Amendment_1_-_NIHAI201800011.pdf

Amendment #1, RFP No. NIAID-DAIDS-NIHAI201800011 1

Amendment No. 1 RFP No. NIAID-DAIDS-NIHAI201800011

“Simian Vaccine Evaluation Units (SVEUs)”

Solicitation Number:

Amendment Number:

Amendment Issue Date:

NIAID-DAIDS-NIHAI201800011

One (1)

January 31, 2019

Issued By: Ashley Virts Contracting Officer

OA/DEA/NIAID/NIH/DHHS

5601 Fishers Lane, Room 3D10, MSC 9821 Bethesda, Maryland 20892-9821

Points of Contact: PRIMARY:

Ashley Virts, Contracting Officer Phone: 240-669-5154 Email Address: virtsa@mail.nih.gov

SECONDARY:

Michelle L. Scala, Contracting Officer Phone: 240-669-5156 Email Address: mscala@niaid.nih.gov

The purpose of this amendment is to provide responses to questions from potential offerors regarding the solicitation.

Offerors must acknowledge receipt of this amendment by identifying this amendment number and date of the amendment on each copy of the proposal submitted. Failure to receive your acknowledgement may result in the rejection of your proposal. Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full force and effect.

Responses to Questions from Potential Offerors:

Question 1:

Will alternate proposals be permitted?

Response to Question 1:

Alternate proposals are permitted. Please see page 46 of the solicitation. Please be advised that separate proposal(s) must be submitted per Task Order, in any instance where the offeror proposes an alternate solution that deviates from the requirements of the Statements of Work in the solicitation. In addition, please review FAR 15.206(d).

file://niaid-fas2/cmbsh/AIDS%20Research%20Contracts%20Branch%20(AIDS%20RCB)/AIDS%20RCB%20-%20Solicitations/FY-19%20RFPs/NIHAI201700103%20-%20VQA%20-%20Gomes/Tab%20D%20-%20Solicitation/Amendment/virtsa@mail.nih.gov mailto:anhughes@niaid.nih.gov

Amendment #1, RFP No. NIAID-DAIDS-NIHAI201800011 2

Question 2:

Can current Task Orders under the incumbent awards be utilized in the past performance data?

Response to Question 2:

Yes.

Question 3:

The period of performance for the current SVEU contract begins May 1; however, this solicitation indicates the start date in February, is this correct?

Response to Question 3:

Any resultant award(s) will be made with a February 1, 2020 start date. Any overlap with the current contract(s) is to allow for transition, if necessary.

Question 4:

Should the Small Business Reporting Plan be based on the maximum amount of the proposal totaling $66,355,351, or rather separate goals per each Task Order being proposed?

Response to Question 4:

The Small Business Subcontracting Plan should be based on the maximum value totaling $66,355,351.

Question 5:

In budgeting for future years, can annual 2% escalation factor be used for items other than salaries?

Response to Question 5:

An escalation factor of 2% is acceptable for budgeting purposes for all proposed Other Direct Costs in future years.

Question 6:

Is it permissible to use a 3% annual escalation factor for salaries?

Response to Question 6:

A 3% escalation factor for salaries is acceptable.

Question 7:

Attachment 12. Additional Business Proposal Instructions (page 7) A discrepancy was found in Task Order 002-2 requesting .06 FTEs per year (see below table).

Should the effort be listed as 1.6 FTE’s? Please confirm.

Response to Question 6:

The effort should be listed at .06 FTEs total. There was an error in the number of estimated FTEs listed for Technical Support in the table on page 7 of Attachment 12, Additional Business Proposal Instructions. The estimate for Technical Support should be reflected as .05 FTEs. The total estimated FTEs per year for Task Order 002-2 is listed correctly as .06 FTEs. Attachment 12 has been revised accordingly.

Labor Category Other Professional .01 Technical Support .05 Total .06

Amendment #1, RFP No. NIAID-DAIDS-NIHAI201800011 3

Question 8:

Task Order 003-1 In the Conduct Assays section and Study Table, there are references to challenge, Option 1, but there are no instructions nor study tables. Can we assume there is no challenge phase in this Task Order?

Response to Question 8:

This sample Task Order is for the evaluation of vaccine immunogenicity only. There is no challenge phase for this study.

Question 9:

Task Order 003-2 Which route will be used for vaccine immunizations (DNA and Protein)?

Response to Question 9:

DNA and protein will both be administered by intramuscular route.

Question 10:

Task Order 003-3 Will there be a period allowed to complete the conduct of assays for the study and for the preparation of study reports (including entry of the study information and data into the SVEU Vaccine Study Database).

Response to Question 10:

Yes. Please include 3-months after the completion of in vivo studies to allow for completion and submission of the study report.

END OF AMENDMENT No. 1

RFP No. NIAID-DAIDS-NIHAI201800011

Attachment 12, Additional Business Proposal Instructions 1 (revised January 30, 2019)

ATTACHMENT 12

ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS

AND UNIFORM COST ASSUMPTIONS

SIMIAN VACCINE EVALUATION UNITS (SVEUs) RFP No. NIAID-DAIDS-NIHAI201800011

In addition to the format requirements for the Business Proposal that are contained in Section L of the solicitation, the information presented in this section of the RFP is intended to provide uniform cost assumptions and business clarifications.

Offerors are advised to give careful consideration to the Statements of Work for Task Orders for Task Areas 1, 2, 3, and 4, all reference material provided as attachments, the Technical Evaluation Criteria, and, the RFP as a whole, in the development of your proposal. The information requested in these instructions should be used as a guide for the development and formatting of your Business Proposal. Offerors should consider and include the information requested here, as well as any other information which will benefit the proposal.

BUSINESS PROPOSAL – TABLE OF CONTENTS

Please note that offerors may submit proposals for Task Areas 1, 2, and 3, or for Task Areas 1, 2, 3 and 4, or for Task Area 4 alone. A Business Proposal may be submitted for Task Areas 1, 2, and 3 but must be separate from the Business Proposal for Task Area 4.

Note: A separate cost proposal/budget spreadsheet must be submitted for each Task Order proposal, including the Task Area 3 Sample Task Orders.

SECTION 1 – PROPOSAL COVER SHEET (use form NIH 2043 identified in Section J)

SECTION 2 – COST OR PRICE SUPPORT

Section L of the RFP specifies the minimum documentation requirements for cost data and all cost related support. All related documentation should be included in the proposal in a clearly marked section.

SECTION 3 – UNIFORM COST ASSUMPTIONS

I. Technical Cost Assumptions

The list below represents the tasks offerors should assume that they will perform each year under the Task Orders, including animal studies that may extend over multiple years. This list is provided to indicate the general scope of the work to be performed.

Immediately upon award of the base contract, the Government intends to award Task Orders in Task Area 1, Core Activities: Administrative and Technical Support, Task Area 2, Maintenance of Nonhuman Primates, and Task Area 4, Operation of a Nonhuman Primate Breeding Colony.

Attachment 12, Additional Business Proposal Instructions 2

Task Area 1, Core Activities: Administrative and Technical Support:

• Up to three (3) Task Orders will be awarded to 3 separate contractors as cost reimbursement, term/level of effort form task orders for a period of 1 year with Options to extend the period of the Task Orders on an annual basis for a maximum period of performance of 7 years. The performance requirement will be the delivery of 1.00 FTE per year. In addition, an Option for Increased Level of Effort to increase the performance requirement by 0.30 FTEs per year may be exercised up to one (1) time per year.

Task Area 2, Maintenance of Nonhuman Primates:

• Up to three (3) Task Orders will be awarded to 3 separate contractors for maintenance of an average of 15 nonhuman primates per year in ABSL2/3 facilities. These Task Orders will be awarded as cost reimbursement, term/level of effort form task orders including a performance requirement for delivery of 0.27 FTEs per Task Order per year. The Task Orders will be awarded for a 1-year period with options to extend the period of the Task Orders annually for a maximum performance period of 7 years. In addition, Options for Increased Level of Effort for delivery of an additional 0.09 FTEs for maintenance of an additional five (5) nonhuman primates per year in an ABSL2/3 facility will be included in this Task Order. Options for Increased Level of Effort may be exercised up to 3 times per year.

• One (1) Task Order will be awarded to 1 contractor for maintenance of 30 nonhuman primates in an ABSL2 facility. This Task Order will be awarded as cost reimbursement, term level of effort form task order including a performance requirement for delivery of 0.06 FTEs. The Task Order will be awarded for a 1-year period with options to extend the period of the Task Order annually for a maximum performance period of 7 years. In addition, Options for Additional Level of Effort for delivery of an additional 0.02 FTEs for maintenance of 10 additional nonhuman primates per year in an ABSL2 facility will be included in this Task Order. Options for Increased Level of Effort may be exercised up to three (3) times per year.

NOTE: Offerors may submit proposals for each of the Task Orders described above (maintenance of 15 NHPs or maintenance of 30 NHPs). Offerors do not have to submit proposals for both of these Task Area 2 Task Orders. If technical proposals are submitted for both, the cost proposals must be submitted as separate documents.

