PAR-00-072: INTEGRATED PRECLINICAL / CLINICAL AIDS VACCINE DEVELOPMENT PROGRAM

Department of Health
and Human Services (HHS)

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INTEGRATED PRECLINICAL/CLINICAL AIDS VACCINE DEVELOPMENT PROGRAM Release Date: March 6, 2000 PA NUMBER: PAR-00-072 National Institute of Allergy and Infectious Diseases Application Receipt Dates: June 13, 2000, 2001, 2002. APPLICATIONS IN RESPONSE TO THIS PROGRAM ANNOUNCEMENT (PA) MUST BE PREPARED USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS FOR COMPLETING THE APPLICATION ARE IN THE NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS. PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) invites applications for research aimed at obtaining a safe and efficacious vaccine against HIV or AIDS. NIAID supports the progressive stages of AIDS vaccine research and development including basic research, iterative product development, and clinical trials. NIAID supports AIDS prophylactic vaccine research and development via three grant programs. The Innovation Grant Program for AIDS Vaccine Research supports high risk/high impact early stage concept evaluation for projects with limited preliminary data. The HIV Vaccine Research and Design (HIVRAD) Program supports multi-project investigator-initiated HIV vaccine design and development research. The Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) Program supports iterative product development and optimization in the later stages of vaccine research and includes limited human studies. This Program Announcement (PA) replaces PAR-97-056 and is a continuation of the Integrated Preclinical/Clinical AIDS Vaccine Development Program. For an overview of these research programs and other information, visit the NIAID AIDS Vaccine Research Website at: http://www.niaid.nih.gov/daids/vaccine/default.htm 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 PA, INTEGRATED PRECLINICAL/CLINICAL AIDS VACCINE DEVELOPMENT PROGRAM , is related to the focus area(s) of immunization and infectious diseases, HIV infection, and sexually transmitted diseases. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople ELIGIBILITY Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. In accordance with NIH policy, foreign institutions are not eligible for Program Project Grant (P01) awards. However, for this initiative, NIAID has been granted an exception. Foreign institutions may apply for grants under this Program Announcement however all other restrictions on foreign grant applications will apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISMS OF SUPPORT Program project grant (P01) applications may be submitted in response to this announcement. Program project grants support broadly based, multidisciplinary research programs that have a well-defined, central research focus or objective. An important feature is that the interrelationships of the individual scientifically meritorious projects will result in a greater contribution to the overall program goals than if each project were pursued individually. Standard NIH policy requires P01 applications to consist of a minimum of three interrelated individual research projects that contribute to the program objective. This type of award also can provide support for certain common resources termed cores. Such resources should be utilized by two or more projects within the award. An exception to standard policy has been granted for this program announcement such that fundable applications must have at least two (2) projects and one core. The total project period for P01 grants may not exceed five years. Responsibility for the planning, direction, and execution of the proposed research will be solely that of the applicant. Applicants for P01 grants must follow special application guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS (April 1999); this brochure is available via the WWW at: http://www.niaid.nih.gov/ncn/grants/multibron.htm In the case of any discrepancies, this PA will supercede the instructions in the Brochure. RESEARCH OBJECTIVES Background Vaccine research requires contributions from multiple fields including immunology, virology, animal models, and molecular biology. The IPCAVD program aims to foster the later stages of AIDS vaccine development that includes the transition of promising concepts from laboratory to clinic. Research Objectives and Scope As stated above, the overall goal of this PA is to support multidisciplinary research that will lead to a safe and protective AIDS vaccine. As such, IPCAVD applications must include human clinical studies within the term of the award. Studies responsive to this PA can include, but are not limited to: vaccine delivery and vector systems; methods of enhancing specific immune responses; dissection of viral and host contributions to immunity and combinations of these. Research directed toward optimization of existing vaccine concepts is also encouraged. Applications can include preclinical research, vaccine production, and clinical testing. However, preclinical research alone, without clear, feasible, and realistic plans for progressing to human testing within the period of award, will not be considered responsive to this PA. Applicants must delineate discrete goals, milestones, and criteria that can be used to evaluate progress toward a testable vaccine. If preclinical evaluation of the concept, according to these milestones, demonstrates that further studies should not be pursued, funding for those latter phases of the project will not be released. Applicants may also request funds for production of clinical grade (manufactured under Food and Drug Administration (FDA)-Good Laboratory Practices (GLP) guidelines) vaccine and subsequent in vivo testing. Applicants seeking to move from preclinical research to lot production must detail the goals, milestones, and criteria, which will be reviewed by the Scientific Review Group (SRG), to justify the release of funds for this purpose. Since human studies will require the filing of an IND application with the FDA, certain regulatory requirements must be met prior to the release of funds to initiate this part of the study. Additionally, information that may be useful in improving or refining the vaccine may arise during these clinical studies. The applicant should address how the results of the clinical evaluations will be used to either improve the vaccine concept or advance it through further human testing. Applicants must address the following issues in their application regarding human studies: design of the clinical trial, plans for recruitment, enrollment, education and follow-up of clinical subjects, including attention to the possibility of social harms and discrimination arising from vaccine- induced positive screening tests that may be interpreted incorrectly as HIV infection, plus documentation of compliance with all applicable federal (FDA), state and local laws and regulations governing clinical research. The completeness and feasibility of these plans will be reviewed by the SRG. Investigators are encouraged to discuss clinical evaluation of their candidate vaccines by the NIAID-supported HIV Vaccine Trials Network (HVTN) with NIAID Program Staff. For clinical trials, NIAID Program Staff can arrange for review of data by the AIDS Vaccine Data and Safety Monitoring Board, which reviews data for HVTN trials. Funds available under this PA are for small-scale early phase clinical studies. Investigators interested in pursuing NIAID support for large-scale human vaccine trials should contact the HVTN (see below for contact information). Vaccine research focused solely on therapeutic application is not responsive to this announcement. The safety evaluation of immunogens in infected animals or people may be included if these studies directly support the development of a prophylactic vaccine. For information on programs that support therapeutic vaccine development please contact program staff. The participation of the private sector is strongly encouraged because of its unique infrastructure, experience in product manufacture and development, and capital resources. These capabilities are considered to be especially appropriate and valuable for collaborative studies in this area. For example, a pharmaceutical or biotechnology company might participate in an individual project that provides testing of a preclinical concept and sufficient production of a vaccine when the product is needed to conduct studies. SPECIAL REQUIREMENTS All awardees are strongly encouraged to attend an NIAID-sponsored annual meeting on AIDS vaccine research and development and may include a request for travel funds for this purpose. Patent Coverage Since applications may involve several institutions, including the private sector, complex patent situations may arise. To avoid delays in the implementation of new vaccines for HIV related to intellectual property issues, each multi-project group is to provide a plan as part of the application, detailing 1) the approach, agreed to by all parties, to be used for obtaining patent coverage and for licensing, where appropriate, and, 2) the procedures to be followed for the resolution of legal problems that potentially may develop. Attention is drawn to the reporting requirements of 35 U.S.C. Parts 200-212 and 37 CFR Part 401 or FAR 55.227-11. Instructions were also published in the NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 19, No. 23, June 22, 1990. Note that non-profit organizations (including universities) and small business firms retain the rights to any patent resulting from Government grants or cooperative agreements. It is also noted that a Presidential memorandum of February 18, 1983, extended to all business concerns, regardless of size, the first option to the ownership of rights to inventions as provided in P.L. 96-517. As a result of this memorandum, the relationships among industrial organizations and other participants are simplified, since all Group members can now be full partners in the research and in any inventions resulting there from. The specific patenting arrangements among the institutions may vary and could include joint patent ownership, exclusive licensing arrangements, etc. Applicants are encouraged to develop an arrangement that is most suitable for the Group's particular circumstances. The agreement among the institutions comprising the Group, signed and dated by the organizational officials authorized to enter into patent arrangements for each Group member and member institution, must be delivered prior to submission of the application to Dr. Steve Bende, at the address listed under INQUIRIES. A copy of the patent agreement should also be submitted with the application. If the Group wishes to place all inventions and discoveries resulting from these studies within the public domain, a letter to that effect must be submitted to Dr. Bende in lieu of the patent agreement. The letter must be co-signed by the Principal Investigator, each of the Project Leaders, and each of the business officials representing the respective institutions. Federal regulation clause 37-CFR-401 and HHS Inventions regulations at 45 CFR Parts 6 and 8 require that NIH be informed of inventions and licensing occurring under NIH funded research. Invention and licensing reports must be submitted to the Extramural Invention Reports Office at 301 435 1986. Terms of Award On February 24, 2000, NIAID announced its expanded policies on MONITORING OF CLINICAL TRIALS AND STUDIES in the NIH Guide at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-00-003.html. Applications and awards with component clinical trials and studies must adhere to these policies including the terms and conditions of award; see http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf Phased Release of Funds: For awards including vaccine pilot lot production, release of funds for this purpose will be contingent on successful accomplishment of milestones and criteria proposed by the applicant. Release of funds for clinical research will be contingent on successful accomplishment of milestones and criteria for preclinical evaluation of the product and plans for its production and availability of funds. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear, compelling rationale, and justification are provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", published in the Federal Register of March 28, 1994 (FR 59 14508- 14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994 which is available at: http://grants.nih.gov/grants/guide/notice-files/not94-100.html INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and which is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators may obtain copies from these sources or from Dr. Steve Bende (listed in INQUIRIES below) who may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Applicants for P01 grants must follow special application guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS (April 1999); this brochure is available at: http://www.niaid.nih.gov/ncn/grants/multibron.htm Where differences exist, instructions in this Program Announcement take precedence over instructions in the Multi-Project Awards Brochure, which takes precedence over the standard PHS 398 instructions. The research grant application form PHS 398 (rev. 4/98) is to be used in applying for these grants. Application kits are available at most institutional offices of sponsored research and from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435- 0714, email: Grantsinfo@nih.gov Applications are also available at: http://grants.nih.gov/grants/forms.htm. All applications in response to this PA must include detailed rather than modular budgets. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the PA number as stated on the title page of this Program Announcement and the words "INTEGRATED PRECLINICAL/CLINICAL AIDS VACCINE DEVELOPMENT PROGRAM" must be typed in. Applications must be received by June 13 of the 3 years of the PA. 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. 4/98) Application Kit (as modified in, and superseded by, the NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS"), will be judged non-responsive and will be returned to the applicant. It is required that the appropriate NIAID program contact be consulted before submitting the application to obtain approval for acceptance of applications requesting direct costs $500,000 or more in any year of the proposed grant. (See program contact under INQUIRIES). Submit a signed, typewritten original of the application, including the checklist; the original of the appendices (if any); and three signed, exact, single-sided photocopies of the application (no copies of the appendices), in one package to: Center for Scientific Review National Institutes of Health 6701 Rockledge Drive, Room 1040 - MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express mail or courier service) At the time of submission, two additional exact copies of the grant application and all five copies of any appendix materials must be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. Concurrent submission of an R01 and a Component Project of a Multi-project Application: Current NIH policy permits a component research project of a multi-project grant application to be concurrently submitted as a traditional individual research project (R01) application. If, following review, both the multi-project application and the R01 application are found to be in the fundable range, the investigator must relinquish the R01 and will not have the option to withdraw from the multi-project grant. This is an NIH policy intended to preserve the scientific integrity of a multi-project grant, which may be seriously compromised if a strong component project(s) is removed from the program. Investigators wishing to participate in a multi-project grant must be aware of this policy before making a commitment to the Principal Investigator and awarding institution. GCRC INSTITUTIONS Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director must be included in the application material. REVIEW CONSIDERATIONS Review Procedures Applications will be assigned to NIAID on the basis of established NIH referral guidelines. Upon receipt, applications will be reviewed for completeness by the NIH Center for Scientific Review. Incomplete applications will be returned to the applicant without further consideration. P01 applications that are complete and responsive to this PA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIAID. Review Criteria The NIAID brochure "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS (April 1999) states the general review criteria for P01 applications. Additional review criteria specific to this PA are: For preclinical evaluation of vaccine concepts/strategies reviewers will consider: A. The overall scientific and technical merit of the proposed vaccine study with regard to impact on the AIDS epidemic. B. Appropriateness and adequacy of the experimental approach and the methodology proposed to carry out the