Attachment_5_-_SOW_edited_for_posting.docx

STATEMENT OF WORK

52 Week Service Contract for Rhesus Macaques Blood, bone marrow and tissues with HIV-1 envelopes POP 52 weeks from start date

1) BACKGROUND INFORMATION

The Laboratory of Immunoregulation (LIR) focuses research efforts on the development of novel strategies for the prevention and treatment of HIV-1/AIDS. The scientific basis for the rational design of new protective vaccine strategies for the prevention of HIV transmission depends on the development of novel immunogens capable of inducing the production of broad and potent neutralizing antibodies (bNAbs). Despite considerable efforts, no HIV vaccine strategy so far has succeeded in eliciting bNAbs in pre-clinical studies. LIR recently designed a novel set of HIV-1 vaccine immunogens based on stabilized HIV-1 envelope (Env) trimers, which display a bona fide “native” prefusion conformation selectively recognized by bNAbs, but not by non-neutralizing antibodies. This new vaccine concept has already been tested in rabbits (partly through OAR support) and in coordination with Bioqual, showing its ability–for the first time–to elicit the production of cross-clade, tier-2/-3 bNAbs against HIV-1 strains with different phenotypic and genotypic characteristics. The goal of the present project is to follow up this initial success with the assessment of the immunogenicity and protective efficacy of these new vaccine immunogens in nonhuman primates (NHP). Thus, the LIR is requesting a contract for the collection of Rhesus Macaques Blood, bone marrow, and tissue with HIV-1 envelopes.

2) SCOPE

This service contract is necessary to collect the blood, bone marrow, and tissue sample with HIV-1 envelopes that are needed to assist in determining the success of new vaccines within LIR.

3) Objectives Collect Rhesus Macaques Blood, bone marrow, and tissue with HIV-1 envelopes by following the outlined schedule below.

4) Tasks The Contractor shall:

· The Contractor shall provide Animal Care and Usage Committee permission for the study.

· The Contractor shall provide veterinarian supervision and intervention in case of medical issues related or unrelated to the study protocol.

· Supply Animals (qty 15 rhesus macaques, female, sexually mature, negative for Mamu A01, B08 and B17);

· Administer immunizations by intramuscular injections with or without in vivo electroporation; (per schedule)

· Perform blood draws and bone marrow aspirations; (per schedule)

· Administer virus inoculations (repeated low-dose by vaginal application) (per schedule)

· Perform euthanasia for study termination – Necropsy for tissue collection (per schedule)

· Schedule:

Week 0. RNA prime 1 (400ug/animal, i.m.)

Week 4. RNA prime 2 (400ug/animal, i.m.) + Autologous protein boost 1(200ug/animal+Adjuplex, i.m. at different muscle site from DNA) Week 12. Autologous protein boost 2 (200ug/animal+Adjuplex, i.m.)

Week 16. Heterologous DNA prime 1 (1000ug x 3 per animal, i.m., with electroporation) Week 20. Heterologous DNA prime 2 (1000ug x 3 per animal, i.m., with electroporation) +Heterologous protein boost 1 (200ug x 3 per animal+Adjuplex, i.m.)

Week 24. Heterologous protein boost 2 (200ug x 3 per animal+Adjuplex, i.m.)

Week 32. Heterologous protein boost 3 (200ug x 3 per animal+Adjuplex, i.m.)

Week 36-41. Repeated low-dose mucosal SHIV inoculations, once per week (64 infectiousdoses, intravaginal).

Week 52. Study termination and necropsy.

5) Delivery The Contractor shall be responsible for the timely execution of the planned study and for the prompt communication of any emerging issues that may prevent or delay this execution.

6) Government Furnished Materials The Government (LIR) will provide all the immunogens (DNA and protein).

7) Security

NA

8) Place of Performance Rockville, MD 20850

9) INSPECTION

All work will be inspected and approved by Paolo Lusso, Senior Investigator in the Laboratory of Immunoregulation at National Institutes of Health or Huiyi Miao, staff scientist in the Laboratory of Immunoregulation at the completion of the job. All work will be completed in accordance with industry standards.

FAR Part 52.212-4