B -- Study to evaluate effective vaccines against the virus that causes AIDS.

The Centers for Disease Control (CDC), NCHSTP,DHAP, plans to conduct negotiations on a sole source basis with Caribbean Primate Research Center and Unit of Comparative Medicine (CPRC, UPR), for a study that will further the efforts to evaluate effective vaccines against the virus that causes AIDS.BACKGROUND Appropriate animal studies are a critical adjunct to the evaluations of HIV 1 vaccine strategies as an active prevention approach. Evaluation of safety and immunologic responses to candidate vaccines are necessary assurances prior to Phase I human trials. Furthermore, animal response profiles to different vaccine candidates and to immunization schedules can give important insight into the best candidate vaccine to move forward to human trials. From an earlier completed project 2 vaccine candidate strategies based on naked DNA technology and a prime-boost regimen have been given to rhesus macaques and compared for elicited immune responses. In addition, following mucosal challenges with live virus, we have documented protective effects of these vaccine strategies. The current study proposal is a design for an additional 6-month monitoring period and virus re-challenges of these same vaccinated animals beginning at week 18 post their first virus challenge. This study design will allow for a more in-depth understanding of the vaccine-induced protective effects observed in these animals. The proposed use of 18 animals incorporated into this design permits the evaluation of vaccinated animals (two groups of 8 vaccinees) along with na've control animals (n=2). Monitoring the course of immunologic responsiveness post-vaccination will include longitudinal specimen collections through 6 months for vaccine-induced T-cell responses, serologic responses, and hematologic changes (e.g., CD4 & CD8 T cells) indicative of an adverse response to vaccination. In addition, monitoring the outcome after virus exposure will include longitudinal specimen collections through 6 months for virus levels in plasma (& possibly rectal wash specimens), provirus detection in PBMC, peripheral virus isolations, serologic responses, and hematologic changes (e.g., CD4 & CD8 T cells). A study involving rhesus macaques (Macaca mulatta) is appropriate due to the susceptibility of this macaque species to a variety of human pathogens including HIV-like retroviruses The complex nature of host responses and vaccine product expression and antigen presentation requires the use of live animals to address the research aims in this study. In vitro studies have always preceded in vivo experiments to minimize the number of animals used in our research and the experimental approaches are designed to provide the best possible model for human retroviral infection. Given the highly reproducible rate of retroviral infection among our experimental animals, the utility of such a system as an animal model for studies of vaccine efficacy is clear. All specimen collection procedures for this investigation will be performed by trained staff at an approved regional primate center. Expert CDC staff will likely participate in a quality exchange of selected techniques used successfully here at CDC. PURPOSE To monitor HIV vaccinated macaques that have been challenged with virus to explore lasting protective effects of the vaccination regimen. To continue to maintain and monitor sixteen (18) adolescent macaque monkeys. Knowledge gained from this study will be valuable for the formulation of vaccines against HIV-1 in humans. SCOPE The vendor shall provide all labor, materials and equipment required to house and maintain sixteen (18) macaques in accordance with federal regulations for research animal use and care. Vendor shall provide all laboratory supplies necessary for daily monitoring and monthly physical examinations and shall perform evaluations as outlined in the following tasks. TASKS The vendor shall perform the following tasks: A. Administer virus re-challenges to vaccine-protected macaques with an inoculum containing SHIV162p up to a maximum of 8 doses over the course of 6 months. B. Collect and monitor blood samples from monkeys, following the appropriate bleeding schedule, for 6 months total. Blood samples shall be monitored for the following: 1. Frequency and absolute numbers of CD4+ and CD8+ T cells 2. Hematologic chemistry and CBC, at described frequencies C. Monitor animal health for symptoms of adverse reactions, as characterized by hemogram abnormalities, cachexia, loss of CD4+ T cells, etc. These animals shall be monitored for 6 months unless they develop severe adverse reactions as described resulting in loss of body weight of 25% for two consecutive months. If that occurs, they shall be euthanized. D. At the bleeding schedule provided, collect, process, package and ship blood samples for overnight delivery to Dr. Ron Otten, CDC, for in vitro virologic & immunologic evaluations. Samples are to be shipped in accordance with IATA regulations (http://www.iata.org/index.htm). E. Prepare reports reflecting the results of monitoring and testing. Reports are to be sent electronically to the Project Officer: 1. Interim Reports: to be provided at the end of each 3-month period. 2. Final Report: to be provided at the end of the 6-month performance period. CURRENT EXPERIMENTAL GROUPS Group # # of animals HIV Vaccinated Current Status 1 2 None Na've Controls 2 8 Yes (IC25 construct) Vaccine Primed 3 8 Yes (IC48 construct) Vaccine Primed STUDIES TO BE PERFORMED Week* Virus Re-challenges CBC** FACS** Clinical Chemistry Virology & Serology Rectal Wash LN biopsy 18 X 20 X X 24 X X X X X 28 X X X 29 X 30 X X X X X X 31 X 32 X X X 33 X 34 X X X 35 X 36 X X X X X X 40 X 44 X X X X X Volume of whole blood/timepoint 0.5 ml 0.5 ml 1.5 ml 8mL*** Anticoagulant EDTA EDTA none CITRATE Type of tube regular regular SST CPT *Evalution study begins at Week 18 post first virus inoculation of the vaccinated animals ** this blood collection can be in the same tube (total of 1mL) when scheduled on the same week. *** this volume will be within the 6.6ml/kg/21day maximum which would be 11mL total per week for a 5kg monkey. All macaques in this study are at least 5kg. Species and Strain. Macaca mulatta (rhesus monkey) Route of administration for virus re-challenges. Intrarectal (IR) injection with a sterile 5cc syringe attached to a sterile gastric feeding tube (size 5 or 8 French) of adjusted length. Frequency for virus re-challenges Eight inoculations during this study (weeks 28-35; see Table). Volumes. 