PA-01-055: NEW TECHNOLOGIES FOR HIV AND HIV VACCINE RELATED RESEARCH

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.

This Program Announcement expires on March 1, 2004, unless reissued. NEW TECHNOLOGIES FOR HIV AND HIV VACCINE RELATED RESEARCH Release Date: February 22, 2001 PA NUMBER: PA-01-055 (see Notice of Inactivation NOT-AI-04-009) National Institute of Allergy and Infectious Diseases (http://www.niaid.nih.gov/) National Institute of Dental and Craniofacial Research (http://www.nidcr.nih.gov) Application Receipt Date: STANDARD AIDS RECEIPT DATES THIS PA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS PA. PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), invites applications to conduct novel and innovative research in three target areas: 1) development of improved technologies for detecting HIV, 2) utilization of novel technologies to evaluate immune responses to HIV vaccines, as well as expansion of the range and scope of immune functions currently measured in HIV vaccine trials, and 3) utilization of novel technologies to measure and correlate immune responses that are responsible for/associated with the efficacy of non-HIV licensed vaccines. This program announcement (PA) is an expansion of a previously advertised PA entitled Laboratory Methods to Assess Responses to HIV Vaccine Candidates (PA-99-044). This PA intends to complement the work conducted by the HIV Vaccine Trials Network (HVTN) and other programs supporting vaccine trials, as well as those conducting studies of animals receiving experimental HIV/SIV vaccines in prophylactic and/or therapeutic trials funded through programs in NIAID. 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 Program Announcement (PA), New Technologies for HIV and HIV Vaccine Related Research is related to the focus area of Immunization and Infectious Diseases. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, 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. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. MECHANISM OF SUPPORT This PA will use the National Institutes of Health (NIH) research project grant (R01, R03) award mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for an application submitted in response to this PA may not exceed five years. Specific application instructions have been modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. Complete and detailed instructions and information on Modular Grant applications can be found at http://grants.nih.gov/grants/funding/modular/modular.htm. A notice of modification and update (OD-00-046) regarding modular grants was released on 7/24/00 and can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-046.html. RESEARCH OBJECTIVES This PA will support the use of novel and innovative technologies to: 1) detect HIV, 2) quantitate and optimize measurement of immune responses to HIV and to candidate HIV vaccines, and 3) evaluate and quantitate immune responses responsible for the efficacy of licensed vaccines for other infectious diseases. The ultimate objectives of this PA are first, to assist the development of sensitive, standardized assays for use in clinical HIV vaccine studies and second, to obtain a clearer understanding of the correlates of protection from HIV infection and immune-mediated control of disease progression so as to facilitate vaccine design. Specifically, the PA encourages the development of new, highly sensitive technologies to permit the early recognition of HIV infection, and the detection of minimal levels of HIV replication and the differentiation from a transient infection that might arise in vaccinated individuals. Current laboratory assays, such as neutralization, cytotoxic T cell assays, and proliferation assays, measure established immune responses in HIV-infected or vaccinated individuals. However, there is no definitive evidence that these immune parameters are protective with regard to HIV infection or disease progression. Hence, the PA also encourages the development of novel assays to determine the mechanism(s) of action of candidate HIV vaccines, and to identify and measure the responses that may correlate with vaccine-induced protection in a systematic, standardized way. The PA will also support the measurement of immune responses that are responsible for the efficacy of other licensed vaccines as a yardstick by which to evaluate the type of assays required for performing HIV vaccine trials and for quantitating the relevant immune responses. A particular goal of this PA is to include the application of genome- wide expression profiling (chip, microarray or Serial Analysis of Gene Expression [SAGE]) technologies to clinical research studies of vaccine design, development, and evaluation, in any of the three targeted areas. It is known that the susceptibility to acute infection with many pathogens is influenced by the host’s genetic background. For example, in HIV infection, individuals lacking CCR5 surface expression are highly resistant to viral infection. Genetic variation that may influence host-pathogen interactions has implications for understanding human immune cell function, designing rationale preventive vaccines, and for predicting vaccine efficacy in population-based studies. In addition, oligonucleotide/cDNA arrays may allow comprehensive high- throughput screening of the effects of HIV infection or immunization (genetic, physiologic, pathologic, etc.) on gene expression in tissues and specific cell populations of interest. Additionally, it is not known to what extent the viral vaccine strain genotype/phenotype must match circulating viruses in order to afford protection. Techniques that allow rapid/thorough characterization of isolates in break-through infections would expedite an understanding of this issue. Research projects responsive to this PA may include comparative analyses of samples acquired from individuals infected with HIV, or who have been exposed to, but not infected with HIV. Studies in animals, particularly primates that have received SIV/SHIV vaccines are also encouraged. The measurement and correlation of vaccine-induced protective responses in individuals immunized with licensed vaccines such as Hepatitis B for the determination of the relevance and importance of establishing similar assays for HIV vaccine studies is also encouraged. Applications are encouraged to develop reagents (including non-clade B-based materials), to optimize or validate existing assays, or to adapt current assays such that they are simple, sensitive and easily transferable to international locations where future efficacy trials will be conducted. The PA will