Future Task Orders will be issued as the need for maintenance of additional nonhuman primates arises.

Task Area 3, Conduct of Studies in Nonhuman Primates

• No Task Orders will be issued in Task Area 3 at the time of award of the SVEU contract.

• It is anticipated that four (4) to six (6) Task Orders will be issued per year for Task

Area 3, Conduct of Studies in Nonhuman Primates, as nonseverable completion form task orders with a performance requirement for completion of studies and delivery of a final study report.

Attachment 12, Additional Business Proposal Instructions 3

Task Area 4, Operation of a Nonhuman Primate Breeding Colony

• One (1) Task Order will be awarded to 1 contractor to provide support for appropriate housing, care and maintenance of an average of 500 SPF nonhuman primates per year including breeding harems to achieve a production rate of 60-100 live births per year.

This Task Order will be awarded as a cost reimbursement, term/level of effort form task order including a performance requirement for delivery of 0.50 FTEs. The Task Order will be awarded for a 1-year period with Options to extend the period of the Task Order annually for a maximum performance period of 7 years. In addition, Options for Increased Level of Effort for delivery of 0.05 FTEs per year for maintenance of 50 additional nonhuman primates per year will be included in this Task Order. Options for Increased Level of Effort may be exercised up to one (1) time per year.

NOTE: Offerors must be capable to perform all work in Task Areas 1: Core Activities:

Administrative and Technical Support, Task Area 2: Maintenance of Nonhuman Primates, and Task Area 3: Conduct of Studies in Nonhuman Primates, or the work in Task Area 4:

Operation of a Nonhuman Primate Breeding Colony.

A. Technical Cost Assumptions for Task Orders for Task Area 1: Core Activities:

Administrative and Technical Support:

Immediately upon award of the base contract, NIAID anticipates issuing up to 3 Task Order awards to up to 3 separate contractors for the Core Activities: Administrative and Technical Core Support Task Area. The Contractor must be capable of initiating this Task Order upon award.

Provide a detailed budget for the proposed Task Order using the following assumptions:

It is anticipated that a severable term form contact will be awarded for this Task Order.

The period of performance will be for one year beginning approximately February 1, 2020 through January 31, 2021. The performance requirement will be the delivery of 1.00 FTE per year for the base period (Year 1) and 1.00 FTEs per year for Options 1-6 (Years 2-7). If Options 7-13 are exercised, the requirement will for an additional 0.30 FTEs per year for Years 1-7.

The following total level of effort shall be provided in support of this Task Order. The personnel categories are provided as an estimate and are not meant to be restrictive.

Offerors must provide the specified total level of effort but may propose a different labor mix deemed most appropriate to carry out the Statement of Work.

FTEs/Year

Labor Category Year 1 Principal Investigator .10 Other Professional .50 Technical .40 Total 1.00

Attachment 12, Additional Business Proposal Instructions 4

1. Receipt, Storage and Shipment of vaccines, study samples, virus stocks, and other study-related materials

Appropriate technical, scientific, and administrative personnel will:

a. Receive and store vaccines and other study components, as described in the SOW, assuming storage at room temperature, 40C, -200C, -800C, and liquid nitrogen conditions. Assume the need for storage of approximately 100 vials (1 ml each) for each storage condition.

b. Ship virus stocks to investigators as requested by the COR. Assume monthly shipments of 10 vials, each containing 1 ml virus, in biocontainment shipment containers, on dry ice.

c. Store and maintain an inventory of titered virus stocks under liquid nitrogen conditions. Assume 4 stocks of 600 x 0.5 ml each.

d. Store and maintain an inventory of animal specimens collected during the course of the studies conducted under the Task Orders, at -20°C, -80°C, and/or liquid nitrogen, as appropriate for the samples. Assume the need for storage for approximately 6000 serum samples, 2500 plasma samples, and 1000 viably frozen PBMC samples.

e. Provide monitoring of storage conditions by automatic temperature alarm to guarantee continuous proper storage of virus stocks, candidate vaccines, specimens, and other material.

f. Ship study samples, as described in the SOW, to the DAIDS Nonhuman Primate Core Immunology and Virology Laboratory contractors at Duke University (Durham, NC), Tulane University (New Orleans, LA), and Duke University (Durham, NC). Assume monthly shipments of 100 vials containing 1 ml to each lab.

g. All shipment of virus and nonhuman primate-derived samples shall be shipped in compliance with International Air Transport Association (IATA) Dangerous Goods Regulations or with Department of Transportation (DOT) regulations. All shipping procedures, conditions, and containers shall be appropriate for biocontainment and preservation of the integrity of study materials.