1 mL for virus inoculation Frequency for blood collections. Routine collections from week18-44 (see Table). Frequency for rectal wash collections. Variable collections from week 18-44 (see Table). Experimental Duration. 6 months total (200d) Evaluation Parameters. Clinical observations recorded at each animal access prior to virus inoculation. Body weights and temperature recorded at each animal access for blood collection. Clinical Pathology. CBC and blood chemistry at routine intervals (see Table). FACS analysis for total T, total B and T cell subsets at routine intervals (see Table). Necropsy of selected animals will be scheduled towards the end of this study. Also, if any animal dies or needs euthanasia, necropsy and histopathologic examinations will be conducted. GOVERNMENT FURNISHED PROPERTY Sufficient virus stock to complete the study outlined in the statement of work. CPT (citrate) blood collection tubes for the entire study. Sterile 5cc syringes & sterile gastric feeding tubes to carry out the virus inoculations outlined in the statement of work. PERIOD OF PERFORMANCE The period of performance shall commence upon receipt of the purchase order and shall continue for 6 months. DELIVERABLES The vendor shall provide the following deliverables to the Project Officer by the dates required. Deliverable Due Date A. Report of Results of Monitoring and Testing Interim reports due after each 3-month period Final report due at end of 6 months B. Specimens To be shipped overnight after collection. Please refer to table (see above) for specifics on specimen collections OTHER REQUIREMENTS Vendor authorizes CDC unrestricted use of this data. MINIMUM VENDOR QUALIFICATIONS Knowledge of laws, regulations, and guidelines pertaining to housing, maintaining, and conducting research involving rhesus macaques (both na've & virus-infected) as evidenced by regional primate center designation. MINIMUM REQUIREMENTS AND WHY THESE MINIMUM REQUIREMENTS ARE NECESSARY TO FULFILL THE NEEDS OF CDC. Reliability, knowledge and experience in housing, maintaining and conducting research involving rhesus macaques as evidenced by Regional Primate Center designation. CDC, as a part of the federal scientific research establishment that is responsible for developing guidelines for the ethical care and use of animals in research, must uphold the highest possible standards in its use of animals in research studies and collaborate only with other scientists and institutions that are required to uphold the same high standards. Therefore, the minimum requirement for a vendor for this work is that the vendor be designated a regional primate center. This designation ensures that the facility meets government standards for the type and size of animal cages and housing conditions; the qualifications and training of veterinarians, research scientists, technicians, and animal handlers; the quality of the animal care and feeding; and the protection of the animals used in research procedures from unnecessary harm. Government funded regional primate centers also require that research protocols involving animals are reviewed by an institutional animal care and use committee, which additionally insures careful and efficient use of animals in research protocols. In addition, this project requires 18 rhesus macaques (Macaca mulatta) due to the susceptibility of this macaque species to a variety of human pathogens including HIV-like retroviruses. Previous HIV research experience is also required. CPRC has specialized in the breeding, husbandry, and research use of rhesus macaques (Macaca mulatta) that can be traced back to 1938. The susceptibility of this macaque species to a variety of human pathogens including HIV-like retroviruses, in this case, make it advantageous and the hallmark nonhuman primate to use for our outlined studies. Thus, CPRC offers a highly valuable resource and much needed expertise in this area of CDC-sponsored research. CAPABILITIES REQUIREMENTS:Through this announcement, potential vendors must demonstrate their capabilities to provide the services specifically identified above. To be considered qualified, sources must submit a capabilities statement, which demonstrates in writing that they have the intricate knowledge of the data needs and programmatic demands of the project and possess the following expertise in: 1) housing and maintenance of Macaca mulatta (rhesus macaques) in accordance with federal regulations for research animal use and care. 2) HIV research experience. 3) DNA and MVA vaccination using cloned products from HIV-1 subtype A/G strains. 4) administering intrarectal virus challenges to macaques with an inoculum containing SHIV162p. 5)monitoring animal health for symptoms of adverse reactions after virus challenges, as characterized by hemogram abnormalities, cachexia, loss of CD4+ T cells. This expertise should be demonstrated through a combination of publications, track record of completed methodological projects, and invited presentations addressing these topics. Ability to collect, process, package and ship blood samples for overnight delivery in accordance with IATA regulations for in vitro virologic and immunologic evaluations Ability to prepare reports reflecting the results of monitoring and testing. Ability to perform virus challenges and evaluation of macaques within the timeframe specified in the statement of work. Capabilities are to be received in the CDC/NIOSH contracting office no later than fifteen (15) days from the date of this announcement. Submit written information to: Patricia Rose, CDC/PGO/AAFB, 4676 Columbia Parkway, Cincinnati, Ohio 45226, Mail Stop C-4, Reference #000HCK72-2004-11388. Information received will be used solely for the purpose of determining whether to conduct a competitive procurement. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of th Government. This is a simplified acquisition with an estimated value of less than $100,000.