Full Text AI-94-011 BASIC BIOLOGY OF IMMUNE RESPONSES FOR VACCINE RESEARCH NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: AI-94-011 P.T. Keywords: National Institute of Allergy and Infectious Diseases National Institute on Aging Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: July 13, 1994 PURPOSE The Division of Allergy, Immunology and Transplantation (DAIT) of the National Institute of Allergy and Infectious Diseases (NIAID) and the Biology of Aging Program (BAP) of the National Institute on Aging (NIA) invite applications for basic studies designed to elucidate key processes underlying immune responsiveness that will facilitate new and improved approaches to vaccination for infectious diseases other than AIDS. There is increasing need to develop methods for achieving protective immunity that depend on manipulating elements of the immune system (e.g., the order, concentrations, and delivery of cytokines). There are numerous examples of potential vaccines that are ineffective because of weak immunogenicity that could become effective vaccines if properly presented to a prepared or modulated immune system. This Request for Applications (RFA) is intended to spur the acquisition of knowledge necessary to efficaciously and safely modulate elements of the immune system leading to protective immunization against infectious diseases. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Basic Biology of Immune Responses for Vaccine Research, is related to the priority areas of diabetes and chronic disabling diseases, and to immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanism of support will be the Program Project (P01) grant. Research that involves collaborative efforts among investigators in the fields of basic immunology, molecular biology, cell biology, biochemistry, and infectious disease is strongly encouraged. The total project period for applications submitted in response to this RFA may not exceed five years. At this time, the NIAID and the NIA are administratively limiting the duration of P01 grants to four years; this administrative limitation may change in the future. If by the beginning of the last year of support, the NIAID and the NIA have not announced their intention to readvertise the RFA, P01 incumbents who wish to recompete are strongly encouraged to contact NIAID and NIA Program Staff concerning selection of an appropriate research grant mechanism before reapplying. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for first year of support for all awards made under this RFA will be $3,000,000. In Fiscal Year 1995, the NIAID and the NIA plan to fund approximately four P01 awards. Applications may not request more than four percent annual inflationary increases for future years. Applications may not request budgets in excess of $750,000 total costs (direct and indirect) in the first year. An application with a first year requested amount in excess of the above will require written approval by senior NIAID and NIA officials via the program officers for acceptance of the application for processing. The usual PHS policies governing grants administration and management will apply. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NIAID and the NIA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background The most effective procedure for managing human infectious diseases is preventive immunization (vaccination). Despite the remarkable successes of vaccination in eradicating smallpox and soon, poliomyelitis, and preventing illness and death of many millions of children, there remain many infectious diseases that have not yielded to vigorous attempts to develop vaccines. Furthermore, it is increasingly evident that successful vaccination of elderly humans is a special problem that needs to be addressed due to the declining competence of the immune system with age. The generation of protective immunity depends upon a responsive immune system. During the last 10 years, there has been a flood of new information in the field of immunology. Much has been learned about the mechanisms of defined, protein antigen processing and presentation of key epitopes in a manner that engenders effective immune responses. Yet, very little is known about the antigens of pathogenic microorganisms and how they could be presented to drive desired types of immune responses. Similarly, a great deal is known about subsets of T lymphocytes and the spectrum of cytokines each subset produces, as well as about B lymphocytes and their responses to cytokines. Yet, relatively little is known about the characteristics and generation of memory T and B cells which are essential for long-lasting protective immunity. Moreover, the mechanisms responsible for the generation of cytotoxic T cells that are efficient in attacking and neutralizing cells in the body that are infected with viruses, bacteria and protozoa remain uncertain. Research Objectives and Scope The goal of this initiative is to further increase knowledge about the basic structures and functions of the immune system that lead to protective immunization against infectious diseases. HIV infection and its sequelae are not within the scope of this RFA. Examples of relevant research topics are provided below. However, the list of examples is neither complete nor restrictive: o Elucidation of the events and factors that lead to selective expression/expansion of morphologically and/or functionally distinguishable T cell subsets; o Studies on the phenotypic and functional stability of T cell subsets and control of the selective expression of cytokine genes by subsets of T cells; o The morphological and/or functional characteristics of memory B and T cells and clarification of mechanisms for generating specific memory cells; o Analysis of the roles played