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.


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