not directly support the conduct of human trials or animal vaccine studies. Scientific areas considered responsive to this PA may include, but are not limited to: o the development of novel, highly sensitive technologies to identify, characterize and quantitate HIV in blood and tissues , including lymphoid and oral tissues, saliva and gingival fluid. o the identification of new genetic or immune markers for immune responses to HIV, and exploration of their potential ability to serve as surrogates for protection from infection, disease progression or transmission to others o the comparison of candidate HIV vaccines to proven, efficacious, licensed, vaccines against other infectious diseases according to key immune parameters (e.g. kinetics, longevity, breadth of responses) using state-of-the art assays, such as ELISPOT o the development of assays to evaluate the magnitude and breadth of HIV-specific CD4 cell responses induced by vaccines that may be associated with improved prognosis in infected individuals o the development of laboratory assays that mimic the "in vivo" interaction between HIV-specific helper T cells and CTLs or B cells o the development or optimization of existing assays to evaluate and validate the magnitude and potential function of HIV-specific immune response (mucosal, systemic cellular, humoral) to HIV vaccine candidates in humans or experimental animals o the development of tissue culture assays to identify and quantify HIV antigen-specific primed B cells and distinguish effector cells from the memory pool o the development of innovative uses of DNA genome technology applicable to HIV clinical vaccine studies (e.g. HLA typing, subtyping the HIV genome, monitoring host gene expression in cell types or tissues post-infection or immunization) The research studies may be conducted within a single laboratory or in conjunction with other laboratories at the same or different institutions specializing in different research areas. Human specimens to be used in these studies should be collected under appropriate informed consent processes. Applicants are strongly encouraged to establish collaborations with individuals or institutions having relevant expertise in the ethical issues involving the use of fresh and stored human biological materials for research. Investigators should, prior to application, arrange for access to samples from existing clinical and cohort studies, such as those conducted by the HVTN or Prevention Trials network (PTN), through the existing "Material Transfer Agreements" of these organizations. It is the responsibility of the applicant to establish and fully document any collaborative arrangements with such networks or with other collaborators prior to the submission of a grant application. Potential applicants are encouraged to contact the program staff listed under INQUIRIES for guidance concerning the organization and scope of the proposed research and the preparation of the application. Program staff may be able to facilitate contact with appropriate HVTN or PTN investigators, as well as investigators performing DAIDS-supported preclinical studies in experimental animals. Program staff also may assist by suggesting reagent resources as well as by coordinating the comparative testing and validation of immunological assays by supplying appropriate samples from DAIDS-sponsored clinical networks. SPECIAL REQUIREMENTS Awardees will be invited to attend a meeting to present the progress of the work funded under this PA. Details of this meeting will be provided post-award. Thus, applicants should include in their overall budget request, funds for the PI to attend one two-day meeting per year in the Washington, D.C. area. TERMS AND CONDITIONS OF AWARD When clinical studies or trials are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. Terms and Conditions of Award will be included with awards. NIAID policy was announced in the NIH Guide on February 24, 2000 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-00-003.html. The full policy including terms and conditions of award is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf 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 subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is 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 UPDATED "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html), a complete copy of the updated Guidelines are available at: http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm. The revisions relate to NIH-defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to 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) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. 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 is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators may also obtain copies of these policies from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. 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. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 4/98) and will be accepted at the standard application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: GrantsInfo@nih.gov. In addition, the application kits can be found on the following URL: http://grants.nih.gov/grants/forms.htm. Applicants planning to submit an investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended/revised version of the preceding grant application types requesting $500,000 or more in direct costs for any year are advised that he or she must contact the Institute or Center (IC) program staff before submitting the application, i.e., as plans for the study are being developed. Furthermore, the application must obtain agreement from the IC staff that the IC will accept the application for consideration for award. Finally, the applicant must identify, in a cover letter sent with the application, the staff member and Institute or Center who agreed to accept assignment of the application. This policy requires an applicant to obtain agreement for acceptance of both any such application and any such subsequent amendment. Refer to the NIH Guide for Grants and Contracts, March 20, 1998 at http://grants.nih.gov/grants/guide/notice-files/not98-030.html SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS BUDGET INSTRUCTIONS Modular Grant applications will request direct costs in $25,000 modules, up to a total direct cost request of $250,000 per year. (Applications that request more than $250,000 direct costs in any year must follow the traditional PHS 398 application instructions.) The total direct costs must be requested in accordance with the program guidelines and the modifications