Statment of Work NIAID NOI 22 2115314.pdf

STATEMENT OF WORK

Synthesis of SARS-CoV-2 Variant Genes

I. Background

The National Institute of Allergy and Infectious Diseases (NIAID) supports a variety of preclinical research resources and services to promote the discovery and development of new medical countermeasures for prevention and treatment of infectious diseases.

NIAID is involved in efforts across the USG to respond to the COVID-19 pandemic by supporting the development of therapeutics and vaccines targeting SARS-CoV-2 and monitoring the effectiveness of these new countermeasures as they are deployed in the clinic. Ongoing global surveillance of SARS-CoV-2 viral sequences and rapid assessments of the impact of emerging changes in virus sequences on efficacy of vaccines and therapeutics are critical. The accumulation of mutations in the Spike (S) protein compared to the sequence used to develop medical countermeasures currently in clinical development raises concerns about their potential to reduce virus susceptibility to neutralization by antibodies. Neutralizing antibodies (nAbs) are believed to be an important component of protective immunity. The nAbs block virus infection by preventing S protein binding to the cellular receptor or by interfering with S protein conformational changes needed to mediate virus entry into cells. Most COVID-19 vaccines under development aim to elicit neutralizing antibodies. Similarly, neutralizing antibodies are being developed for therapeutic and preventive indications. A better understanding of the effect of the substitutions in the S protein on virus susceptibility to neutralizing antibodies will inform strategies to develop vaccines and antibodies for clinical use. The large number of substitutions in S proteins among SARS CoV-2 isolates from across the globe requires high-throughput assays to analyze how variant S proteins affect virus neutralization and S protein function. A foundational requirement to facilitate these assays is the capability to rapidly synthesize and clone variant S genes as they are identified through global surveillance efforts. Therefore, NIAID urgently requires access to a commercial services vendor that provides rapid and reliable synthesis and cloning of selected priority variants of SARS-CoV-2 S genes for use in assays to test the neutralization potency of antibody therapeutics candidates, convalescent plasma, and sera or plasma from vaccine recipients.

II. Scope

The Contractor shall provide the following commercial services as requested by the NIAID Contracting Officer’s Representative (COR): Gene synthesis (<=4 kilobase pairs, kb), Mutagenesis (up to 5 mutations in 4 kb gene), Subcloning into specified plasmid (4 ug delivered), and Plasmid preparation (100 ug delivered). “Rush” or “Express” services are required to obtain the most rapid turn-around time available to meet the urgency required to support the COVID response.

III. Contractor Requirements:

The Contractor shall be required to furnish all the necessary services, qualified personnel, material, equipment, and facilities as needed to perform the following tasks:

A. Gene Synthesis. The Contractor shall rapidly synthesize 150 genes of up to 4 kb in length, as requested by the NIAID Contracting Officer’s Representative (COR) to support the COVID response. Most typically, the requests shall be for specific variants of the SARS-CoV-2 Spike gene (3847 bp in length). The “Rush” gene service shall be used for these requests in order to access the most rapid turn-around time (see F below).

B. Mutagenesis. The Contractor shall rapidly create 150 new variant genes, as requested by NIAID COR to support the COVID response, using mutagenesis of genes from existing plasmids. The mutagenesis service shall accommodate 1- 5 specific mutations to the sequence of genes up to 4 kb. The “Rush” service shall be used for these requests in order to access the most rapid turn-around time (see F below).

C. Express Cloning. The Contractor shall perform 250 Express Cloning services, as requested by the NIAID COR to support the COVID response, with newly synthesized genes (described in section A above). The vector used for this cloning typically shall be pcDNA3.1(+). The “Express” cloning service shall be used for these requests in order to access the most rapid turn-around time (see F below).

D. Plasmid Preparation. The Contractor shall perform a total of up to 425 Rush

Plasmid Preparation services to generate 100 ug purified plasmid in high-copy number, as requested by the NIAID COR to support the COVID response. In addition to plasmid preparation requests that are combined with synthesis and cloning (A and B above) or mutagenesis (C above) requests, plasmid preparation services shall be requested for genes previously synthesized and cloned, for the purpose of supplying priority plasmids to multiple testing sites, as requested by the NIAID COR. Shipping to a single site, as specified by NIAID COR, shall be included as part of each plasmid preparation services. Multiple plasmid preparations shall be combined into a single order to allow for shipment to multiple sites, as needed and as specified by NIAID

COR.

E. The following turn-around times (TAT) shall be met for the above-described services

(or combination of services) from request submitted to receipt of plasmids:

i. Gene Synthesis, Express Cloning and Plasmid Preparation for delivery of a minimum of 100 ug plasmid within 3 weeks.

ii. Mutagenesis and Plasmid Preparation for delivery of 100 ug plasmid within 2 weeks.

iii. Plasmid Preparation from existing plasmid for delivery of 100 ug plasmid within 1 week.

iv. On a very limited basis (<5), orders for very high-priority constructs may be placed where more rapid turn-around times will be required. These high priority orders will be clearly communicated with the Contractor at the time of ordering and streamlined process will be used to achieve the most rapid turn-around times possible, while accepting an increased risk of failure.

F. Requests shall be submitted to the Contractor by the NIAID COR (or designate) on an ad hoc basis throughout the period of performance, until the total number of services for each type (as described in A-D above) are committed.

G. The Contractor shall provide the NIAID COR with an accounting of the number of requests submitted and delivered, along with timelines, at least monthly by email.

IV. Period of Performance:

The estimate total period of performance for this requirement is one (1) year from date and acceptance of award.