RFP No. NIH-NIAID-DAIDS-98-14 Title: "PRIMATE IMMUNOLOGY LABORATORY FOR AIDS VACCINE RESEARCH AND DEVELOPMENT" Issued by: Toni A. Kuhn Contracting Officer NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 DATE ISSUED: AUGUST 22, 1997 PROPOSAL DATE DUE: NOVEMBER 3, 1997 4:30 P.M. (EST) Ladies and Gentlemen: You are invited to submit a proposal in accordance with the requirements of this RFP (NIH-NIAID-DAIDS-98-14) entitled "PRIMATE IMMUNOLOGY LABORATORY FOR AIDS VACCINE RESEARCH AND DEVELOPMENT." The Government anticipates the award of ONE (1), FIVE (5) YEAR, cost-reimbursement, completion type contract as a result of this RFP. The documents included with this electronic STREAMLINED RFP package are as follows: - Introduction, Background and Work Statement, dated August 22, 1997 (Attachment A) - Deliverables and Reporting Requirements, dated August 22, 1997 (Attachment B) - Evaluation Factors for Award, dated August 22, 1997 (Attachment C) - Specific RFP Instructions and Provisions (Attachment D) - Applicable RFP References (Attachment E) In addition to the directory which you are currently in (i.e., the streamlined RFP), there are five (5) other SUBDIRECTORIES in the Gopher System (gopher://gopher.nih.gov/11/res/rd-rfp/rfpref.c) which must be retrieved, in whole or in part, in order to submit a proposal (the applicable portions are explained in Attachment E). The SUBDIRECTORIES are: STANDARD RFP INSTRUCTIONS AND PROVISIONS OPTIONAL RFP INSTRUCTIONS AND PROVISIONS FORMS, FORMATS AND ATTACHMENTS REPRESENTATIONS AND CERTIFICATIONS SAMPLE CONTRACT FORMAT-GENERAL If you are unable to download any of these documents, please contact Grace Bruce, Contract Specialist, by phone/fax/internet at the numbers/addresses listed below. The attachments/documents listed above represent all the necessary information required for the submission of a proposal for this acquisition. Following proposal submission and review, additional information will be requested by the Contracting Officer from all offerors which comprise the COMPETITIVE RANGE. The BUSINESS and TECHNICAL proposals must be separate from one another in the proposal package as the peer review panel will only receive the technical proposal. The BUSINESS PROPOSAL must be signed by an authorized official of your organization, and must contain a detailed breakdown of costs by year, for each cost category/element; the BASIS for all costs must be explained, but supporting documentation need NOT be submitted with the proposal (COST AND PRICING DOCUMENTAION WILL BE REQUESTED AFTER THE COMPETITIVE RANGE IS ESTABLISHED). See Standard RFP Instructions and Provisions, in the Gopher System (gopher://gopher.nih.gov/11/res/rd-rfp/rfpref.c), for more detail on the BUSINESS PROPOSAL requirements. With the Business Proposal, please submit Form NIH-2043, "Proposal Summary and Data Record," contained in the NIH Gopher System (gopher://gopher.nih.gov/11/res/rd-rfp/rfpref.c) under the FORMS, FORMATS, AND ATTACHMENTS. Note that in addition to telephone and fax numbers, the INTERNET addresses of both the Principal Investigator and the responsible business representative are to be included on the form. DUE TO THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES CURRENT BUDGET RESTRICTIONS, IT IS RECOMMENDED THAT ANY PROPOSED ANNUAL INCREASE IN COSTS FOR INFLATION BE LIMITED TO NO MORE THAN 3% OF TOTAL COSTS PER YEAR. FINAL INFLATION INCREASES WILL BE SUBJECT TO THE NEGOTIATION PROCESS TAKING INTO CONSIDERATION THE MOST CURRENT CONSUMER PRICE INDEX (CPI). You are reminded that the "Technical Proposal cover Sheet" must be completed in full detail and used as the cover sheet for each copy of your technical proposal. A copy of this form is contained in the NIH Gopher System (gopher://gopher.nih.gov/11/res/rd-rfp/rfpref.c) under the FORMS, FORMATS, AND ATTACHMENTS. It is important that you list all professional personnel and organizations named in the proposal who have any role in the proposed work, including: staff of the primary organization(offeror), subcontractors, collaborating organizations, and consultants. Organizational affiliation(s) must be indicated for every person named. You may use additional sheets, as needed, following the format shown in the Technical Proposal Cover Sheet. This information will be used to ensure that there will be no conflict of interest when selecting review committee members. Your attention is further directed to the "Proposal Intent" form contained in Attachment D, item 9. Please complete this form and return it to this office on or before OCTOBER 14, 1997. This will allow us to expedite preparations for the peer review of proposals. If you intend to submit a proposal in response to this RFP, IT IS ESSENTIAL THAT YOU IMMEDIATELY NOTIFY MS. GRACE BRUCE, CONTRACT SPECIALIST, OF THE NIAID CONTRACTING OFFICE AT THE FOLLOWING INTERNET ADDRESS: gb15w@nih.gov IF YOU FAIL TO NOTIFY THE CONTRACTING OFFICE OF YOUR INTEREST, YOU WILL NOT RECEIVE NOTIFICATION OF AMENDMENTS ISSUED TO THE RFP. HOWEVER, ALL AMENDMENTS WILL BE POSTED ON THE NIH GOPHER AND THE NIH HOME PAGE. Funds are NOT presently available for this requirement. The Government's obligation under a resulting contract is contingent upon availability of appropriated funds from which payment for contract purposes can be made. The original and twenty-four (24) copies of your technical proposal and the original and four (4) copies of your business proposal must be received NO LATER THAN NOVEMBER 3, 1997, AT 4:30 p.m. LOCAL TIME AT THE ADDRESSES LISTED IN ATTACHMENT D, ITEM 4. Questions concerning any areas of uncertainty which in your opinion require clarification or correction, must be furnished in writing to Ms. Grace Bruce no later than SEPTEMBER 30, 1997, at the Contract Specialist address located in Attachment D, item 4. The questions should be marked "Offeror's Questions, RFP-NIH-NIAID-DAIDS-98-14" (Fax or e-mail communication is preferred). If you have any additional questions regarding this RFP, please contact Ms. Grace Bruce at the internet electronic mail address: gb15w@nih.gov or by phone at 301/496-0195, or by fax at 301/402-0972. Collect calls will NOT be accepted. Sincerely, /s/ Toni A. Kuhn Chief, AIDS Preclinical Research Contract Section Contract Management Branch National Institute of Allergy and Infectious Diseases Attachments: A - E ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DAIDS-98-14 STREAMLINED RFP --------------- ATTACHMENT A RFP SECTION C INTRODUCTION, BACKGROUND AND WORK STATEMENT (August 22, 1997) INTRODUCTION ------------ The objective of this contract is to continue to provide a centralized laboratory for standardized and comparative assessment of immunological responses induced in primates by immunization with prototype HIV and/or SIV vaccines. The demonstration of protection by SIV and HIV vaccines in primates has led to cautious optimism for development of a protective vaccine against AIDS. To translate the findings from primates to an effective HIV vaccine in humans, it is essential to understand which immune responses provide protection and against which antigen(s) immunity is directed. However, assessment of immune responses in primates is difficult and requires expertise generally not available at primate centers, where the best animal resources are located. Standard protocols for assessment of cell-mediated immune responses are still being developed. Analysis of virus neutralization with stocks used for animal challenge is difficult and assays vary among laboratories. Analysis of mucosal immune responses in primates is still in the developmental stage. Furthermore, these assessments are time-consuming and labor-intensive. Focusing resources in centralized sites provides the necessary data to compare the immune responses different vaccines can produce and to correlate them with protection. The current contractor for the Primate Immunology Laboratory, Beth Israel Hospital (N01-AI-35166), evaluates the cellular immune responses of immunized and infected macaques, with emphasis on CTL assays. Duke University, as a subcontractor, conducts assays to assess the level and breadth of virus neutralizing antibodies generated by immunizations. The Laboratory has developed sensitive CTL assays in the rhesus macaque system, using antigen-specific stimulation of effector cells, and has demonstrated the presence of CD8+ CTLs in monkeys immunized with DNA vaccines and with some recombinant vector vaccines. Epitopes in the HIV envelope recognized by the monkeys have been identified and sequenced. Neutralizing antibody assays against a variety of SIVs, SHIVs, and HIVs have been developed, and the presence of neutralizing antibodies against the challenge virus has been correlated with protection from infection in several of the SHIV challenges of animals immunized with HIV envelope vaccines. The new Primate Immunology Laboratory contractor will continue to test humoral and cellular immune responses, and will, additionally, evaluate the mucosal immune responses of macaques and other primates vaccinated with various candidate SIV or HIV vaccines. It will continue to support studies conducted at NIAID's Simian Vaccine Evaluation Units (SVEUs), which have over 200 primates in a variety of vaccine studies. [SVEU contractors are: Advanced BioScience Laboratories (NO1-AI-65314), Henry M. Jackson Foundation (NO1-AI- 65301), TSI Mason Laboratories (NO1-AI-65303), Tulane University (NO1- AI-65300), and University of Washington (NO1-AI-65302)]. The Laboratory will develop and employ assays that are more labor- intensive and/or complex than those currently undertaken by the SVEUs. These assays would include, among others, type-specific and cross- reactive neutralizing and enhancing antibody levels, antibody- dependent cell cytotoxicity, assays of cell-mediated immunity, such as T-cell proliferative responses to viral proteins or peptides, and cytotoxic T cell reactions, including characterization of MHC restriction, as well as assessment of the activity of anti-viral, suppressor factors. The Laboratory will also conduct assays to measure antibody responses, and perhaps eventually cellular immune responses, at mucosal surfaces of immunized and infected primates. The current Primate Immunology Laboratory contract was awarded to Beth Israel Hospital in 1994 and was scaled to provide support sufficient for three SVEUs. As a result of the FY96 recompetition of the SVEUs, five units were awarded. In addition, a small contract supported through an interagency agreement with the National Cancer Institute provides additional capacity for the conduct of neutralizing antibody assays, and Master Agreement Orders (funded through NIAID's Master Agreement Program supported by the Preclinical Research Branch) provide CTL assays and virus neutralization assays for several vaccine studies being conducted at non-SVEU contract sites. This RFP Work Statement and guidance for preparation of cost proposals reflects these increased requirements. WORK STATEMENT PRIMATE IMMUNOLOGY LABORATORY FOR AIDS VACCINE RESEARCH AND DEVELOPMENT Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the Government under the terms of this contract, as needed to provide a Primate Immunology Laboratory that shall support the evaluation of prototype AIDS vaccines in primates at several institutions under the sponsorship of the Division of AIDS, NIAID, NIH. Specifically, the Contractor shall: A. Evaluate and characterize the cellular immune responses of nonhuman primates that have been immunized with HIV or SIV vaccines or infected with SHIV or SIV. Assays to be conducted shall include, but not be limited to, those described below: 1. Perform assays to detect HIV or SIV antigen-specific cytotoxic T lymphocytes (CTLs) in nonhuman primates immunized with HIV or SIV vaccines. [NOTE #1 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to conduct 1000 CTL assays per year (for 150 monkeys). Offerors should assume that they will mainly conduct assays to detect HIV and SIV env-specific and gag-specific CTLs, but that they will be requested, less frequently, to conduct assays to detect CTLs directed at other viral targets, such as pol and nef] a. Receive/obtain peripheral blood cells from all the animals in a vaccine study being conducted at a SVEU site or by other investigators, and establish transformed B lymphoblastoid cell lines to use as stimulator cells and/or target cells in CTL assays. Freeze a stock of each transformed cell line and maintain the transformed B cell lines for use in the CTL assays. [NOTE #2 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to establish and maintain transformed B cell lines for 150 monkeys each year.] b. Perform SIV or HIV antigen-specific (as appropriate for the vaccine study) in vitro stimulation and expansion of SIV or HIV specific CTL precursors from immunized animals and, if required by the study protocol, infected animals. c. Perform assays to detect CTL activity directed against SIV or HIV epitopes (as appropriate to the specific study) in immunized nonhuman primates, and in nonhuman primates after virus challenge (if required by the individual protocol), using recombinant virus- infected, peptide pulsed, or other appropriate autologous cell targets; include appropriate controls in the assays. d. Characterize SIV or HIV antigen-specific CTL activity that is detected. Studies to be conducted at the request of the Project Officer may include: (1) determination whether the CTL effector cells are CD8+ cells or CD4+ cells, (2) exclusion of NK (natural killer) and ADCC (antibody- dependent complement-mediated cytotoxicity) activity, (3) determination that the CTL activity is MHC restricted, (4) determination of the CTL precursor frequency by limiting dilution analysis, and (5) generation of T cell clones with anti-HIV or SIV cytotoxic activity. [NOTE #3 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should assume that they will be requested to further characterize the CTL activity of 50 samples per year.] 2. Perform in vitro assays to evaluate the ability of CD8+ lymphocytes from immunized nonhuman primates to reduce or inhibit HIV or SHIV virus replication in either autologous CD4 lymphocytes from the animals in the vaccine studies, or appropriate heterologous target lymphocytes; include appropriate controls. [NOTE #4 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to conduct 300 of these CD8 suppressor assays per year.] B. Perform assays to evaluate and characterize the humoral immune responses of animals that have been immunized with HIV or SIV vaccines or infected with SHIV or SIV. Assays to be conducted are to include, but not be limited to, the following, and are to include appropriate controls: 1. For animals that have been immunized with HIV vaccines or infected with SHIV: a. Perform ELISA, western blot or other appropriate assays to detect the presence of HIV or SIV antibodies. b. Perform assays to determine the ability of sera (or mucosal secretions as assays are developed) from animals immunized with HIV vaccines, or of sera from infected nonhuman primates after SHIV challenge, to neutralize infection of cell lines and/or primary cells (PBMC) by the HIV strain used for the vaccine. Determine the ability of the sera to neutralize the SHIV made with the envelope gene of the homologous (vaccine) HIV, if the appropriate SHIV virus stock is available. Characterize the antibodies, including determining the neutralization titer against the vaccine (homologous) HIV or SHIV strain. [NOTE #5 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to conduct 1000 SHIV neutralization assays per year and 200 HIV neutralization assays per year, using sera from immunized monkeys.] c. Determine the neutralization titer against infection of appropriate cell lines and/or PBMC by heterologous laboratory strains of HIV or heterologous SHIVs for sera (or mucosal secretions) that were determined (above) to neutralize the homologous strain of HIV or the SHIV containing the envelope gene of the homologous HIV. [NOTE #6 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to conduct 200 assays to determine the ability of the monkey sera to neutralize heterologous HIV strains and 200 assays to determine the ability of the monkey sera to neutralize heterologous SHIV strains per year.] d. Determine the ability to neutralize infection of appropriate cell lines and/or primary PBMC and/or primary macrophages by primary, "field" isolates of HIV grown only in primary cells for sera (or mucosal secretions) that show the ability to neutralize heterologous HIV isolates (above). [NOTE #7 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to conduct 100 assays to determine the ability of the monkey sera to neutralize primary HIV isolates per year.] 2. For animals that have been immunized with SIV vaccines or infected with SIV: a. Determine the capability of sera (or mucosal secretions) from animals immunized with SIV vaccines, or infected with SIV, to neutralize infection of cell lines and/or primary cells (PBMC) by the SIV strain used for the vaccine. Further characterize these antibodies, including determining the neutralization titer against the vaccine (homologous) SIV strain. [NOTE #8 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to conduct 1000 SIV neutralization assays per year, assessing sera from immunized monkeys.] b. Determine the neutralization titer against infection of appropriate cell lines and/or PBMC by a heterologous strain or strains of SIV for sera (or mucosal secretions) that were determined (above) to neutralize the homologous strain of SIV. [NOTE #9 TO OFFERORS: For purposes of preparing a cost proposal, Offerors should propose to conduct 200 assays per year to determine the ability of the monkey sera to neutralize a heterologous SIV strain.] 3. Grow appropriate HIV, SHIV, and SIV virus stocks, determine the in vitro titer of the stocks, and demonstrate that the viruses are able to be neutralized by sera from HIV-infected people or SHIV- or SIV-infected monkeys prior to conducting neutralization assays with the sera from the vaccine studies. Virus stocks to be prepared shall be selected with the approval of the Project Officer. [NOTE #10 TO OFFERORS: The SHIV, HIV or SIV strain to be used in the neutralization assays will be determined by the strain used in the vaccine and the strain(s) selected for heterologous challenge. For purposes of preparing a cost proposal, Offerors should assume that stocks of HIV-1IIIB, HIV-1MN, one "primary" HIV isolate, stocks of three SHIVs (such as SHIVIIIB, SHIVSF2,SHIV-Mn, or SHIV-89.6), and stocks of three SIVs (such as SIVmac, SIVmne, SIV-DeltaB670) will be made and titered for the in vitro neutralization assays.] C. Perform assays to evaluate and characterize immune responses at mucosal sites in nonhuman primates that have been immunized with HIV or SIV vaccines or infected with SHIV or SIV. 1. Perform assays to detect and measure HIV-specific or SIV- specific antibodies (IgG, IgA, and secretory IgA antibodies) or antibody-secreting cells in mucosal secretions such as vaginal and rectal swabs/washes and saliva of immunized or infected macaques. Include assays on appropriate negative and positive control samples. 2. Conduct assays to evaluate functional humoral immune responses (such as virus neutralization assays as described in section 3 above) or functional cellular immune responses (such as CTL responses as described in section 1 above) in mucosal secretions or mucosal tissues of immunized or infected macaques, as appropriate assays are developed or become available. D. Develop new or more sensitive assays to detect and evaluate humoral and cellular immune responses in immunized animals (including, for example, assays to detect T lymphocytes that specifically bind peptide-MHC Class I complexes, assays to detect nonhuman primate cytokine/chemokine expression, and assays to detect mucosal immune responses) in order to maintain the capability of providing state-of-the-art assays under this contract. Improve current assays (as needed). [NOTE #11 TO OFFERORS: For purposes of preparing a cost proposal, Offerors are requested to discuss their experience in improving existing and developing new immunological assays, but no additional budgetary provisions are necessary.] E. Receive, catalog, track, and maintain an inventory of the specimens that arrive for evaluation: 1. Advise sample suppliers of the most suitable manner for shipment of sera, whole blood, cells or other specimens for evaluation and arrange for the transfer of these specimens from primate laboratories to the Contractor. All shipments shall be coordinated so that activity/viability of specimens are not be adversely affected. 2. Pick up or arrange for pick up of incoming specimen shipments from a specified airport or other contact site in a timely manner and assure maintenance of activity and/or viability of the specimens by providing the appropriate temperature in transit from the airport or other contact site to the Contractor's laboratory. 3. Receive and catalog specimens arriving for evaluation from the primate laboratories. Maintain documentation on file for all incoming specimens, including but not limited to: primate subject identification number, trial site, protocol identification number, specimen collection date and condition of sample upon arrival. 4. Store cataloged, aliquotted specimens under appropriate conditions to retain maximum immunological and biological activity. 5. Maintain specimen tracking and inventory system such that specimens can be traced and located from receipt through processing and assay analysis. F. Manage and report study data: 1. Compile and maintain a computerized database of all assay results. Results are to be recorded with designations of type of assay, virus and cell type used, study protocol number, animal number, specimen collection date, and other information requested by the Project Officer. 2. Designate a project coordinator to manage the day-to-day conduct of the study, to interact with the SVEU laboratories or other laboratories providing non-human primate samples from the vaccine study or studies, and to provide information on the status of the assay results to the Project Officer. 3. Report data and results to NIAID or to a designated NIAID contractor. Printouts of data and verbal reports of the status of the study are to be provided on an ongoing basis during the course of the study at the request of the Project Officer, in addition to the required periodic (quarterly and final) written reports describing the progress of the study. Data shall be reported in a format approved by the Project Officer. 4. Meet with Project Officer and attend Scientific Meetings: Attend meetings (three per year) with the Project Officer and other staff of the Preclinical Research Branch, VPRP, DAIDS, NIAID. [NOTE #12 TO OFFEROR: For purposes of preparing a cost proposal, assume 3 trips a year for the Principal Investigator (or designate) and the Co-investigator (or designate) to attend the meetings with the Project Officer which will be held in the Washington, D.C. metropolitan area. One of these meetings will be at the Annual National Cooperative Vaccine Development Group Meeting and will include representatives from the SIV VEUs. The other meetings will be held in Bethesda/Rockville. In addition, for purposes of preparing a cost proposal, Offerors should include a travel budget for the Principal Investigator and the Co-Investigator each to attend one Scientific Meeting a year to present results obtained under this contract.] 5. Obtain clearance for publication. Provide advance copies of draft manuscripts (including abstracts and public presentations) resulting from this contract to the Project Officer and obtain clearance in writing before submitting for publication or presentation. The Contractor shall be bound by the same terms as the Government to respect the confidential nature of information provided by the preclinical trial investigators and the vaccine product developers. Support from the Government contract shall be acknowledged in all abstracts, presentations, and publications. [NOTE #13 TO OFFEROR: An Advance Understanding (See article XX) will be inserted in any resultant contract, stating that the Contractor agrees that manuscripts based on data generated under this contract will not be submitted for publication or presentation until written concurrence has been received from the Project Officer.] G. Provide facilities and resources 1. Provide facilities and equipment for the work to be conducted, including a biosafety level 2 or 3 laboratory for conducting work with live HIV and SHIV as well as samples from infected monkeys. 2. Provide, maintain, and operate facilities for controlled storage of virus stocks, cell stocks, and other samples and reagents, including storage at -10 to -20 degrees C, at -70 to - 90 degrees C, and in liquid nitrogen, with appropriate monitoring of storage conditions to guarantee continuous proper storage. The reliability of supply systems, electrical power, and backup support systems shall be ensured by the contractor. 3. Provide protective garments, equipment and sufficient monitoring to assure safe handling of potentially hazardous materials, including radioactive materials. Specifically, the contractor shall comply with all applicable health and safety regulations while conducting the work set forth herein. H. Ensure an orderly transition to a successor Contractor. By the end of the fourth year of this contract, the Contractor shall refine a plan for and be prepared to implement an orderly transition of data and specimens to a successor Contractor or to the Government, subject to Project Officer approval, and shall deliver, if requested by the Project Officer and by the completion date of the Contract, the following items: Original data, reagents, stored specimens, and any necessary information related thereto, and Government owned equipment and property. ******************************************************************** ******************************************************************** RFP-NIH-NIAID-DAIDS-98-14 ATTACHMENT B DELIVERABLES AND REPORTING REQUIREMENTS (August 22, 1997) I. Quarterly Progress Reports By the fifteenth working day of the month following the end of each quarter, for the first three quarters of the year, the Contractor shall submit three (3) copies of a quarterly progress report as described below. Two (2) copies should be submitted to the Project Officer and one (1) copy to the Contracting Officer. The quarterly report should be factual and concise and consist of the following: 1) A title page containing: (a) Contract number and title (b) Sequence of report; e.g., "Year 1, 2nd Quarterly Report" (c) Period of performance being reported (d) Contractor's name and address (e) Date of submission 2) Reports shall include, but are not limited to the following information: (a) A brief introduction covering the objective and scope of the contract effort. (b) A description of overall progress plus short descriptions of the methodology and reagents employed for each immunological or virological assay employed during the performance period, specifying changes in critical reagents or protocols. (c) Separate tables listing: 1] An inventory of specimens received during the performance period, but on which assays have not yet been performed. 2] The assays performed during the performance period, indicating number of each performed. 3] The specimens on which assays were performed during the performance period. 4] An ordered listing and interpretation of results from all immunological assays performed during the performance period. (d) A description of any technical or performance problems encountered and corrective actions planned or taken. An explanation of any differences between planned and actual progress. (e) Selected other information as may be required by the Project Officer. 3) A quarterly report is not due when an annual report is due. II. Annual Report On or before the last day of the Contract year, the Contractor shall submit three (3) copies of an annual report. Two (2) copies shall be submitted to the Project Officer and one (1) copy shall be submitted to the Contracting Officer. The annual report shall summarize progress for the entire contract year, following the same format as for the quarterly reports, and shall take the place of the fourth quarterly report. In addition, it shall include abstracts, manuscripts in progress or submitted, and publications resulting from the performance of work under this contract. An annual report is not required when the final report is due. III.Final Report The contractor shall submit three (3) copies of the final report documents, two (2) copies to the Project Officer and one (1) copy to the Contracting Officer, which shall summarize the results of the entire contract work for the complete performance period. This report shall be in sufficient detail to explain comprehensively the results achieved and shall be submitted no later than the completion date of the Contract. The final report shall contain: 1) Title Page as described above in paragraph I. 1) (a). 2) Introduction covering the purpose and scope of the contract effort. 3) Description of the overall progress, plus a separate description of each protocol and type of assay employed and its modifications and performance on the contract during the period of performance. Descriptions shall include pertinent immunological assay data in tables or graphs as appropriate to present significant results achieved, conclusions resulting from analysis, and a scientific evaluation of the data accrued under the contract. 4) Copies of any abstracts, manuscripts, and publications. IV. Other Deliverables. The Contractor, subject to Project Officer approval shall deliver to the Government or its designee by the completion date of the contract, the following items: 1) Stored primate-derived specimens or reagents including those received by the Contractor from the Project Officer or designated investigators. 2) A computer-generated listing of accurate and updated information on the specimen inventory, including activities of the Contractor, computerized data files, original data and any necessary information related thereto; 3) Labeled and inventoried paper files; and 4) Government-owned equipment and property. V. If the Contractor becomes unable to deliver the reports or other deliverables here specified within the period of performance because of unforeseen difficulties, notwithstanding the exercise of good faith and diligent efforts in performance of the work, the Contractor shall give the Contracting Officer immediate written notice of anticipated delays with reasons therefore at the address given below in section VII. VI. Copies of the technical reports shall be submitted as follows: Type of No. of Report Copies Addresses: Quarterly 2 Project Officer PRB, VPRP, DAIDS Annual 2 NIAID, NIH Final 2 Solar Bldg., Rm. 2A33 6003 Executive Blvd., MSC 7620 Bethesda, MD 20892-7620 Quarterly 1 Contract Specialist Annual 1 CMB, DEA, NIAID, NIH Final 1 Solar Bldg., Rm. 3C07 6003 Executive Blvd., MSC 7610 Bethesda, MD 20892-7610 ******************************************************************** ******************************************************************** RFP-NIH-NIAID-DAIDS-98-14 ATTACHMENT C (August 22, 1997) EVALUATION FACTORS FOR AWARD RFP SECTION M ____________________________ 1. GENERAL Selection of an offeror for contract award will be based on an evaluation of proposals against two factors. The factors in order of importance are 1) technical and 2) cost. Although technical factors are of paramount consideration in the award of the contract, cost or price are also important to the overall contract award decision. All evaluation factors other than cost or price, when combined, are significantly more important than cost or price. Offerors are advised that award will be made to that offeror whose proposal provides the best overall value to the Government. The evaluation will be based on the demonstrated capabilities of the prospective contractors in relation to the needs of the project as set forth in the RFP. The merits of each proposal will be evaluated carefully. Each proposal must document the feasibility of successful implementation of the requirements of the RFP. Offerors must submit information sufficient to evaluate their proposals based on the detailed criteria listed below. Listed below are mandatory qualification criteria and technical evaluation criteria. The mandatory qualification criteria establishes conditions that MUST be met at the time of receipt of Best and Final Offers (BAFO) by the Contracting Officer in order for your proposal to be considered any further for award. The technical evaluation criteria are used by the technical evaluation committee when reviewing the technical proposals. The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes. Proposals will be judged solely on the written material provided by the Offerors. 2. MANDATORY QUALIFICATION CRITERIA The following mandatory qualification criteria establish conditions that MUST be met by the time of submission of the Best and Final Offer in order for the proposal to be considered for award: The Contractor must have available biosafety level 2 or 3 facilities of sufficient capacity for all laboratory procedures and assays employing HIV-1, SIV, or SHIV isolates. 3. TECHNICAL EVALUATION CRITERIA 1. PERSONNEL . . . . . . . . . . . . . . . . . . . Total: 60 points Documented experience, expertise, and availability of the Principal Investigator and other proposed professional and technical staff (including any consultants or subcontractors) necessary to perform the specified tasks, including experience in the conduct of large numbers of the specified assays for multiple collaborations: Experience in developing and conducting assays to detect and characterize HIV-specific or SIV-specific cellular immune responses in nonhuman primates that have been immunized with HIV or SIV vaccines or infected with SHIV or SIV, including the conduct of assays to detect cytotoxic T cell (CTL) activity directed against SIV or HIV proteins or peptides and CD8 suppressor cell activity that inhibits SIV, SHIV, or HIV replication in CD4+ lymphocytes. Experience in developing and conducting assays to detect and characterize the humoral immune responses of animals immunized with HIV or SIV vaccines or infected with SHIV or SIV, including the conduct of ELISA and western blot assays to detect the presence of HIV- or SIV-specific antibodies, and assays to detect and determine the titer of neutralizing antibodies directed against SHIV, HIV, or SIV. Experience in developing and conducting assays to detect and characterize immune responses at mucosal surfaces or in mucosal secretions of nonhuman primates immunized with HIV or SIV vaccines or infected with SHIV, SIV, or HIV. Experience of the Principal Investigator in the management, administration, and coordination of a comparable technical effort to the one being requested, i.e., a laboratory that has conducted a large number of assays in collaboration with multiple investigators. Relevant experience of person(s) designated to manage the computer databases. 2. TECHNICAL APPROACH/METHODOLOGY . . . . . . . Total: 30 points Appropriateness of the proposed technical approaches and methodologies to be used to conduct the specified tasks. Completeness of description of the proposed methodologies and thoroughness of discussion of potential problems and appropriate controls and alternate approaches to be used to conduct the proposed tasks: Detection and characterization of cellular immune responses of nonhuman primates that have been immunized with HIV or SIV vaccines or infected with SHIV or SIV, including assays to detect and characterize CTLs to SIV and/or HIV proteins or peptides and to assess CD8 suppressor cell activity in the immunized animals. Detection and characterization of humoral immune responses of animals that have been immunized with HIV or SIV vaccines or infected with SHIV or SIV, including assays such as ELISA and western blot assays to detect HIV- and SIV-specific antibodies, assays to detect neutralizing antibody activity directed against HIV (both "lab strains" and "primary strains"), SHIV, and SIV, and the preparation and characterization of HIV, SHIV, and SIV virus stocks for use in neutralization assays. Detection and characterization of immune responses at mucosal surfaces or in mucosal secretions of nonhuman primates immunized with HIV or SIV vaccines or infected with SHIV or SIV, including assays to detect HIV- and SIV-specific IgG, IgA, and proposed assays to detect HIV- and SIV- specific cellular immune responses. Acquisition, storage, and management of specimens received from vaccine studies for assays. Tabulation of assay results and maintenance of computer data base of data from assays. 3. RESOURCES AND FACILITIES . . . . . . . . . . . . Total: 10 points Documented availability of laboratory facilities, resources, and equipment necessary to conduct the specified tasks, including appropriate biocontainment laboratory facilities for conducting work with live, infectious SIV, SHIV, or HIV. Documented availability of adequate computer resources for data reporting. TOTAL:100 points ******************************************************************** ******************************************************************** RFP-NIH-NIAID-DAIDS-98-14 ATTACHMENT D SPECIFIC RFP INSTRUCTIONS AND PROVISIONS ---------------------------------------- NOTICE TO OFFERORS: This attachment contains proposal instructions and information which are specifically related to this acquisition. The information provided below is only a portion of the instructions and notices required for the submission of a proposal. References to additional, more general, information and forms regarding proposal preparation are contained in Attachment E, "Applicable RFP References." 1. SIC CODE AND SMALL BUSINESS SIZE STANDARD (NIH 3150) (JAN 1997) Note: The following information is to be used by the offeror in preparing its Representations and Certifications (See Attachment E, item 4 of this RFP), specifically in completing the provision entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS (JAN 1997), FAR 52.219-1: (a) The standard industrial classification (SIC) code for this acquisition is 8733. (b) (1) The small business size standard is $5 million. (2) The small business size standard for a concern which submits an offer in its own name, other than on a construction or service contract, but which proposes to furnish a product which it did not itself manufacture, is $5 million. (c) This requirement is NOT set-aside for Small Business. However, the Federal Acquisition Regulation (FAR) requires in every solicitation (except for foreign acquisitions) the inclusion of the Standard Industrial Classification (SIC) Code and corresponding size standard which best describes the nature of the requirement in the solicitation. 2. NUMBER AND TYPE OF AWARD(S) (NIH 2980) (APR 1984) It is anticipated that one (1) award will be made from this solicitation and that award will be made on or about June 30, 1998. It is anticipated that the award from this solicitation will be multiple-year cost reimbursement, completion type contract with a period of performance of 5 years, and that incremental funding will be used [see paragraph (6) of Business Proposal Instructions, in the "Standard RFP Instructions and Provisions" of the Gopher RFP]. 3. ESTIMATE OF EFFORT (NIH 2985) (APR 1984) It is expected that a completion type contract will be awarded as a result of this RFP. To assist you in the preparation of your proposal, the Government considers the total effort to perform this contract to be approximately 7,050% (1,410%/year). This estimate is furnished for your information only and is not to be considered restrictive for proposal purposes. As further assistance, it is estimated that the above total labor effort is constituted as follows: Labor Effort* Category Percent Effort/Yr. x 5 Years = TOTAL -------- ------------------ ----- Professional Staff: P.I. 15% 75% Co-Investigators 45% 225% Other Professional Staff 450% 2,250% Support Staff: Technical Staff 900% 4,500% ---- ------ TOTAL 1,410% 7,050% * Effort in the above chart was based on 100% effort (1 full-time equivalent = 2,080 hours per year), which includes holidays and other paid absences. If you are using a different base, please state the work year used in your proposal. The above labor effort is the Government's estimate of what will be necessary to satisfactorily accomplish the objective(s) of this requirement and will be used as a basis for negotiations. Please provide rationale if you propose deviations from this estimated labor effort. 4. PACKAGING AND DELIVERY OF THE PROPOSAL (NIH 2995) (JUL 1994) Shipment and marking shall be as indicated below: External Package Marking: ------------------------- In addition to the address cited below, mark each package as follows: "RFP No. NIH-NIAID-DAIDS-98-14" "TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY" Number of Copies: ----------------- PLEASE NOTE - THE TECHNICAL PROPOSAL SHALL BE SENT IN SPLIT SHIPMENTS TO TWO LOCATIONS. PLEASE READ THE FOLLOWING INFORMATION CAREFULLY: A. TECHNICAL PROPOSAL ONLY ORIGINAL* AND 4 COPIES TO: If hand delivered or delivery service: -------------------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 If using U.S. Postal Service: ---------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 20 COPIES TO: If hand delivered or delivery service: -------------------------------------- SCIENTIFIC REVIEW PROGRAM (Review Processing Unit) DEA, NIAID, NIH Solar Building, Room 4C15 6003 Executive Boulevard Rockville, Maryland 20852 If using U.S. Postal Service: ----------------------------- SCIENTIFIC REVIEW PROGRAM (Review Processing Unit) DEA, NIAID, NIH Solar Building, Room 4C15 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 B. BUSINESS PROPOSAL ORIGINAL* AND 4 COPIES TO: If hand delivered or delivery service: -------------------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 If using U.S. Postal Service: ----------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 * THE ORIGINALS MUST BE READILY ACCESSIBLE FOR DATE STAMPING PURPOSES NOTE: The U.S. Postal Service's "Express Mail" does not deliver to the Rockville, Maryland address. Any package sent to the Rockville address via this service will be held at a local post office for pick-up. THE GOVERNMENT IS NOT RESPONSIBLE FOR PICKING UP ANY MAIL AT A LOCAL POST OFFICE. If a proposal is not received at the place, date, and time specified herein, it will be considered a "late proposal" and handled in accordance with PHSAR 352.215-10 LATE PROPOSALS, MODIFICATIONS OF PROPOSALS AND WITHDRAWALS OF PROPOSALS (NOV 1986). 5. GOVERNMENT NOTICE FOR HANDLING PROPOSALS An Offeror shall place this notice on the top of each copy of its technical proposal. "This proposal shall be used and disclosed for evaluation purposes only, and a copy of this Government notice shall be applied to any reproduction or abstract thereof. Any authorized restrictive notices which the submitter places on this proposal shall also be strictly complied with. Disclosure of this proposal outside the Government for evaluation purposes shall be made only to the extent authorized by, and in accordance with, the procedures in HHSAR paragraph 315.608-72." (For information regarding authorized restrictive notices, offerors should refer to the "Confidentiality of Proposals" section of the STANDARD RFP INSTRUCTIONS AND PROVISIONS subdirectory of the RFP REFERENCES directory of the Gopher RFP). 6. 52.233-2 SERVICE OF PROTEST (NOV 1988) (a) Protests, as defined in Section 33.101 of the Federal Acquisition Regulation, that are filed directly with an agency, and copies of any protests that are filed with the General Accounting Office (GAO) or the General Services Administration Board of Contract Appeals (GSBCA), shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgment of receipt from: Mr. Lewis Pollack Hand-Carried Address: -------------------- NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 Mailing Address: ---------------- NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 (b) The copy of any protest shall be received in the office designated above on the same day a protest is filed with the GSBCA or within one day of filing a protest with the GAO. 7. PHS 352.223-70 SAFETY AND HEALTH (a) In order to help ensure the protection of the life and health of all persons, as well as to help prevent damage to property, the Contractor shall comply with all Federal, State, and local laws and regulations applicable to the work being performed under the contract. These laws are implemented and/or enforced by the Environmental Protection Agency, Occupational Safety and Health Administration, and other agencies at the Federal, State, and local levels (Federal, State, and local regulatory/enforcement agencies). (b) Further, the Contractor shall take or cause to be taken such additional safety measures as the Contracting Officer, in conjunction with the project or other appropriate officers, determines to be reasonably necessary. If compliance with such additional safety measures results in an increase or decrease in the cost or time required of performance of any part of work under this contract, an equitable adjustment will be made in accordance with whichever applicable "Changes" Clause as set forth in this contract (FAR 52.243-1, Changes-Fixed Price; FAR 52.243-2, Changes-Cost-Reimbursement; or FAR 52.243-3, Changes-Time and Materials or Labor-Hours). (c) The Contractor shall maintain an accurate record of, and promptly report to the Contracting Officer, all accidents or incidents resulting in the exposure of persons to toxic substances, hazardous materials or hazardous operations; the injury or death of any person; and/or damage to property incidental to work performed under the contact and all violations for which the Contractor has been cited by any Federal, State, or local regulatory/enforcement agency. The report shall include a copy of the notice of violation and the findings of any inquiry or inspection, and an analysis addressing the impact these violations may have on the work remaining to be performed. The report shall also state the required action(s), if any, to be taken to correct any violation(s) noted by the Federal, State, or local regulatory/enforcement agency and the time frame allowed by the agency to accomplish the necessary corrective action. (d) If the Contractor fails or refuses to comply promptly with the Federal, State, or local regulatory/enforcement agency's directive(s) regarding any violation(s) and prescribed corrective action(s), the Contracting Officer may issue an order stopping all or part of the work until satisfactory corrective action (as approved by the Federal, State, or local regulatory/enforcement agencies) has been taken and documented to the Contracting Officer. No part of the time lost due to any such stop work order shall be subject to a claim for extension of time or costs or damages by the Contractor. (e) The Contractor shall insert the substance of this clause in each subcontract involving toxic substances, hazardous materials, or hazardous operations. Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor. 8. 52.227-6 ROYALTY INFORMATION (APR 1984) (a) Cost or charges for royalties. When the response to this solicitation contains costs or charges for royalties totaling more than $250, the following information shall be included in the response relating to each separate item of royalty or license fee: (1) Name and address of licensor. (2) Date of license agreement. (3) Patent numbers, patent application serial numbers, or other basis on which the royalty is payable. (4) Brief description, including any part or model numbers of each contract item or component on which the royalty is payable. (5) Percentage or dollar rate of royalty per unit. (6) Unit price of contract item. (7) Number of units. (8) Total dollar amount of royalties. (b) Copies of current licenses. In addition, if specifically requested by the Contracting Officer before execution of the contract, the offeror shall furnish a copy of the current license agreement and an identification of applicable claims of specific patents. 9. PROPOSAL INTENT RESPONSE SHEET PROPOSAL INTENT --------------- RFP No.: NIH-NIAID-DAIDS-98-14 PLEASE REVIEW THE ATTACHED REQUEST FOR PROPOSAL. FURNISH THE INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY OCTOBER 14, 1997. YOUR EXPRESSION OF INTENT IS NOT BINDING BUT WILL GREATLY ASSIST US IN PLANNING FOR PROPOSAL EVALUATION. ================================================================ [ ] DO INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING: __________________________________________________________ __________________________________________________________ [ ] DO NOT INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING REASONS: __________________________________________________________ __________________________________________________________ TYPED NAME AND TITLE: _______________________________ INSTITUTION: ________________________________________ SIGNATURE: __________________________________________ TELEPHONE NO.: ______________________________________ DATE: _______________________________________________ - - - - - - - - - - - - - - - - - - - - - - - COLLABORATORS/CONSULTANTS - Provide name(s) and institution(s): ________________________________________________________________ ________________________________________________________________ ________________________________________________________________ (Continue list on reverse if necessary) RETURN TO: CMB, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 Attn: Grace Bruce RFP NIH-NIAID-DAIDS-98-14 Fax# 301/402-0972 PLEASE RETURN BY: OCTOBER 14, 1997 ************************************************************ ******************************************************************** RFP-NIH-NIAID-DAIDS-98-14 ATTACHMENT E APPLICABLE RFP REFERENCES ------------------------------ This section identifies the items located in the Gopher directory (gopher://gopher.nih.gov/11/res/rd-rfp/rfpref.c) that are applicable to this RFP. 1. The entire file entitled "STANDARD RFP INSTRUCTIONS AND PROVISIONS" is applicable to this RFP, except as otherwise may be modified by the inclusion of an item from the "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS" (below). 2. The following items are applicable from the file entitled "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS": - LATE PROPOSALS, MODIFICATIONS OF PROPOSAL, AND WITHDRAWALS OF PROPOSALS, PHS 352.215-10 - SMALL, SMALL DISADVANTAGED AND WOMEN-OWNED SMALL BUSINESS SUBCONTRACTING PLAN, FAR 52.219-9 [NOTE: A Subcontracting Plan is not due with the initial proposal. The Contracting Officer will notify offerors if a plan becomes due.] - INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS 3. The following items are applicable from the subdirectory entitled "FORMS, FORMATS, AND ATTACHMENTS": APPLICABLE TO TECHNICAL PROPOSAL -------------------------------- (1) Technical Proposal Cover Sheet (2) Technical Proposal Cost Information, Dec 1988 (3) Summary of Current and Proposed Activities, July 1995 APPLICABLE TO BUSINESS PROPOSAL ------------------------------- (4) Contract Pricing Proposal, SF-1411, (Rev. 10/95) (5) Proposal Summary and Data record, NIH-2043 (Rev. 6/82) (6) Business Proposal Cost Information (7) Disclosure of Lobbying Activities, OMB SF-LLL TO BECOME CONTRACT ATTACHMENTS ------------------------------ (8) Invoice/Financing Requests Instructions for NIH Cost- Reimbursement Type Contracts, NIH(RC)-1, JUN 1992 (9) Instructions for Completing Form NIH 2706 (Financial Report (10) Procurement of Certain Equipment, NIH(RC)-7 (11) NIH Women and Minority Policy OTHER - TO BE SUBMITTED AS DIRECTED BY CONTRACTING OFFICER ---------------------------------------------------------- (12) Certificate of Current Cost or Pricing Data, NIH-1397 (13) Subcontracting Plan 4. The Representations and Certifications are applicable and a completed copy must be submitted with offeror's business proposal. 5. The "Sample Contract Format-General" is applicable. ****************************************************************** End of document