2. Shipment/Transport of Nonhuman Primates

a. Coordinate the shipment/transport of nonhuman primates when any nonhuman primates housed in your facility need to be transferred to another SVEU contractor to undergo study. Shipping costs should not be budgeted for under Task Area 1 but should be budgeted for under the Task Order that ships the animals.

b. Shipment of nonhuman primates shall be made in accordance with International Air Transport Association (IATA) Dangerous Goods Regulations for shipment by air transportation, or with Department of Transportation (DOT) regulations for shipment by ground transportation (http://www.access.gpo.gov/nara/cfr/waisidx_99/49cfrv2_99.htm).

http://www.access.gpo.gov/nara/cfr/waisidx_99/49cfrv2_99.htm

Attachment 12, Additional Business Proposal Instructions 5

3. Facilities

a. Provide dedicated -80° freezer space and dedicated liquid nitrogen storage for storage of study materials. Assume 1 of each type of freezer.

b. Provide office and laboratory space appropriate for the conduct of the activities of the SOW.

4. Reporting

a. The Contractor shall provide monthly animal census reports and updates of project status, via telephone or e-mail, weekly or when requested by the COR.

b. The Contractor shall provide information on project status to SVEU personnel in

Task Area 1 as appropriate for inclusion in required Task Order Reports as described in the Reporting Requirements section of the Task Order.

5. Travel

a. Offerors should estimate the cost of one trip per year to NIH, Bethesda, MD, for two investigators for a two-day meeting with the COR and other NIAID staff.

b. The following general cost assumptions apply to travel:

1) Assume all airfare to be economy class.

2) Assume hotel and per diem at U.S. Government rates for the applicable city/location.

6. Transition Offerors should budget for the transfer of administrative and management responsibilities for nonhuman primates for Task Areas 2 and 3 from the predecessor SVEU contracts to the new SVEU Task Orders, including responsibility for animal documentation, clinical records, testing records, etc. Shipping costs will be borne by the predecessor contract(s).

7. Options

Options to Extend the Term: Offerors should propose budgets for the Base Year (Year 1), using the FTE level requested, and should also propose budgets for Options 1-6 to extend the Task Order term for Years 2 through 7.

Options for Increased Level of Effort: Offerors should propose budgets for Options 7-13 to increase the level of effort by 0.30 FTEs per year for Years 1 through 7.

A. Technical Cost Assumptions for Task Orders for Task Area 2: Maintenance of

Nonhuman Primates:

Immediately upon award of the Base contract, NIAID anticipates issuing a Task Order to each awardee for the Maintenance of Nonhuman Primates under Task Order 002-1. The Contractor(s) receiving these Task Order awards must be capable of initiating these Task Orders immediately upon award. In addition, immediately upon award of the Base contract, NIAID anticipates issuing one Task Order 002-2 to one awardee.

Attachment 12, Additional Business Proposal Instructions 6

Offerors must submit separate cost proposals for Task Order 002-1 and (if applicable) for Task Order 002-2.

1. Task Order 002-1, Care and Maintenance of an Average of 15 SPF Nonhuman

Primates per Year The Contractor shall propose a budget to provide care and maintenance of nonhuman primates at an AAALAC-accredited and OLAW-compliant ABSL2/3 facility that can accommodate an annual average of 15 nonhuman primates, awaiting assignment to a study plan.

a. The cost proposal should include costs associated with providing 0.27 FTEs/year.

b. The cost proposal should include costs to cover the per diem charges to house and provide care and maintenance for an average of 15 nonhuman primates per year.

Therefore, budgets should include per diem costs based on 15 nonhuman primates multiplied by 365 days multiplied by a set per diem rate per year.

c. The cost proposal should also include other animal-associated costs not included in the per diem charges.

d. Offerors should propose costs for testing to assure that acquired nonhuman primates are free of SIV, STLV, SRV, Herpes B, and TB.

e. The following level of effort shall be provided in support of this Task Order. The personnel categories are provided as an estimate and are not meant to be restrictive.

Offerors must provide the specified level of effort but may propose a different labor mix deemed most appropriate to carry out the Statement of Work.

Task Area 2, Task Orders for Maintenance of 15 Nonhuman Primates, during the period of performance of this Task Order, the Contractor shall provide 0.27 FTEs per year. It is estimated that the FTEs are constituted as specified below and will be expended approximately as follows:

Principal Investigator .01 Other Professional .05 Technical Support .21 Total .27

Options to Extend the Term: Offerors should propose separate budgets for the Base Year (Year 1), using the FTE level requested, and shall also propose budgets for Options 1-6 to extend the Task Order term for Years 2 through 7.

Options for Increased Level of Effort: Offerors should propose separate budgets for Options 7-27 for Increased Level of Effort to add maintenance of 5 nonhuman primates per year in an ABSL2/3 facility. The requirement will be for an additional

0.09 FTEs per year for Years 1-7. Options for Increased Level of Effort may be exercised up to three (3) times per year.

Attachment 12, Additional Business Proposal Instructions 7

2. Task Order 002-2, Maintenance of an Average of 30 SPF Nonhuman Primates/ year

The Contractor shall propose a budget to provide care and maintenance of nonhuman primates at an AAALAC-accredited and OLAW-compliant ABSL2 facility that can accommodate an annual average of 30 nonhuman primates, awaiting assignment to a study plan.

a. The cost proposal should include costs associated with providing 0.06 FTEs/year.

b. The cost proposal should include costs to cover the per diem charges to house and provide care and maintenance for an average of 30 nonhuman primates per year.

Therefore, budgets should be based on 30 NHPs multiplied by 365 days at a set per diem rate per year.

c. The cost proposal should also include other animal-associated costs not included in the per diem charges.

d. Offerors should propose costs for testing to assure that acquired nonhuman primates are free of SIV, STLV, SRV, Herpes B, and TB.

e. The level of effort to be provided in support of this Task Order follows. The personnel categories are provided as an estimate and are not meant to be restrictive. Offerors must provide the specified level of effort but may propose a different labor mix deemed most appropriate to carry out the Statement of Work.

f. Task Area 2, Task Orders for Maintenance of 30 Nonhuman Primates, during the period February 1, 2020 through January 31, 2021, the Contractor shall provide

0.06 FTEs per year. It is estimated that the labor FTEs are constituted as specified below and will be expended approximately as follows:

Other Professional .01 Technical Support .05 Total .06

Options to Extend the Term: Offerors should propose separate budgets for the Base Year (Year 1), using the FTE level requested, and shall also propose budgets for Options 1-6 to extend the Task Order term for Years 2 thru 7.

Options for Increased Level of Effort: Offerors should propose separate budgets for Options 7-27 for maintenance of 10 additional nonhuman primates per year in an ABSL2 facility. The requirement will be for an additional 0.02 FTEs per year for Years 1-7. Options for Increased Level of Effort may be exercised up to three (3) times each year.

B. Technical Cost Assumptions for Task Orders for Task Area 3: Conduct of Studies in

Nonhuman Primates

General budget information applicable to all studies to be conducted under the Task Area for the Conduct of Studies in Nonhuman Primates:

Attachment 12, Additional Business Proposal Instructions 8

1. The Task Orders that will be issued (at a time subsequent to award of the SVEU Base contract) under Task Area 3 for the Conduct of Studies in Nonhuman Primates will be nonseverable completion contracts for performance periods ranging from approximately 6 months to approximately 2 years. It is the Government’s intent to fund these Task Orders in full at the time of Task Order award. However, if a study is large/complex, including multiple steps that require evaluation and decisions prior to moving to the next phase, the Government may request cost proposals to be budgeted in phases. The various phases will be set up as Options allowing the Government to make a choice about whether to move to the next phase.

2. Offerors will be expected to budget for animal per diems for the care and maintenance of nonhuman primates that are under study. The animal per diems should be budgeted based on the number of nonhuman primates under study multiplied by a set per diem rate multiplied by the number of days the animals are expected to be under study.

3. The Contractor will be expected to budget for the shipping/transport of nonhuman primates at study end to other sites, as necessary.

C. SAMPLE TASK ORDER for Task Area 3: Conduct of Studies in Nonhuman

Primates: Virus Titration

Offerors must submit a separate cost proposal for this sample Task Order to allow the Government to evaluate cost reasonableness. While it is not anticipated that a Task Order to conduct a virus titration study will be issued upon award of the base contract, it is anticipated that it will be issued within the first few months of the contract, as virus stocks are prepared, and titrations are needed.

Offerors are instructed to submit a budget to provide the personnel, materials and supplies, equipment, appropriate animal facilities, Rhesus PBMC and other resources necessary to conduct the sample virus titration study as described in the Statement of Work.

1. Assume that 3 groups of 6 SPF Indian origin female Rhesus macaques 3 to 12 kg will be available and shipped from NIAID at no cost. You will arrange shipping of monkeys from Alice, Texas, to your facility. Assume that all animals will be transported and quarantined at your facility prior to the start of the study.

2. Prepare a budget based on the following assumptions:

a. Rhesus macaques, as sources for the PBMC upon which to expand the SIV, are already in your facility.

b. All shipping costs for titration animals will be borne by the supplier at no cost to this Task Order.

Attachment 12, Additional Business Proposal Instructions 9

c. Study Day 0 begins once quarantine (and acclimation to the study room) is completed. Include in your budget costs that cover the period from arrival to Study Day 0.

d. For simplicity, each group of 6 animals will be budgeted as a bloc.

o All animals are in ABSL2/3 for Study days 0-60.

o The first study cohort (N=6) will be euthanized on day 30 (after outcome of first exposure).

o 12 animals will continue during Study Days 30-120.

e. In the first stage, using the first group of 6 animals, conduct intravaginal challenges of three pairs of NHPs, exposing each pair of animals to a different dilution of the virus stock. The virus stock dilutions will be selected based on the in vitro titer of the stock. From the result of the infectivity of the three different doses, select two candidate dilution and conduct weekly vaginal challenges of six

(6) rhesus (Group 2) with dilution #1 and six (6) rhesus (Group 3) with dilution #2 for a total of eight (8) weeks. Follow the animals for 4 additional weeks to confirm infection, collecting weekly plasma samples to detect plasma virus RNA, determine the rate of virus acquisition at each dose and use the data to select the dilution for use in challenges of NHPs in vaccine studies.

f. The second and third study groups (N= 12) will be euthanized on Day 120.

g. Assume that animals will be bled weekly to obtain plasma for determination of virus load.

o Costs to expeditiously deliver the plasma samples to the NIAID

Nonhuman Primate Core Virology Laboratory (Duke University, Durham, NC) are your responsibility.

o Assume 4 plasma shipments during the 30-day study period for the first cohort and another 12 for the second set of 2 x 6 (12) NHPs.

h. Assume also that the first group will receive a single vaginal exposure.

i. Assume that the second and third groups will be exposed weekly for 8 weeks.

j. Also include costs for the in vitro expansion and TCID50 determinations.

k. The in-life phase will end at Study Day 180. For costing purposes only, assume that any remaining animals will be euthanized.

l. The Final Deliverable is the Study Report. Include in the total budget the cost to prepare and deliver this Report.

D. SAMPLE TASK ORDER for Task Area 3: Conduct of Studies in Nonhuman Primates: Conduct of a Vaccine Immunogenicity Study

Offerors must submit a separate cost proposal for this sample Task Order to allow the Government to evaluate cost reasonableness. While it is not anticipated that a Task Order to conduct a vaccine immunogenicity study will be issued upon award of the base contract, it is anticipated that one could be issued within the first few months of the base contract, as requests for SVEU-conducted studies are received by the Government and approved for performance.

Offerors are instructed to submit a budget to provide the personnel, materials and supplies, equipment, ABSL2/3 housing facilities, and other resources necessary to

Attachment 12, Additional Business Proposal Instructions 10 conduct the sample vaccine immunogenicity study as outlined in the table below and described in the SOW.

Assume that Statement of Work items have been completed, that the Study Plan has been developed and approved by the IACUC and COR, and that the Treatment and Sample Collection Schedule has been completed.

1. Assume that 12 SPF Indian origin Rhesus macaques of appropriate age and maturity and will be available from NIAID at no cost and that you will arrange shipping of monkeys from Alice, TX, to your facility and assume that all animals will be transported and quarantined at your facility prior to the start of the study. The proposed budget should not include costs for animal shipping, but should include costs for quarantine, and housing/care during the study period.

2. The table in the SOW outlines the proposed study design and the sample collection schedule, which is intended to serve as the basis for the development of the budget for this task.

3. Additional Cost Information

a. Serum is to be collected, labeled and frozen in 0.5 ml aliquots. Plasma samples, obtained as PBMCs are isolated, can be frozen in larger volumes (1-5 ml), as appropriate.

b. Blood is to be collected, processed to obtain PBMCs and/or serum at the collection times listed in the SOW. Blood is to be collected, and the PBMCs processed, and viably frozen in liquid nitrogen at concentrations appropriate for subsequent use in assays to assess cellular immune responses to the SIV vaccines.

(Budget for the processing and viable freezing of PBMCs at the time points indicated in the SOW Study Sample Collection Table.)

c. Budget for the conduct of ELISA assays (all time points), Pepscan assays (pre-immunization and 2 time points), B cell ELISPOT assays pre-immunization and 2 time points.

d. Mucosal secretions and saliva are to be collected and frozen for assessment of antibody and cytokine/chemokine responses to the vaccine. (Budget for the collection and processing of samples at the time points indicated in the SOW Study Sample Collection Table.)

e. Tissue samples, including jejunal biopsies, lymph nodes, and bone marrow aspirates and BAL are to be processed and lymphocytes are to be viably frozen (or assayed fresh, when possible) for FACS-based assays and frozen in RNA-later for microarray or other transcriptomic assays. (Budget for the collection and processing of samples at the time points indicated in the SOW Study Sample Collection Table.)

Attachment 12, Additional Business Proposal Instructions 11

f. Frozen sera and mucosal secretions are to be shipped to the NIAID Nonhuman Primate Humoral Immunology Laboratory (Duke University, Durham, NC) for assay. (Budget for 5 shipments)

g. When requested by the COR, whole blood samples may be shipped overnight at controlled ambient temperature to Tulane University (New Orleans, LA) for cellular immunology assays (Budget for 12 shipments).

h. Paxgene and RNA-later samples are to be stored frozen, and selected samples are to be shipped to the NIAID Nonhuman Primate Genomics Laboratory at the University of Washington, Seattle, WA for transcriptomic (microarray) assays.

(Budget for 2 shipments)

i. FACS-based assessment of PBMCs for T and B cell immune responses are to be conducted on a subset of PBMC samples from the study times indicated in the Study Table. Offerors should propose to purchase antibodies for the assays.

(Budget for the conduct of assays on 10 samples collected as described in the

SOW.)

j. FACS-based assessment of mucosal T and B cell immune responses from mucosal samples, lymph nodes, bone marrow, etc., are to be conducted on samples obtained at the 7 times indicated in the Study Table. Offeror should propose to purchase antibodies for the assays.

k. Offerors’ cost proposals should include costs for assays to monitor the clinical health of the nonhuman primates.

l. Cost proposals should include the cost of sample storage.

m. For costing purposes, assume that all animals will be euthanized at study end and that a necropsy will be conducted on all the animals to obtain mucosal and lymphoid tissues for further analysis. Include the cost of biopsies, the collection and processing of terminal samples: blood, lymph nodes, duodenum and other mucosal tissues, bone marrow, and limited other tissues. Also include the cost of the conduct of a final set of FACS-based assays on lymph and mucosal samples.

n. The Final Deliverable is the Study Report. Include in the total budget the cost to

E. SAMPLE TASK ORDER for Task Area 3: Conduct of Studies in Nonhuman

Primates: Conduct of a Vaccine Efficacy Study

Offerors must submit a separate cost proposal for this sample Task Order to allow the Government to evaluate cost reasonableness. While it is not anticipated that a Task Order to conduct a vaccine efficacy study will be issued upon award of the base contract, it is anticipated that it will be issued within the first few months of the base contract, as

Attachment 12, Additional Business Proposal Instructions 12 requests for SVEU-conducted studies are received by the Government and approved for performance.

Offerors are instructed to submit a budget to provide the personnel, materials and supplies, equipment, ABSL2/3 housing facilities, and other resources necessary to conduct the sample vaccine efficacy as outlined in the tables in the SOW.

Assume that Statement of Work tasks have been completed, that the Study Plan has been developed and approved by the IACUC and COR, and that the Treatment and Sample Collection Schedule (below) is part of the Study Plan.

Assume that 30 SPF Indian origin Rhesus macaques 3 to 12 kg will be available from NIAID at no cost and that you will arrange shipping of monkeys from Alice, TX, to your facility and assume that all animals will be transported and quarantined at your facility prior to the start of the study. The proposed budget should not include costs for animal shipping, but should include costs for quarantine, and housing/care during the study period.

The tables in the SOW, outline the proposed study design, which is intended to serve as the basis for the development of the budget for this task. The activities to be conducted are described in the SOW.

Additional Cost Information

1. Serum is to be collected, labeled and frozen in 0.5 ml aliquots. Plasma samples, obtained as PBMCs are isolated, can be frozen in larger volumes (1-5 ml), as appropriate.

2. Blood is to be collected, processed to obtain PBMCs and/or plasma/serum at the collection times listed in the SOW. Processed PBMCs are to be viably frozen in liquid nitrogen at concentrations appropriate for subsequent use in assays to assess cellular immune responses to the SIV vaccines. (Budget for the processing and viable freezing of PBMCs at 14 times points, 30 nonhuman primates, during the immunization phase and for 3 time points post infection.)

3. Rectal secretions are to be collected and frozen for assessment of antibody responses to the vaccines. (Budget for the processing of 14 time points, 30 nonhuman primates during the immunization phase, and for two time points post infection.)

4. Tissue samples, including rectal biopsies, lymph nodes, and bone marrow aspirates are to be processed and lymphocytes are to be viably frozen (or assayed fresh, when possible) (Budget for the processing of lymph nodes, bone marrow, and rectal biopsies each, for 4 time points, 30 nonhuman primates.)