by different types and functional states of antigen processing/presenting cells and the cytokines they secrete in determining the major type of immune response, the effector mechanism expressed and/or isotypes of antibodies produced; and o Studies on the basic mechanisms that are affected by immunological adjuvants and examination of the immuno-enhancing properties of adjuvants All of the preceding examples represent central features of immune responses to antigens in general. However, they are particularly important, at present, in devising new approaches to vaccination against infectious, pathogenic organisms. Applications submitted in response to this RFA should focus on elucidating basic mechanisms that qualitatively and/or quantitatively enhance immune responses, both humoral and cell-mediated. Improved understanding of approaches to enhancing immune responses will be important not only to immunization of healthy, young adults but the elderly as well. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by April 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Program Director, the number and title of this RFA, and a list of the key investigators and their institution(s). Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 9/91). These application forms may be obtained from the institution's office for sponsored research or its equivalent and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 710-0267. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "BASIC BIOLOGY OF IMMUNE RESPONSES FOR VACCINE RESEARCH" must be typed in. In preparing the application in response to this RFA, the applicant should bear in mind the research objectives of this RFA. P01 applications should be prepared using the guidance and instructions provided in the NIAID Information Brochure on Program Project Grants and Multiproject Cooperative Agreements, available from the program staff listed under INQUIRIES. Failure to follow these instructions may result in delays in the review or in an incomplete application. It is highly recommended that the program staff listed under INQUIRIES be contacted in the early stages of preparing the application. Applications must be received by July 13, 1994. Applications that do not conform to the instructions contained in PHS 398 (rev. 9/91) application kit, will be judged non-responsive and will be returned to the applicant. The RFA label available in PHS 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. Applications received after the receipt date will be returned without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892 At the time of submission, two additional exact copies of the grant application and all five sets of the appendix must also be sent to dr. Mark Rohrbaugh at the address listed under INQUIRIES. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and for responsiveness by NIAID staff; those judged to be incomplete will be returned to the applicant without review. Those considered to be non-responsive may be returned without review. Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group to determine their scientific merit relative to other applications received in response to this RFA. The NIAID and the NIA will withdraw from competition those applications judged to be non-competitive for award and will notify the applicant and institutional business officials. Those applications judged by the reviewers to be competitive for award will be reviewed for scientific and technical merit by a review committee convened by the Division of Extramural Activities, NIAID. The second level of review will be provided by the Advisory Councils of the NIAID and the NIA. The factors to be considered in the evaluation of scientific merit of each application will be those used in the review of traditional research project grant applications, including: the novelty, originality, and feasibility of the approach; the training, experience, and research competence of the investigators; the adequacy of the experimental design; and the adequacy and suitability of the facilities. For program project applications, additional review criteria are used, which are outlined in the NIAID Information Brochure on Program Project Grants and Multiproject Cooperative Agreements. While the following review factors do not usually influence the priority score, they are nonetheless carefully considered by the initial review group: the appropriateness of the requested budget to the work proposed; the adequacy of protection of human subjects and/or animals in research; and the adherence to NIH guidelines concerning adequate representation of women and minorities in clinical research. Any documented concerns expressed by the initial review group about any of these factors on a given application may influence the recommendation of the Advisory Council concerning funding of that application. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program needs and balance, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: M. Michele Hogan, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7551 FAX: (301) 402-2571 Anna M. McCormick, Ph.D. Biology of Aging Program National Institute on Aging Gateway Building, Suite 2C231 Bethesda, MD 20892 Telephone: (301) 496-6402 FAX: (301) 402-0010 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and the five sets of appendices to: Mark Rohrbaugh, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8424 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: July 13, 1994 Scientific Review Date: October 1994 Advisory Council Date: February 1995 Earliest Award Date: April 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research and No. 93.866 - Aging Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. .
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files. |