November 17, 2023
None
National Institute of Allergy and Infectious Diseases (NIAID)
The mission of the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID) is to ensure an end to the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic by supporting research that can lead to the development of therapies, vaccines, and prevention strategies. Since the mid-1980’s animal models have played an important role in the Institute’s efforts to achieve its mission.
Nonhuman primate (NHP) models present an opportunity to test a variety of candidate AIDS vaccines, optimizing their ability to elicit immune responses and testing their ability to prevent infection or to control virus replication after virus challenge. NHP models can be used to optimize vaccines, to evaluate vaccine combinations, to determine vaccine delivery routes that provide immune responses at mucosal portals of entry, to find ways to generate broadly cross-reactive neutralizing antibodies, and to determine effectiveness of vaccines. NIAID supports NHP and small animal studies through contract and grant mechanisms.
NIAID supports Core Laboratories that conduct immunology, virology, and transcriptomic assays in support of preclinical animal studies to ensure standardization and comparability of the assays conducted, and to provide a common basis for assessment of the immunogenicity and efficacy of candidate HIV and SIV vaccines.
The current Humoral Immunology Core Laboratory (HICL) provides assays to evaluate a wide range of antibody properties and functions to be able to identify immune correlates of vaccine-generated protection from virus infection and to identify vaccines and adjuvants that can generate protective antibody responses. The HICL supports preclinical NHP studies conducted through the Simian Vaccine Evaluation Unit (SVEU) contracts. It is also available to conduct assays in support of NHP AIDS vaccine studies conducted by non-SVEU investigators but is not intended to conduct assays for human clinical trials. It may support other NHP or other small animal studies. The contract conducts assays to assess the specificity, affinity, and breadth of antibody binding to HIV and SIV antigens and peptides. It conducts HIV, SIV, and SHIV virus neutralization assays for assessment and comparison of the breadth of virus neutralization by antibodies generated by candidate vaccines. It conducts assays to assess the maturation of antibodies in broadly neutralizing antibody lineages after priming and boosting immunizations and conducts assays to identify the target epitopes of binding or neutralizing antibodies. The contract also assesses other, Fc receptor-mediated activities of antibodies, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).
The current HICL contract is held by Duke University Medical Center, Durham, NC, under contract number HHSN272201800004C. The current period of performance ends March 29, 2025.
The purpose of this contract is to conduct, develop, acquire, improve, and implement assays to evaluate and characterize the humoral immune responses of nonhuman primates (NHP) that have been immunized with candidate HIV or SIV vaccines or infected with SIV, SHIV, or HIV, with a focus on studies conducted by the NIAID Simian Vaccine Evaluation Units (SVEUs) and by investigators supported by or collaborating with NIH. This contract may also conduct assays to assess HIV and SIV antibodies in small laboratory animals immunized in studies preliminary to or supportive of vaccine studies conducted in NHPs. The contract may develop, optimize, and conduct humoral immunology assays for other (non-AIDS-related) infectious agents, especially emerging infectious agents that may present risks to public health.
Project Requirements
Offerors should have the qualifications, experience, and capability to perform this requirement. Specifically, the Contractor will be responsible for the following:
1. Conducting assays requested under proposed contract in accordance with GLP standards under the direction of an institutional Quality Assurance office. (GLP described in 21CFR58 Good Laboratory Practice for Nonclinical Laboratory Studies)
A) For NHP studies evaluating human clinical vaccines, conducting virus neutralization assays on the NHP samples using GLP processes in compliance with 21CFR58.
B) New assay development, assay modification, improvement of the level of assay standardization or validation, and evaluation of in vitro/in vivo assay correlations, with the objective of developing a new GLP-compliant assay do not have to be GLP compliant
2. Developing, reviewing, and maintaining detailed laboratory SOPs for all assays to be conducted under the proposed contract. Providing SOPs to the COR following modifications or addition of new SOPs.
3. For each type of assay conducted under the proposed contract:
A) Demonstrating the level of sensitivity and reproducibility of the selected assay, including the level of signal obtained with virus-negative samples from uninfected animals.
B) Including appropriate positive and negative controls with each set of samples assayed to provide quality control and ensure consistency of results of the assay.
C) Conducting comparisons of the assay with assays conducted by other laboratories, as requested by the COR.
D) Determining that test sera are free of any contaminants, such as endotoxin, that may affect the assay results.
4. Conducting Humoral Immunology Assays
Conducting the AIDS-related humoral immunology assays in accordance with GLP standards as requested under the proposed contract. At the direction of the Contracting Officer’s Representative (COR), performing immunological analyses to evaluate and characterize the humoral immune responses of NHPs that have been immunized with HIV or SIV vaccines, or infected with SIV, SHIV, or HIV. The specific assays to be conducted and the samples on which the assays will be conducted will be defined by individual study protocols designed by the vaccine provider, the SVEU staff, and the COR, in collaboration with the HICL Contractor. Additional assays or assay-related studies may be included at the request of the COR. Assays to be conducted include those described below:
A) Antibody Binding Assays
1. Performing assays to detect the presence of HIV or SIV antibodies. These may include enzyme-linked immunosorbent assay (ELISA), binding antibody multiplex assay (BAMA), or other appropriate assays.