5. A portion of the rectal biopsies shall also be used for microarrays. Budget for reagents necessary for this (RNA later etc.) at four time points, 30 nonhuman

Attachment 12, Additional Business Proposal Instructions 13 primates. These samples shall be shipped together with the Paxgene and rectal swabs.

6. Frozen sera and mucosal secretions are shipped to the NIAID Nonhuman Primate

Humoral Immunology Laboratory (Duke University, Durham, NC) for assay.

(Budget for 5 shipments)

7. Paxgene samples are to be stored frozen, and selected samples are to be shipped to the NIAID Nonhuman Primate Genomics Laboratory at the University of Washington, Seattle, WA for transcriptomic (microarray) assays. (Budget for 2 shipments).

8. Rectal Swabs for microbiome analyses are to be processed and stored as indicated in

SOP (to be provided) and selected samples are to be shipped to the NIAID Nonhuman Primate Genomics Laboratory at the University of Washington, Seattle, WA for transcriptomic (microarray) assays. Budget for one shipment.

9. FACS-based assessment of PBMCs for T and B cell immune responses are to be conducted on samples from the study times indicated in the Study Table. For purposes of this cost proposal, it is only necessary to assess responses to HIV Env in the 20 nonhuman primates receiving the vaccines. Offerors should propose to purchase antibodies for the assays. (Budget for T-cell FACS on samples at 14 time points; B-cell FACS and B cell ELISPOT assays at 14 time points).

10. FACS-based assessment of mucosal T and B cell immune responses from mucosal samples, lymph nodes, bone marrow, etc., are to be conducted on samples obtained at the times indicated in the Study Table. For purposes of this cost proposal, it is only necessary to assess responses to HIV Env in the 20 nonhuman primates receiving the vaccines. Offeror should propose to purchase antibodies for the assays.

11. Plasma collected for virus load determination shall be frozen in 1.0 ml aliquots and stored until shipped to the NIAID Nonhuman Primate Virology Laboratory at Duke University, Durham, N.C. for assessment. Budget for 11 weekly shipments (after each of 10 challenges) plus monthly shipments during the 24-week post infection follow-up period.

12. Cost proposals should include the cost of sample storage.

13. For costing purposes, assume that all animals shall be euthanized at study end.

14. The Final Deliverable is the Study Report. Include in the total budget the cost to

NOTE: The in-life portion of this study (immunization and virus challenge) is estimated to be 90 weeks after quarantine time period. A period of 6 months following the end of the virus challenge period is to be used to complete the conduct

Attachment 12, Additional Business Proposal Instructions 14 of assays for the study and for the preparation of study reports (including entry of the study information and data into the SVEU Vaccine Study Database.

F. Technical Cost Assumptions for Task Order for Task Area 4: Operation of a

Nonhuman Primate Breeding Colony

Contractors submitting Technical Proposals for Task Area 4 shall submit a separate cost proposal to provide care and maintenance of SPF nonhuman primates at an AAALAC-accredited and OLAW-compliant outdoor small-group housing facility that can accommodate 500 nonhuman primates currently owned by the Government and currently housed at a facility owned and managed by Covance Research Products, Inc.

under a subcontract with the current SVEU contractor. The cost proposal should include:

1. The level of effort to be provided in support of the Breeding Colony is 0.50 FTEs and is constituted as follows. The personnel categories are provided as an estimate and are not meant to be restrictive. Offerors must provide the specified total level of effort but may propose a different labor mix as deemed most appropriate to carry out the proposed Statement of Work.

Principal Investigator 0.17 Project Manager 0.17 Veterinarian 0.16 Total 0.50

2. Costs to cover the per diem charges to house and care for 500 nonhuman primates for each performance year. Offspring, 0-6 months, are not included in the 500 nonhuman primate census.

3. Cost associated with a breeding program to generate 60-100 SPF nonhuman primates per year.

4. Other animal-associated costs not included in per diem charges.

5. Costs associated with providing monthly animal census reports and updates of project status, via telephone or e-mail, weekly or when requested by the COR.

6. Options to Extend the Term: Offerors should propose budgets for the Base Year (Year 1), using the FTE level requested above, and shall also propose budgets for Options 1-6 to extend the Task Order term for Years 2 through 7.

7. Options for Increased Level of Effort: Offerors should propose separate budgets for Options 7-13 to provide maintenance of an additional 50 nonhuman primates per year. The requirement will be for an additional 0.05 FTEs per year for Years 1-7.

Options for Increased Level of Effort may be exercised one (1) time per year.