government 
agencies.  Regular telephone and written communications on the status of 
progress among collaborators, including the NIAID Program Officer will be 
important and are strongly encouraged.

Where scientifically appropriate, NIAID may ask grant recipients to 
collaborate or cooperate with other NIAID funded projects and/or US 
government agencies, for example, the Food and Drug Administration, the 
Centers for Disease Control and Prevention, and the United States Department 
of Agriculture.

TERMS AND CONDITIONS OF AWARD

The following terms and conditions will be incorporated into the award 
statement and provided to the Principal Investigator as well as the 
institutional official at the time of award.

These special Terms of Award are in addition to, and not in lieu of, 
otherwise applicable OMB administrative guidelines, HHS Grant Administration 
Regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant 
Administration policy statements.

The administrative and funding instrument used for this program is the 
cooperative agreement (U01), in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during the 
performance of the activity.  Under the cooperative agreement, the NIH 
purpose is to support and/or stimulate the recipient's activity by 
involvement in and otherwise working jointly with the award recipient in a 
partnership role, but it is not to assume direction, prime responsibility, or 
a dominant role in the activity.  Consistent with this concept, the dominant 
role and prime responsibility for the activity resides with the awardees for 
the project as a whole, although specific tasks and activities in carrying 
out the research will be shared among the awardees and the NIAID Program 
Officer.  

1.  Clinical Terms of Award

When human subjects or human samples are a component of the research 
proposed, NIAID policy requires that studies be monitored commensurate with 
the degree of potential risk to human subjects.  Terms and Conditions of 
Award will be included with awards. The NIAID policy including terms and 
conditions of award is available at: 
http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf.

2.  Awardee Rights and Responsibilities

Awardees may be from industry or academia; however, the industrial portion of 
the partnership is critical for compliance and substantive involvement by 
industry directed to the specific project being proposed must be clearly 
defined.  

Awardees will have primary responsibility for defining the research 
objectives, approaches and details of the projects within the guidelines of 
the PAR and for performing the scientific activity. Specifically, awardees 
have primary responsibility as described below.

The awardee must be in compliance with Select Agent Rule 
(http://www.cdc.gov/od/sap/) and NIH Guidelines for Research 
Involving Recombinant DNA Molecules 
(http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html).

The Principal Investigator retains primary responsibility for the performance 
of the scientific activity, and agrees to accept close assistance in 
coordination, cooperation and participation of NIAID staff in scientific and 
technical management of the project in accordance with the terms formally and 
mutually agreed upon prior to the award.  The responsibility for the 
planning, direction, and execution of the proposed project will be solely 
that of the Principal Investigator.

For research conducted in foreign countries, the awardee must assure 
compliance with the host country regulations for human subjects, and must 
assure that the trials are conducted according to one of the following:  the 
US Federal Policy (Common Rule) for the Protection of Human Subjects and/or 
the US Department of Health and Human Services (HHS) regulations at 45 CFR 46   
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm; the May 
1, 1996 International Conference on Harmonization E-6 Guidelines for Good 
Clinical Practice (ICH-GCP-E6) Sections 1 through 4; The 1993 Council for 
International Organizations for Biomedical Research Involving Human Subjects; 
the 1998 Medical Research Council of Canada Tri-Council Policy Statement on 
Ethical Conduct for Research Involving Humans; the 2000 Indian Council of 
Medical Research Ethical Guidelines for Biomedical Research on Human 
Subjects; or other internationally recognized standards for the protection of 
human subjects.

Meetings: One mandatory progress review meeting of the awardees will be held 
annually at the NIH, or at a site designated by the NIH, during which the 
Principal Investigator and Project Leaders will present significant findings.  
The NIAID Program Officer and External Advisors (when applicable) will be 
present.  A critical determinant of success will be the degree of 
communication between the Principal Investigator, Project Leaders and other 
significantly involved parties. Therefore, in addition to the one meeting 
listed above, additional meetings, which may be necessary for coordination of 
cooperative agreement activities, may be scheduled if justified.  Regular 
telephone and written communication will be important and are encouraged.