2. Performing assays for antibody characterization, such as binding to panels of HIV or SIV envelopes, binding to specific HIV or SIV epitopes, detection of linear or conformational epitopes recognized by antibodies, measurement of the affinity of binding of antibodies to HIV or SIV viral proteins, characterization of IgG and IgA antibodies, identification of epitopes targeted by antibodies, and other assays as requested by the COR.
B) Virus Neutralization Assays
1. Performing virus neutralization assays to determine the ability of sera to neutralize infection of appropriate target cell lines and/or primary cells by SIV, SHIV, and HIV viruses, as appropriate for the relevant study protocol.
2. Determining neutralization titers of sera that show the ability to neutralize HIV, SHIV, or SIV viruses.
3. Determining the breadth of neutralizing activity of sera from HIV (or SIV) vaccine studies. Assays may include determining neutralizing activity against primary isolates of HIV (or Env-pseudoviruses containing the envelopes of primary isolates of HIV-1), including using standard panels of HIV, representing viruses of multiple clades (B, A, C, D, etc.) and representing viruses of varying difficulty of neutralization by sera from HIV-infected persons or monoclonal antibodies. The extent of the evaluation (i.e., the number and size of the virus panels used for the evaluation of the neutralizing activity of the sera) may vary with the study and will be determined in conjunction with the COR. For SIV vaccine studies, determine neutralizing activity against a panel of available SIV viruses.
4. Maintaining virus panels for use in neutralization assays: Obtaining or growing HIV, SHIV, and SIV virus stocks and preparing HIV env-pseudovirus stocks for use in neutralization assays. Determining the in vitro titer of the stocks and demonstrating the extent to which the viruses are able to be neutralized by monoclonal antibodies and/or sera from HIV-infected people or SHIV- or SIV-infected monkeys prior to conducting neutralization assays with the sera from the vaccine studies. The selection of virus stocks to be prepared shall be approved by the COR.
C) Assays for Fc-R mediated antibody functions
1. Conducting assays to evaluate other, non-neutralizing activities of antibodies, including monoclonal antibodies and antibodies present in sera of immunized or infected animals. These could include such activities as antibody-dependent cellular cytotoxicity (ADCC) assays, antibody-dependent cellular phagocytosis (ADCP) assays, or antibody-dependent cell-mediated virus inhibition assays (ADCVI), or other assays, at the direction of the COR.
2. Conducting evaluations to identify characteristics of ADCC or ADCP-mediating antibodies, and/or to characterize the NHP effector cell populations mediating the functions.
D) Mucosal Antibody Assays: Performing assays to evaluate and characterize immune responses at mucosal sites in NHP that have been immunized with HIV or SIV vaccines or infected with HIV, SHIV, or SIV. Specifically:
1. Performing assays to detect and measure HIV-specific or SIV-specific antibodies (IgG, IgA, and secretory IgA antibodies) in mucosal secretions such as vaginal and rectal swabs/washes and saliva of immunized or infected macaques.
2. Performing assays to detect and measure HIV-specific or SIV-specific antibody-secreting cells in mucosal tissue, such as vaginal and rectal tissue, of immunized or infected macaques.
3. Conducting assays to evaluate functional humoral immune responses (such as virus neutralization assays) in mucosal secretions or mucosal tissues of immunized or infected macaques, as appropriate assays are developed or become available.
5. Sample Receipt and Storage
A) Receiving, cataloging, tracking, and maintaining an electronic inventory of the samples shipped to the Contractor’s laboratory for evaluation. Tracking samples from study site, receipt, sample processing, storage, the conduct of assays, analysis and reporting of assay results, and disposition of samples. Specific activities will include:
1. Providing detailed procedures for shipping to investigators who provide samples for evaluation so that activity/viability of samples will be maintained.
2. Developing shipping forms for collecting samples and identifying information. Providing the shipping forms to investigators so that the forms can be included with sample shipments.
3. Coordinating sample shipment from investigators to the Contractor’s facility or as specified by the COR.
4. Tracking the shipments throughout transit.
5. Receiving and cataloging incoming samples, and maintaining information for each sample, including study site sending the sample, study protocol identification number, primate identification number, type of specimen, specimen collection date, condition of sample upon arrival, storage location, and sample disposition.
B) Storing samples under appropriate conditions, including temperature, to retain maximum immunological and biological activity.
C) Maintaining security and safeguards of samples, including 24-hours a day/seven days a week monitoring of refrigerator and freezer conditions by automatic temperature alarm systems to guarantee continuous proper storage of the samples. Maintaining back-up storage capability in the event of individual freezer failure, or power failure.
6. Management and Reporting of Study Data
A) Maintaining an electronic record of all assay results. Results are to be recorded with designations of type of assay, study protocol number, animal number, specimen collection date, assay date, and other information requested by the COR.
B) Reporting data and results to the COR, to collaborating study investigators, to other investigators as directed by the COR, to the SVEU Study Database* and/or to a NIAID-designated data repository.
1. Providing electronic (e.g., email), and verbal status reports of the assay results for studies to the COR on an ongoing basis, in addition to the required periodic (quarterly and annual) reports. Data shall be reported in a format approved by the COR.
2. Providing completed assay data and results electronically to the COR, to investigators providing samples, and to designated data repositories.
*Note: Through a separate contract, NIAID maintains a data repository (SVEU Study Database) for the vaccine studies conducted at SVEU sites. The SVEU Database contains information on study design, immunization schedules, virus challenges, assays conducted, and data from the assays conducted in support of the studies.
Anticipated Period of Performance
It is anticipated that a cost reimbursement, term/level of effort, type contact will be awarded. The period of performance will be for one year (Base Period) plus six (6) one-year options to extend the term of the proposed contract that may be exercised by the Government unilaterally, for a total possible period of performance of seven (7) years, beginning approximately January 31, 2025. The requirement will be the delivery of 10.53 full time equivalents (FTEs) per year for the Base Period (Year 1) and 10.53 FTEs per year for Options 1-6 (Years 2-7).
In addition, the Government may exercise options for an increased level of effort that may result from unanticipated increases in demand for the activities supported by the base requirements of the proposed contract. Options for increased services may include:
Options 1 through 6, to Extend the Term of the Contract: The Government may exercise options to extend the period of the proposed contract beyond the base period (Year 1), annually, for a total contract period of up to 7 years. The Contractor shall provide 10.53 Full Time Equivalents (FTEs) for each option exercised. If Options 1-6 are exercised, the services required will be the same as provided during the Base Period.
Options 7 through 20, to Increase Level of Effort: The Government may exercise options for increased level of effort that may result from unanticipated increases in demand. Should the Government elect to exercise these options, the Contractor shall provide resources for the unanticipated increase in work volume by 1.0 FTE plus supporting materials and supplies for each option exercised. These options may be exercised twice per year during Years 1 through 7. The period of performance of an Option for increased level of effort for this purpose will not exceed the term of the Base Period or Option year in which the Option is exercised
Options 21 through 27, to Increase Level of Effort: The Government may exercise options for increased level of effort that may result from unanticipated increases in demand. Should the Government elect to exercise these options, the Contractor shall provide resources for the unanticipated increase in work by 0.5 FTE plus supporting materials and supplies for each option exercised. It is anticipated that only one option will be exercised per performance year. The period of performance of an Option for increased level of effort will not exceed the term of the Base Period or Option year in which the Option is exercised.
Options 28 through 34, to Increase Level of Effort: The Government, at the direction of the COR, may exercise options to acquire, develop, and conduct humoral immune assays to detect, evaluate, and characterize antibodies generated by infection with, or by immunization with vaccines against, pathogens that present a major public health risk. Should the Government elect to exercise these options, the Contractor shall provide 2.0 FTEs, plus supporting materials and supplies, for each option exercised. It is anticipated that only one option will be exercised per performance year. The period of performance of an Option for increased capability/level of effort for this purpose will not exceed the term of the Base Period or Option year in which the Option is exercised.
Any responsible offeror may submit a proposal, which will be considered by the Agency. This RFP will be available electronically, on/about November 17, 2023, and may be accessed through SAM http://sam.gov/. This notice does not commit the Government to award a contract. No collect calls will be accepted. No facsimile transmissions will be accepted.
For this solicitation, the NIAID requires proposals to be submitted online via the NIH’s electronic Contract Proposal Submission (eCPS) website at https://ecps.nih.gov. Submission of proposals by facsimile or e-mail is not acceptable. For directions on using eCPS, go to the website (https://ecps.nih.gov) and then click on "How to Submit."
Christopher Ray
Contract Specialist
AIDS Research Contracts Branch Office of Acquisitions
Division of Extramural Activities
National Institute of Allergy & Infectious Diseases
National Institutes of Health, DHHS
5601 Fishers Lane, Room 3C28, MSC 9821
Bethesda, MD 20892-9821
For Express Mail, change zip code to 20852
Direct Phone: 240-627-3365
Email: [email protected]
Robert Corno
Contracting Officer
AIDS Research Contracts Branch Office of Acquisitions
Division of Extramural Activities
National Institute of Allergy & Infectious Diseases
National Institutes of Health, DHHS
5601 Fishers Lane, Room 3C31, MSC 9821
Bethesda, MD 20892-9821
For Express Mail, change zip code to 20852
Direct Phone: 240-669-5151
Email: [email protected]
and Human Services (HHS)