made to the standard PHS 398 application instructions described below: PHS 398 o FACE PAGE: Items 7a and 7b should be completed, indicating Direct Costs (in $25,000 increments up to a maximum of $250,000) and Total Costs [Modular Total Direct plus Facilities and Administrative(F&A)costs] for the initial budget period Items 8a and 8b should be completed indicating the Direct and Total Costs for the entire proposed period of support. o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 of the PHS 398. It is not required and will not be accepted with the application. o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the categorical budget table on Form Page 5 of the PHS 398. It is not required and will not be accepted with the application. o BUDGET NARRATIVE JUSTIFICATION - Prepare a Modular Grant Budget Narrative page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for sample pages.) At the top of the page, enter the total direct costs requested for each year. This is not a Form page. Under Personnel, provide budget narrative for ALL personnel by position, role and level of effort. This includes consultants and any to be appointed positions. No individual salary information should be provided. However, the applicant should use the NIH appropriation language salary cap and the NIH policy for graduate student compensation in developing the budget request. For Consortium/Contractual costs, provide an estimate of total costs (direct plus facilities and administrative) for each year, each rounded to the nearest $1,000. List the individuals/ organizations with whom consortium or contractual arrangements have been made, the percent effort of all personnel, and the role on the project. Indicate whether the collaborating institution is foreign or domestic. The total cost for a consortium/contractual arrangement is included in the overall requested modular direct cost amount. Include a Letter of Commitment or Intent if there is or is to be a subcontract/ consortium. Provide an additional narrative budget justification for any variation in the number of modules requested. o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by reviewers in the assessment of each individual"s qualifications for a specific role in the proposed project, as well as to evaluate the overall qualifications of the research team. A biographical sketch is required for all key personnel, including consultants, following the instructions below. No more than three pages may be used for each person. A sample biographical sketch may be viewed at: http://grants.nih.gov/grants/funding/modular/modular.htm - Complete the educational block at the top of the form page - List position(s) and any honors - Provide information, including overall goals and responsibilities, on research projects ongoing or completed during the last three years - List selected peer-reviewed publications, with full citations o CHECKLIST - This page should be completed and submitted with the application. Applicant institutions should calculate the Facilities and Administration (F&A) costs using the current negotiated F&A rate, less exclusions, for the initial budget period and all future budget periods. It is not necessary to list the exclusions on the Checklist nor anywhere in the application. If the F&A rate agreement has been established, indicate the type of agreement and the date. All appropriate exclusions must be applied in the calculation of the F&A costs for the initial budget period and all future budget years. o The applicant should provide the name and phone number of the individual to contact concerning fiscal and administrative issues if additional information is necessary following the initial review. The title and number of the program announcement must be typed on line 2 of the face page of the application form and the YES box must be marked. Applications not received as a single package on the receipt date or not conforming to the instructions, including page limitations and font size, contained in PHS 398 Application Kit (rev. 4/98) will be judged non-responsive and will be returned to the applicant. Submit a signed, typewritten original of the application, including the Checklist, and five 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) REVIEW CONSIDERATIONS Applications will be assigned on the basis of established NIH referral guidelines. Applications will be evaluated for scientific and technical merit by an appropriate scientific review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. (1) Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? (2) Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? (3) Innovation: Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? (5) Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated o The reasonableness of the proposed budget and duration in relation to the proposed research o The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application Additional scientific/technical merit criteria specific to the objectives of the PA and the mechanism used must be included if they are to be used in the review. AWARD CRITERIA Applications will compete for available funds with all other recommended applications. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, and program priority. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Patricia D Souza, Ph.D. Vaccine Prevention and Research Program Division of AIDS National Institute of Allergy and Infectious Diseases Room 4152, MSC-7628 6700-B Rockledge Drive Bethesda, MD 20892-7628 Telephone: (301) 496-8379 FAX: (301) 402-3684 Email: PD6N@NIH.GOV Dennis F. Mangan, Ph.D. Chief, Infectious Diseases and Immunity Branch Division of Extramural Research, National Institute of Dental and Craniofacial Research Blg. 45, Room 4AN-32F Bethesda, MD 20892-6402 Phone: 301 594-2421 Fax: 301 480-8318 Email: Dennis.Mangan@nih.gov Direct inquiries regarding fiscal matters to: Ms. Jeannette Gordon Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 3222, MSC-7614 6700-B Rockledge Drive Bethesda, MD 20892-7614 Telephone: (301) 496-7075 FAX: (301) 480-3780 Email: jg82s@nih.gov Martin R. Rubinstein Division of Extramural Research National Institute of Dental Research Building 45, Room 4AN-44A Bethesda, MD 20892-6402 Telephone: (301) 594-4800 Fax: 301 480-8301 Email: Martin.Rubinstein@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, (Microbiology and Infectious Diseases Research) and No.93.121 (Oral Diseases and Disorders 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 PHS 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, and portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices