SOURCES SOUGHT
R -- Development of Avian Paramyxovirus (APV) Vaccine Vectors
- Notice Date
- 4/18/2005
- Notice Type
- Sources Sought
- NAICS
- 541990
— All Other Professional, Scientific, and Technical Services
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute of Allergy & Infectious Diseases/AMOB, 10401 Fernwood Drive, Suite 2NE70, MSC 4811, Bethesda, MD, 20817
- ZIP Code
- 20817
- Solicitation Number
- Reference-Number-SS-NIAID-05-01
- Response Due
- 5/3/2005
- Archive Date
- 5/18/2005
- Description
- The National Institute of Allergy and Infectious Diseases, Division of Intramural Research, seeks Capability Statements from qualified sources to provide the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to characterize naturally occurring avian paramyxoviruses (APV) and identify strains suitable for further development as vaccine vectors to express antigens of highly pathogenic agents for human immunization. Specifically, this contract will support pre-clinical work to identify APV that are infectious and attenuated in non-human primates acting as surrogates of humans, that are not highly pathogenic in birds, that replicate in Vero cells, and that can be made into recombinant form and engineered to express antigens of highly pathogenic human viruses to induce satisfactory immune responses in non-human primates. Specifically, the Contractor shall: A. Prepare working pools of APV (in particular avian parainfluenza viruses and avian metapneumoviruses). The contractor shall obtain strains of APVs that have been selected by the Project Officer in consultation with the contractor. We anticipate a total of 12-15 serotypes or subgroups, and when possible at least two representatives of each will be acquired. The contractor will secure all necessary USDA and other approvals. It is anticipated that, for tasks A-F, the contractor will move the viruses through the pipeline in groups of 4-6 viruses, as determined by the Project Officer in consultation with the contractor. A small working stock (40 1-ml vials of 106 PFU/ml or greater) of each virus (total of ~30 viruses) will be made in eggs (specific pathogen free SPAFAS) or avian cells (such as DF-1 cells or primary chicken embryo cells, verified to be mycoplasma free) supplied by the contractor. The virus preparations also will be tested for their ability to replicate in Vero cells as part of this initial characterization. The final working stock will be confirmed to be mycoplasma free and, if not, will be passaged with antibiotics to achieve that state, in consultation with the Project Officer. If more than a single passage is required to prepare the working stock, at least 5 1-ml aliquots of each passage level will be preserved. To preclude cross-contamination, viruses will be manipulated separately and careful decontamination and isolation procedures will be followed during all biological cloning and virus preparation procedures. Protocols for this and all subsequent steps will be approved by the Project Officer. Approximately eight working pools will be prepared in the first contract year, and the remaining will be prepared in the second and third years. B. Characterize each APV strain with regard to replication in vitro. The contractor will evaluate the kinetics and yield of multi-cycle viral replication in avian cell culture (supplied by the contractor. as noted above) and Vero cells (to be supplied by the Project Officer). Possible requirement for supplementation with exogenous trypsin or allantoic fluid will be evaluated. Conditions for viral titration by plaque titration or limiting dilution will be established. Approximately eight viruses will be examined in the first contract year, with the remainder examined in years 2-4. C. Antigenic analysis. Virus-specific post-infection serum will be prepared for each virus preparation in chickens or other suitable avian host, and the viral strains will be analyzed in vitro for cross-reactivity by hemagglutination inhibition and virus neutralization assays. From these initial analyses, it is anticipated that approximately 15 viruses will be chosen for further study. Selection will be made by the Project Officer in consultation with the contractor. Approximately six viruses will be examined in the first contract year, eight in year 2, and the remainder in years 3-5. D. Prepare biologically cloned virus suspensions. Strains (approximately 15) will be biologically cloned in cell culture by three rounds of plaque assay or limiting dilution and virus preparations will be made: these typically will consist of 200 1-ml vials of 107 PFU/ml or greater per specimen. These will be confirmed to be free of contamination by fungi, bacteria and mycoplasma. Virus samples from each cloning step will be preserved. The selection of the strains to be analyzed will be made by the Project Officer in consultation with the contractor. Four cloned preparations will be prepared during the first contract year, six during the second year, and the remainder during years 3-5. E. Replication and pathogenicity in birds and embryonated eggs. Viruses will be evaluated for replication and pathogenicity in chickens or other suitable avian host. Animals will be inoculated intranasally, with each group held in isolator cages. Animals from each group (typically 6 per group per time point) will be sacrificed on four time points post-infection and the lungs will be harvested and virus titers assayed to determine the kinetics of pulmonary replication. Next, a group of birds for each virus will be similarly inoculated and, at or closely following the peak of pulmonary replication, animals will be sacrificed at a single time point and tissues (e.g., lung, liver, kidney, intestine, spleen, brain) will be isolated for virus titration. Additional experiment might be done in a few cases involving intracerebral inoculation in young birds followed by sacrifice and virus titration in brain tissue. Viral pathogenicity also will be evaluated in embryonated eggs by standard methods (e.g., mean embryo death time). The selection of the strains to be analyzed will be made by the Project Officer in consultation with the contractor. Two viruses will be examined in year 1, six in year 2, and the remainder in years 3-6. F. Replication in hamsters. Hamsters will be inoculated intranasally and animals (6 per group per time point) will be harvested on three successive days and nasal turbinates and lungs will be harvested and virus titers determined. In some cases, the studies will be repeated and animals will first be immunized by infection with one or more heterologous human viruses (e.g. human parainfluenza viruses types 1, 2 and 3, and mumps and measles viruses, supplied commercially or by the Project Officer) to assess the impact of immunity to common human paramyxoviruses on replication and immunogenicity of APVs. The selection of the strains to be analyzed will be made by the Project Officer in consultation with the contractor. Two viruses will be examined in year 1, six in year 2, and the remained in years 3-5. G. Support LID/NIAID primate studies. The contractor will support eight NIAID studies to evaluate replication, safety, immunogenicity and protective efficacy of selected APVs (or recombinant APVs expressing foreign antigen) in non-human primates. NIAID will have responsibility for purchasing, housing, inoculating, and collecting specimens of the non-human primates; the contractor will provide virus preparations and support these studies by performing quantitative serologic and virologic assays. The non-human primate studies will be performed at a separate LID/NIAID contract facility independent of this proposed contract and at no cost to the proposed contract. Two viruses will be evaluated by the end of year 2 and the remainder in years 3-6. H. Sequence analysis. A complete consensus sequence will be determined for each cloned virus by direct sequencing of uncloned RT-PCR products derived from the biologically cloned preparations. The selection of the strains to be analyzed will by made by the Project Officer in consultation with the contractor. This will total approximately 15 strains. The selection of the strains to be analyzed will be made by the Project Officer in consultation with the contractor. Two viruses will be sequenced by the end of year 2, three in year 3, and the remainder in years 4-6. I. Reverse genetic studies. The contractor will prepare reverse genetic systems for selected APVs and use these reverse genetic systems to recover wild type recombinant viruses. It is anticipated that four such reverse genetic systems will be developed. The selection of strains will be based on the replication in cells in culture or in eggs and on virulence and level of replication in avian and mammalian hosts. Selection of the strains will by made by the Project Officer in consultation with the contractor. One system will be developed by the end of year 2, one in year 3, and the remainder in years 4-6. J. Support construction and analysis of APV-based vectored vaccines. The contractor will assist NIAID in analyzing recombinant APIV/AMPV expressing selected foreign antigen genes. This will involve evaluation for replication and virulence in chickens or other suitable avian host under ABSL-2 or ABSL-3 conditions, as well as similar evaluation in hamsters. It is anticipated that this will involve eight recombinant viruses bearing heterologous inserts. The contractor will consult with the Project Officer in the selection of procedures for each phase of this work, especially those phases in which the recombinant viruses are being recovered for potential administration to humans. One study will initiate in year 1 using materials already developed by the Project Officer. The remaining studies will be done in years 2-6. K. Studies with highly pathogenic agents. The contractor or agent thereof will have Select Agent and USDA clearance for working at ABSL-3 with highly pathogenic avian influenza virus, including H5 and H7. Beginning with H5 virus, a viral sample identified by the Project Officer will be obtained and an influenza virus preparation will be prepared suitable for evaluation in chickens and mice/hamsters. One or two additional, antigenically divergent influenza virus strains all will be selected. These viruses will be used in challenge studies to evaluate the protective efficacy of vectored antigens of avian influenza virus H5. As appropriate, other highly pathogenic agents of BSL3 containment may subsequently be chosen for analysis in conjunction with vectors expressing their antigens, with the total number of agents not to exceed three in addition to the H5 strains. These studies will be designed by the Project Officer in consultation with the contractor. L. Maintain records and biological materials. The contractor will maintain a system of records for all materials and sequences that are prepared. The contractor will develop and maintain a system of storage for all of the biological materials that are generated, particularly viral seed preparations and reverse genetic reagents. All viruses will be maintained at ?70?C or below. Viruses, antisera, cDNA clones, and other materials will be provided to the Laboratory of Infectious Diseases. The contractor will distribute these materials to third parties at the direction of the Project Officer. M. Delivery of results and materials. Sequences and assay results will be transmitted electronically within one (1) week of the date of completion of the analysis in order to accomplish the goals of this contract. Completed virus suspensions and cDNA stocks will be delivered within one (1) week of request. Any potential offeror must be able to document the experience and capabilities of professional and technical personnel that would be assigned to this project. The professional and technical personnel shall have extensive experience in the preparation of viruses, in particular APV, and their analysis in vitro; experience in the use of experimental animals, including virus infection and harvesting of tissues for virus titration; experience in sequence analysis and cDNA preparation and cloning of viral genomes that have not previously been sequenced; and experience in recovery of paramyxoviruses or comparable viruses using reverse genetics. The Offeror must have the established capability for laboratory work and animals testing (rodents or chickens) at ABSL-2 and ABSL-3, and must have documented experience with viral infection of animals and virus isolation from animals at ABSL-2 and ABSL-3. The Offeror also must have or be able to obtain Select Agent approval for work with highly pathogenic avian influenza viruses (e.g., H5 and H7) as well as approval by the United States Department of Agriculture for work with the above-mentioned highly pathogenic avian viruses as well as with Newcastle disease virus mesogenic strains. Capability statements must identify the nature and size of the organization and must be submitted to the Contracts Specialist listed above. Both current and potential government vendors are required to register in CCR (www.ccr.gov) in order to be considered for award of a government contract. This includes Vendors required to complete a one-time registration to provide basic information relevant to procurement and financial transactions. Vendors must update or renew their registration annually to maintain an active status. Both current and potential government vendors are required to register in CCR in order to do be awarded contracts by the government. Additionally, the Federal Acquisition Regulation (FAR) now requires the use of the Online Representations and Certifications Application (ORCA) in Federal solicitations as part of the proposal submission process. ORCA is a web-based system that centralizes and standardizes the collection, storage and viewing of many of the FAR required representations and certifications previously found in solicitations. ORCA gives current and potential government vendors the ability to enter and maintain representation and certification information, at their convenience, via the Internet at http://orca.bpn.gov. *****
- Place of Performance
- Address: Contractor's Site
- Record
- SN00790128-W 20050420/050418211607 (fbodaily.com)
- Source
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