Publications: The Principal Investigator will be responsible for the timely 
submission of all abstracts, manuscripts and reviews (co)authored by members 
of the grant and supported in part or in total under this Agreement.  The 
Principal Investigator and Project Leaders are requested to submit 
manuscripts to the Program Officer within two weeks of acceptance for 
publication so that an up-to-date summary of program accomplishments can be 
maintained and joint press conferences prepared.  Publications or oral 
presentation of work done under this Agreement is the responsibility of the 
Principal Investigator and appropriate Project Leaders and will require 
appropriate acknowledgement of NIAID support.  Timely publication of major 
findings is encouraged.

While the NIAID Program Officer has a right of access to the data (see NIAID 
staff responsibilities below) the awardee will retain custody of and right to 
the data. For more information on data sharing go to: 
http://grants.nih.gov/grants/policy/data_sharing/index.htm. 

3. NIAID Staff Responsibilities
     
The NIAID Program Officer will provide normal stewardship and will have 
substantial scientific/programmatic involvement during the conduct of this 
activity through technical assistance, advice and coordination above and 
beyond normal program stewardship for grants, as described below.

The NIAID Program Officer will serve as a liaison/facilitator between the 
awardee, pharmaceutical and biotech industries, and other government agencies 
(e.g., FDA, USDA, CDC), and will serve as a resource of scientific and policy 
information related to the goals of the awardee's research. The NIAID Program 
Officer will facilitate coordination of project activities during the course 
of the project.

The NIAID Program Officer will assist the awardee with access to other NIAID-
supported resources and services, including resources for preclinical 
development such as animal models, screening facilities, standardized 
research reagents, and a genomics resource center, where available.

3.  Collaborative Responsibilities

The specific timelines, interim objectives and funding levels agreed to by 
the awardee and the NIAID shall be included in the terms and conditions of 
award.  Given the nature of product development, it is recognized that 
timelines and interim objectives may require revision and renegotiation 
during the course of the project period.  The Principal Investigator and 
NIAID must agree to all such revisions. Release of each funding increment by 
NIAID will be based on a NIAID review of progress towards achieving the 
previously agreed upon interim objective.   Where scientifically appropriate, 
NIAID may ask recipients to collaborate or cooperate with other NIAID funded 
projects and/or US government agencies, for example CDC, FDA, and/or USDA.

4.  Arbitration

Any disagreement that may arise on scientific or programmatic matters (within 
the scope of the award) between award recipients and the NIAID may be brought 
to arbitration.  An arbitration panel composed of three members -- one 
selected by the Steering Committee or by the individual awardee in the event 
of an individual disagreement, a second member selected by the NIAID, and the 
third member with expertise in the relevant area and selected by the two 
prior members will be formed to review any scientific or programmatic issue 
that is significantly restricting progress.  While the decisions of the 
Arbitration Panel are binding, these special arbitration procedures will in 
no way affect the awardee's right to appeal an adverse action in accordance 
with PHS regulations at 42 CFR Part 50, subpart D, and HHS regulations at 45 
CFR Part 16.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PAR and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into four 
areas:  scientific/research, peer review, financial or grants management, and 
protocol format/clinical studies issues:

o Direct your questions about scientific/research issues on VACCINES to:

Dr. Linda Lambert
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
6610 Rockledge Drive, Room 6026
Bethesda, MD  20892-7630
Telephone:  301-496-5305
FAX:  301-496-8030
E-Mail: LL153p@nih.gov 

o Direct your questions about scientific/research issues on ADJUVANTS to:

Dr. Charles Hackett  
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases  
Room 5139, MSC-7640
6700-B Rockledge Drive
Bethesda, MD  20892-7640
Telephone:  (301) 496-7551
FAX:        (301) 402-2571
E-Mail: chackett@niaid.nih.gov 

o Direct your questions about scientific/research issues on THERAPEUTICS to:

Dr. Catherine Laughlin  
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room 3105, MSC-7630
6700-B Rockledge Drive
Bethesda, MD  20892-7630
Telephone:  (301) 496-7453
FAX:  (301) 480-1594
E-Mail:  cl28r@nih.gov

Dr. Alison Deckhut (IMMUNOTHERAPEUTICS) 
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases  
Room 5138, MSC-7640
6700-B Rockledge Drive
Bethesda, MD  20892-7640
Telephone:  (301) 496-7551
FAX:        (301) 402-2571
E-Mail:     ad122x@nih.gov

o Direct your questions about scientific/research issues on DIAGNOSTICS to:

Dr. Maria Giovanni
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
6610 Rockledge Drive, Room 6056
Bethesda, MD  20892-7630
Telephone:  301-496-5305
FAX: 301-496-8030
E-Mail:  Mgiovanni@niaid.nih.gov 

Dr. Robert Hall
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
6610 Rockledge Drive, Room 6009
Bethesda, MD  20892-7630
Telephone:  301-496-7051
FAX: 301-402-1456
E-Mail: Rhall@niaid.nih.gov

o Direct your questions about scientific/research issues on PLATFORM 
TECHNOLOGIES to:

Dr. Linda Lambert
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
6610 Rockledge Drive, Room 6026
Bethesda, MD  20892-7630
Telephone:  301-496-5305
FAX:  301-496-8030
E-Mail: LL153p@nih.gov 

o Direct your questions about PEER REVIEW issues; address the LETTER OF 
INTENT; and MAIL TWO COPIES OF THE APPLICATION and all FIVE SETS OF 
APPENDICIES to:

Dr. Dianne Tingley
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
Room, MSC-7616
6700-B Rockledge Drive  
Bethesda, MD  20892-7616
Telephone:  (301) 496-0818
FAX:    (301) 402-2638
E-Mail: dtingley@niaid.nih.gov

Direct inquiries regarding FISCAL MATTERS to:  

Ms Sharie Bernard  
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
Room 3219, MSC-7614
6700-B Rockledge Drive  
Bethesda, MD  20892-7614
Telephone:  (301) 402-5065
Fax:  (301) 480-3780
E-mail:  sb34k@nih.gov

o Direct inquiries regarding PROTOCOL FORMAT and/or other issues related to 
CLINICAL STUDIES to: 

Dr. Holli Hamilton
The Office of Clinical Research Affairs
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases  
Room Number 6026
6700-B Rockledge Drive
Bethesda, MD 20892-6603 
Telephone: (301) 496-7067 
FAX: (301) 480-0728
Email:  hhamilton@niaid.nih.gov 

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research including to which of the five 
general areas (vaccines, adjuvants, therapeutics, diagnostics, resources) you 
are responding;
o Name, address, and telephone number of the Principal Investigator;
o Names of other key personnel;
o Participating institutions; and,
o Number and title of this Program PAR.

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document to:

Dr. Dianne Tingley  
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
Room 2148, MSC-7610
6700-B Rockledge Drive  
Bethesda, MD  20892-7610 (20817 for express carriers)
Telephone:  301-496-2550
FAX: 301-402-2638
E-Mail: dtingley@niaid.nih.gov 

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.

Applications must also address each of the instructions described under the 
SPECIAL REQUIREMENTS section, as applicable.

APPLICATION RECEIPT DATES: Applications submitted in response to this program 
must be received by the dates listed on the first page.
 
Applications that are not received as a single package on the receipt date or 
that do not conform to the instructions contained in PHS 398 (rev. 5/01) 
Application Kit will be judged non-responsive and will be returned to the 
applicant.  

For purposes of identification and processing, item 2a on the face page of 
the application must be marked "YES," the PAR number and the words 
"BIODEFENSE PARTNERSHIPS:  VACCINES, ADJUVANTS, THERAPEUTICS, DIAGNOSTICS, 
AND RESOURCES" must be entered on the face page.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  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.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.

SENDING AN APPLICATION TO THE NIH: 

Submit a signed, typewritten original of the application, including the 
checklist, and three signed 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/courier service)

At the same time, mail two copies of the application and all five sets of 
appendices to:

Dr. Dianne Tingley  
Division of Extramural Activities  
National Institute of Allergy and Infectious Diseases  
Room 2148, MSC-7610
6700-B Rockledge Drive  
Bethesda, MD  20892-7610 (20817 for express carriers)
Telephone:  301-496-2550
FAX: 301-402-2638
E-Mail: dtingley@niaid.nih.gov 

APPLICATION PROCESSING:  Applications must be received by the dates listed on 
the first page.  The CSR will not accept any application in response to this 
Program that is essentially the same as one currently pending initial review 
unless the applicant withdraws the pending application.  The CSR will not 
accept any application that is essentially the same as one already reviewed.  
This does not preclude the submission of a substantial revision of an 
application already reviewed, but such application must include an 
Introduction addressing the previous critique.

It is highly recommended that the appropriate NIAID program staff be 
consulted before submitting the letter of intent and during the early stages 
of preparation of the application.  (See program contacts under INQUIRIES).

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIAID.

Incomplete or late applications will be returned to the applicant without 
further consideration. 
Applications that are complete and responsive to the PAR will be evaluated 
for scientific and technical merit by an appropriate peer review committee 
convened by NIAID in accordance with the review criteria stated below. As 
part of the initial merit review, all applications will:

o Receive a written critique
o Undergo a selection process in which only those applications deemed to have 
the highest scientific merit, generally the top half of applications under 
review, will be discussed and assigned a priority score
o Receive a second level review by the National Institute of Allergy and 
Infectious Diseases Council

Depending on the total number and research topics of applications received in 
response to this PAR, applications may be separated into subgroups for review 
by different peer review committees.

REVIEW CRITERIA

The 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.

o Significance
o Approach
o Innovation
o Investigator
o Environment

The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your 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, you may propose to carry out 
important work that by its nature is not innovative but is essential to move 
a field forward.  

1. SIGNIFICANCE:  Is this project likely to significantly advance the 
development of a vaccine, adjuvant, therapeutic, diagnostic, or research 
resource against the specific biologic threat agent identified in this 
initiative? If the aims of the application are achieved, are important 
biomedical agents or products likely to result?  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? Is the industry commitment adequate to have an impact on 
the success of the proposed research objectives? Is the likelihood of 
successful project completion high given the current state of research and 
development and the technical approach? Are the proposed timeline and interim 
milestones appropriate, feasible and technically sound? 

3. INNOVATION:  If appropriate, does the project employ novel concepts, 
approaches, or methods?  Are the aims original and innovative?  Does the 
project challenge existing paradigms or develop new methodologies or 
technologies?

4. INVESTIGATOR:  Is the research and development team appropriately trained 
and experienced 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)? Is there strong evidence of substantive industrial 
commitment?

5. ENVIRONMENT:  Does the 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 environments, including 
partnerships with industry, or employ useful collaborative arrangements?  Is 
there adequate evidence of institutional support?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed and evaluated with respect to the 
following:

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

o HUMAN SUBJECTS:  If you marked "Yes" for Item 4 on the Face Page of the 
application and did not claim any exemptions from the regulations, you  
create a section entitled "Protection of Human Subjects." In this section, 
you must provide information to address all four evaluation criteria listed 
at http://grants.nih.gov/grants/funding/phs398/instructions2/p1_specific
_instructions.htm#e_Human_Subjects_Research as they apply to the 
research you are proposing. Failure to address the above 
human subjects protection issues will result in the 
application being designated as incomplete and will 
be grounds for the PHS to return the application without peer review. 

o INCLUSION: The adequacy of plans to include subjects from both genders, all 
racial and ethnic groups (and subgroups), and children as appropriate for the 
scientific goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria included in the 
section on Federal Citations, below)

o DATA SHARING: The adequacy of the proposed plan to share data. 

o BUDGET: The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

AWARD CRITERIA

The following will be considered in making funding decisions: 

o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities
  
REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA AND SAFETY MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 clinical research projects unless a 
clear and compelling justification is provided indicating 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 clinical research should read the AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; 
and b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: 
The NIH maintains a policy 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 is available at 
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm and at  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide the official NIH 
identifier(s)for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This 
PAR is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople 

AUTHORITY AND REGULATIONS

This program is described in the Catalogue of Federal Domestic Assistance in 
the following citations: No. 93.855, Immunology, Allergy, and Transplantation 
Research and No. 93.856, Microbiology and Infectious Diseases Research. 
Awards are made under authorization of Sections 301 and 405 of the Public 
Health Service Act as amended (42 USC 241 and 284) and administered under NIH 
grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  
This program is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.

The NIH Grants Policy Statement is available at 
http://grants.nih.gov/grants/policy/policy.htm.  This document includes 
general information about the grant application and review process; 
information on the terms and conditions that apply to NIH Grants and 
cooperative agreements; and a listing of pertinent offices and officials at 
the NIH.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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