research, specifically including the feasibility of the applicant's plans, and the availability of necessary facilities to conduct the research. In addition, the goals and milestones to be met for progression through to production and in vivo trial will be reviewed for adequacy, feasibility, and likelihood of attainment during the period of the grant. For production of clinical grade vaccine product, reviewers will consider: A. Appropriateness of the scientific rationale for advancing to the vaccine production stage, and suitability of the proposed milestones and criteria to be attained in order to merit funding. The SRG will judge the suitability of such criteria. If satisfactory proof that these criteria and milestones have already been met is supplied, funds to produce vaccine product will be released at the time of grant award. B. Completeness and feasibility of the plan to produce the vaccine. This includes adherence to any and all federal (FDA), state, and local regulations for the production of clinical grade material. For clinical studies, reviewers will consider: A. Scientific, technical, and clinical significance and originality of the proposed research. B. The completeness of plans for the design of the clinical trial, plans for recruitment, enrollment, education and follow-up of clinical subjects. This includes the safety, monitoring, and possibility of social harms and discrimination arising from vaccine-induced positive screening tests that may be interpreted incorrectly as HIV infection, and other harms such as true HIV infection as the result of vaccination, and compliance with all applicable Federal, State and local laws and regulations governing clinical research will be reviewed by the SRG. Appropriateness of the proposed criteria and milestones to be met to permit release of funds and progression of the study to the clinical phase. For all applications: A. Leadership and research experience of the Principal Investigator and key staff in the areas of proposed research. For clinical-grade vaccine production, the track record and facilities of the proposed producer. For clinical trials research, the leadership, scientific ability and administrative competence of the applicant for the development, implementation and management of pilot clinical trials, and for effective interaction with designated NIAID staff. B. Adequacy of the proposed means for protecting against adverse effects of the research upon humans, animals or the environment, where such are involved. C. Justification of the usefulness of the core facilities to the various research projects, including the administrative core, if applicable. Each core unit must provide essential facilities or service for two or more approved individual projects. D. A sound institutional administrative and organizational structure that facilitates attainment of the objective(s) of the program, including fiscal responsibility and management capability to assist the PI and staff in following PHS policy. The initial review group will also examine: the adequacy of plans to include children and both genders and minorities and their subgroups as appropriate for the scientific goals of the research and plans for the recruitment and retention of subjects. AWARD CRITERIA Applications will compete for available funds with all other favorably recommended applications. The following will be considered when making funding decisions: quality of the proposed project as determined by peer review, program balance among research areas of the announcement, and availability of funds. The NIAID gives special consideration for funding, including award of grants beyond the established NIAID percentile and priority score paylines, to scientifically meritorious applications in response to Program Announcements. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the NIAID brochure INSTRUCTIONS FOR APPLICATIONS FOR MULTI- PROJECT AWARDS as well as inquiries regarding programmatic (research scope, eligibility and responsiveness) issues may be directed to: Steve Bende, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases 6700-B Rockledge Drive, Rm. 4107, MSC 7628 Bethesda, MD 20892-7628 Telephone: (301) 435-3756 Fax: (301) 435-6511 Email: sb22k@nih.gov Direct inquiries regarding review issues to: Dr. Dianne Tingley Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6700-B Rockledge Dr. Room 2148, MSC 7616 Bethesda, MD 20892-7616 Bethesda, MD 20817 (for express/courier service) Telephone: (301) 496-0818 FAX: (301) 402-2638 Email: dt15g@nih.gov Direct inquiries regarding fiscal matters to: Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6700-B Rockledge Drive, Rm. 2128, MSC 7614 Bethesda, MD 20892-7614 Telephone: (301) 402-6824 Fax: (301) 480-3780 Email: ju3a@nih.gov Direct inquiries regarding the HVTN to: Dr. Jorge Flores Division of AIDS National Institute of Allergy and Infectious Diseases 6700-B Rockledge Drive, Rm. 4154, MSC 7628 Bethesda, MD 20892-7628 (301) Telephone: (301) 435-3758 Fax: (301) 435-6511 Email: jf30t@nih.gov AUTHORITY AND REGULATIONS This program is supported under authorization of the Public Health Service Act, Sec. 301 (c) and 405 (42 USC 241 and 284). The Catalogue of Federal Domestic Assistance Citations are Sec. 93.856, Microbiology and Infectious Diseases Research, and No. 93.855 - Immunology, Allergy, and Transplantation Research. Awards will be administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74 and 94. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems review. The Public Health Service strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or, in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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