Probing for correlate of protection against SIV/HIV acquisition by the integration of proteome and metabolome with transcriptome analyses.

National Cancer Institute (NCI), Center for Cancer Research (CCR), Vaccine Branch (VB), Animal Models and Retroviral Vaccine Section plans to procure on a sole source basis the services to perform a fully integrated metabolomics and proteomic profiling on 486 plasma samples from macaques immunized that were protected or not against SIVmac251 from BIOASTER; 321 Avenue Jean Jaures; 69007 Lyon, Frances. The response close date of this notice for this requirement is in accordance with FAR 5.203(a)(1). This acquisition will be processed in accordance with simplified acquisition procedures as stated in FAR Part 13.106-1(b)(1), and is exempt from the requirements of FAR Part 6. The North American Industry Classification System code is 621511 and the business size standard is $32.5M. Only one award will be made as a result of this solicitation. This will be awarded as a firm fixed price, type contract. The period of performance will not exceed twelve (12) months from date of award. It has been determined there are no opportunities to acquire green products or services for this procurement. Animal Models and Retroviral Vaccines Section studies the regulation of human T cell leukemia/lymphoma virus type 1 (HTLV-1) replication, focused on the effect of p8 and p12 on T-cell function and viral persistence in vivo, and has begun to investigate the role of pro-inflammatory monocyte subsets that are infected and increased by HTLV-1. The lab has also modeled novel vaccine strategies, such as HPV, heat shock gp96-Ig alone or in combination with the SIV envelope protein to target the mucosa for the prevention of HIV-1/SIV infection. In the last 4 years the lab has refocused on the canarypox-based vector/gp120 boost strategy since this combination has protected humans in the RV144 HIV vaccine trial. The RV144 Thai trial is the first HIV vaccine clinical trial that resulted in significant protection from HIV acquisition. The vaccine regimen included the canarypox-based vector (ALVAC-HIV) and the AIDSVAX HIV Clade B and E gp120 proteins formulated in Alum. The immunological response to this immunization was represented by a low frequency of specific CD4+ T cell responses and high titer binding antibodies to the HIV-1 envelope proteins (Env). Antibodies directed to the variable regions 1 and 2 (V1V2) of Env inversely correlated with the risk of HIV-1 infection. In addition, viral sequencing indicated immunologic pressure on two regions of the V2 variable loop resulting in an acquisition sieve effect that substantiated V2 as an important target for an HIV vaccine. Despite the success of the Thai trial, the efficacy of this vaccine was limited, waned over time and no virologic or clinical benefit was observed in vaccinated individuals that became infected with HIV. With the ultimate goal to improve the efficacy of this vaccine regimen for humans, NCI used a rhesus macaque model of mucosal transmission and demonstrated that the RV144-like vaccine regimen in macaques significantly decreased the risk of SIV acquisition following intra-rectal or vaginal challenge exposure to low repeated doses of SIVmac251. NCI also retained vaccine protection in a cohort of Indian rhesus macaques that were primed with DNA rather than ALVAC/SIV or immunized with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig (gp96SIVIg) carrying SIV peptides boosted with the recombinant envelope protein SIVgp120). In contrast, when NCI tried to improve the protection of the ALVAC/SIV - gp120/Alum by changing the adjuvant (Alum with MF59), or the recombinant poxvirus vector (ALVAC with NYVAC), the prime (DNA with Ad26) or the antigen and the adjuvant (from SIV to HIV Clade C antigens and from Alum Hydrogel to another Alum adjuvant), we did not decrease the risk of SIVmac251. Several canonical immune responses were measured but only antibodies to the envelope correlated with protection. The NCI performed microarray analysis on total RNA from PBMCs obtained from animals immunized with the ALVAC-SIV/gp120/Alum regimen which revealed that 12 genes correlated with protection and among them 5 belonged to the RAS pathway. Meta-analysis of all protective SIV vaccine combinations confirmed the correlation between the decreased risk of SIV acquisition and RAS signaling. The RAS pathway is central to T-cell development and signaling and ERK, one of the most important the downstream effector of RAS is constitutively activated in monocytes. Contractor shall perform a fully integrated metabolomics and proteomic profiling on 486 samples (150 microliters of plasma collected before and after the completion of vaccination, that do not contain SIVmac251): 1. Metabolite profiling will be performed in LC-MS on High Resolution mass spectrometer and in 1H-NMR, and after polar and non-polar sample extraction in order to cover the whole metabolite composition. The LC system will allow the separation of the metabolites which are detected by the mass spectrometer using Full Scan MS and MS/MS methods, in positive and negative modes. For each metabolite, the Contractor shall obtain the m/z values with high mass accuracy, allowing highest confidence for metabolites annotation and shall use an algorithm to search metabolites from databases. Metabolite annotation and database search shall be performed. 2. Identification of proteins shall be performed using the bottom-up proteomic method. Extraction of soluble proteins shall be performed by filtration of the plasma sample to separate the LMW protein faction from the HMW one. LMW proteins filtrate shall be precipitated and in-solution trypsin digestion shall be performed on the protein pellet. The generated peptides shall be analyzed on the Q-ToF Maxis HD LC-HRMS system and protein identification shall be performed using in-house developed software. 3. Signatures from transcriptomics data (previously generated and provided by the NIH) and metabolomics/proteomics data generated in this study data shall be integrated during bioinformatics/biostatistics analyses, based on already available commercial/public solutions, but also on internally developed bioinformatics tools and workflows. 4. The biomarkers identified shall be validated by the Government by performing the appropriate biological experiments in-vivo and additional in-vitro experiments in appropriate cellular models. 5. The Contractor shall provide an interim report on the preliminary results 12 weeks after initiating the analysis of plasma samples. This report shall include information on the number of samples measured thus far, and quality on the results ascertained to date 6. Results on Quality Control samples as well the experimental samples provided by the government to the contractor in each batch shall be provided in an accessible format (such as .xlsx, .dta, or .csv, powerpoint) no later than the expiration date of the award. 7. All samples shall be clearly labeled with the identification of the animals and the date of collection 8. All biological materials provided by the U.S. Government, all residual specimens, and all data generated shall be the property of the U.S. Government and returned upon completion of the study. The proposed vendor, BIOASTER, is the only known entity to perform integrated metabolomics & proteomics on the exact same sample. Known clinical research organizations (CROs) are specialized in either metabolomics or proteomics and cannot perform both types of analyses which make data integration and correlation very cumbersome. In addition, more sample is needed to perform the complete analysis. NCI has limited sample available. At BIOASTER, integrated Metabolomics & Proteomics include Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) analyses. To NCIs knowledge, no CROs offer both NMR and MS for metabolomics profiling. As a result, other entities offer a limited coverage of Metabolites with their analyses. In addition, the staff at BIOASTER has bioinformatics and biostatistics expertise. This notice is not a request for competitive quotation. However, if any interested party, especially small businesses, believes it can meet the above requirement, it may submit a capability statement, proposal, or quotation, which shall be considered by the agency. The statement of capabilities and any other information furnished must be in writing and must contain material in sufficient detail to allow the NCI to determine if the party can perform the requirement. Responses must be received in the contracting office by 3:00PM EDT, on September 23, 2015. All responses and questions must be in writing and faxed (240) 276-5401 or emailed to Seena Ninan, Contracting Officer via electronic mail at ninans@mail.nih.gov. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. No collect calls will be accepted. In order to receive an award, Contractors must be registered and have valid, current Entity Record, including current Representations and Certifications, in the System for Award Management (SAM) through SAM.gov. Reference: NCI-3842027on all correspondence.