36C24E23Q0120.docx

Special Notice Special Notice

GENERAL INFORMATION

Regional Procurement Office East Building 32 Suite 1A1111 1010 Delafield Road Pittsburgh PA 15215-1802

POINT OF CONTACT*

Contracting Officer Michael Haydo michael.haydo@va.gov

ADDITIONAL INFORMATION

AGENCY’S URL

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AGENCY CONTACT’S EMAIL ADDRESS

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DESCRIPTION

The Veteran’s Administration (VA) Office of Research and Development, Regional Procurement Office – East in Pittsburgh, PA intends to negotiate on a sole source basis with The University of Pennsylvania based in Philadelphia, PA on behalf of the James J. Peters Murphy Medical Center in Bronx, NY. The requirement is to provide research assistance for planned VA medical studies.

Title of project: Vaccine targeting HIV sites of vulnerability.

Background and Description

The project’s purpose is to produce the lead HIV vaccine immunogen V1V2/A244-2J9C as a research-grade mRNA vaccine and test its optimized construct in the rabbit model in order to pave the way toward a human phase I clinical trial in the future. The V1V2/A244-2J9C mRNA vaccine will be the first of their kind to move toward clinical trials. An effective vaccine to prevent HIV infection and/or disease is an essential portion of the Strategic National Vaccine Plan of the Departments of Health and Human Services and Veterans Affairs.

Effective HIV vaccines are not yet available. Of the phase 2b/3 vaccine trials, only the Thai RV144 trial showed efficacy (31%, p=0.04), and high levels of antibodies (Abs) against the V1V2 domain of HIV envelope (Env) were found to be the only primary immune correlate of reduced virus acquisition. Studies of vaccines in SIV or SHIV-challenged monkeys have since recapitulated these findings. To improve upon the RV144 vaccine, we have designed V1V2-targeted vaccine candidates and identified the most immunogenic: V1V2/A244-2J9C, a protein with V1V2 of CRF_01.AE strain A244 spliced into a bacterial trimeric protein scaffold, 2J9C.

Scope and Methodology

Three specific objectives will be performed by the laboratory at the University of Pennsylvania to help achieve the overall goal of the project proposed in the VA Merit Review grant. The first objective is to generate 3 different V1V2/A244-2J9C-expressing DNA plasmids, produce the respective mRNA products, and test each mRNA product in vitro for protein expression. The second is to produce lipid nanoparticles that encapsulate each of the mRNA products (LNP-mRNA) and test them individually to immunize mice. The third is to produce the optimal LNP-mRNA vaccine for use in rabbit immunization; this LNP-mRNA vaccine will be sent to the lab at the James J. Peters VA Medical Center and rabbit immunization will be performed.

Tasks and Associated Deliverables

The VA will provide the following items for initiation of the project:

· Sequence details of V1V2/A244-2J9C

· A panel of monoclonal antibodies against V1V2

· Protein antigens for testing mouse serum samples

The University of Pennsylvania will perform the following tasks with the specified deliverables for each task.

1) Production of three different DNA plasmids expressing V1V2/A244-2J9C and mRNA products from the V1V2/A244-2J9C plasmids and testing protein expression in 293T cells using the V1V2-specific monoclonal antibody panel.

2) Production of LNP-mRNA vaccines for testing in mice and analysis of mouse sera for antibodies against V1V2.

3) Production of the best LNP-mRNA vaccine for testing in rabbits.

Deliverables:

· DNA sequences and in vitro protein expression data for the 3 constructs tested.

· Data for the mouse antibody responses elicited to V1V2 after immunization.

· The best LNP-mRNA vaccine for testing in rabbits (5 rabbits per group, 4 doses).

The requirement will take place at a VA facility in Bronx, NY. The sole source is pursuant to FAR 6.302-1 Only One Responsible Source and No Other Supplies or Services Will Satisfy Agency Requirements. This notice of intent is not a request for competitive proposals, however; any responsible source who believes it is capable of meeting the requirement may submit a capability statement and supporting documentation to the contracting office no later than Thursday, April 20, 2023, (10:00 AM, EST). Interest/capability statements may be sent to Michael Haydo at Michael.haydo@va.gov. No telephone responses will be accepted. A determination not to compete the proposed requirement based upon the responses to this notice is solely within the discretion of the Government.

Special Notice