NEW YORK – Philadelphia-based PCR instrument and assay developer Biomeme and Kansas City, Missouri-based contract research organization MRIGlobal have recently validated a SARS-CoV-2 variant surveillance system.
The lyophilized assay can detect 12 mutations to distinguish five major variants of concern — Alpha, Beta, Gamma, Delta, and Omicron — on high-throughput PCR systems as well as on Biomeme's portable PCR platform, making them amenable to cash-strapped labs or low-resource settings. The team has also validated an expanded pentaplex assay that can detect all sublineages of the Omicron variant.
The project was funded by the US Defense Biological Product Assurance Office (DBPAO) and the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND). Biomeme and MRIGlobal also developed and validated the system in partnership with teams at the US Naval Health Research Center, Integrated DNA Technologies, and consulting group Logistics Management Institute.
Jennifer Stone, principal scientist at MRIGlobal, said in an interview that she worked closely with DBPAO to design a study and bring in collaborators.
MRIGlobal and Biomeme have also worked together in the past, and readily teamed up to design and optimize the different SARS-CoV-2 assays. MRIGlobal then validated the system in house before sending it to the Naval Health Research Center to run high-throughput clinical specimen testing.
Whole-genome sequencing remains the preferred method for SARS-CoV-2 variant surveillance, but it is notoriously expensive and time consuming.
On top of that, Stone said, PCR can be several orders of magnitude more sensitive than sequencing, making it a good approach in cases where the viral titer is low.
Digital PCR is also a favored approach for variant testing, but the precise quantitation it engenders may not always be required, Stone said. Furthermore, qPCR has the advantage of being easily multiplexed using standard equipment, which can bring costs down as well, Stone said.
In a study posted to medRxiv last month, the team showed that the genotyping tests had high sensitivity and specificity in clinical samples.
Biomeme's Franklin instrument is a portable, battery operated PCR system that can be deployed in the field with a minimal footprint.
The firm also provides multiple assay formats, including lyophilized, room-temperature stable three-well "Go-Strips," and 96-well "Go-Plates" that can be used in high-throughput instruments with multiplex capabilities.
Stone said that the DBPAO is now providing the system to different US Department of Defense groups, including both clinical and wastewater testing.
As a CRO, MRIGlobal aims to help groups like Biomeme come up with products that are commercially marketable, Stone said. Although CROs aren't always able to publicly disclose the work they do for companies or the US government, one recent notable exception was a project with C2Sense. MRIGlobal was able to show that firm's low-cost, consumer-friendly lateral flow immunoassay reader, called the Halo, yielded comparable results to six commercially available assays.
The importance of variant testing
A lyophilized SARS-CoV-2 assay from Biomeme has previously received Emergency Use Authorization, but the SARS-CoV-2 variant panel is intended for research use only today. Whether and how it will be further commercialized by the collaborators remains to be determined.
"If there is interest from groups outside of DoD, at that point we will have a conversation with Biomeme and DBPAO about ramping up production to meet the needs," Stone said.
Jesse vanWestrienen, a Biomeme cofounder and executive VP of products, said in an email that Biomeme was inspired to contribute the Franklin and the firm's assay development expertise to the project because of a clear need for a rapid, low-cost alternative to sequencing for variant detection.
"Not only could these assays be used to correlate to variants of concern and give clinicians more timely information that could inform antibody treatment decisions, but they could also be used to triage samples to be sent for full genome sequencing," vanWestrienen said.
The approach has precedent. Using a similar portable PCR system — the Mic from Bio Molecular Systems — David Perlin and his team have been characterizing the variant from every SARS-CoV-2 positive patient at Hackensack Meridian Health System using assays they developed in house.
Perlin, who is CSO and senior VP at HMHS' Center for Discovery and Innovation in New Jersey, said that the approach used in the medRxiv study is essentially identical to the one his lab uses. For this work, a portable system is particularly "valuable for clinics who may have a high volume of patients and where VOC identification drives potential therapeutic options," he noted.
In the HMHS lab, which genotypes the bulk of COVID cases in the state of New Jersey, the BA.4/5 variant currently represents about 95 percent of the viruses within the community, Perlin said, and this knowledge in turn drives therapy choice.
But, vaccine boosters covering BA.4/5 and new antiviral medications on the horizon may also place a strong selection pressure on existing virus pools, "that can, and likely will, result in new variants," he noted.
With the next variant around the corner, "a robust surveillance program that can detect changes in the virus population is important for public health measures," Perlin said.
Joe Tumolo, Biomeme's VP of sales and strategic partnerships, noted as well that a One Health approach may be particularly useful for future SARS-CoV-2 surveillance.
"Domestic cats have spread SARS-CoV-2 to feral cats, which likely spread the virus to white-tail deer," he said. "So the virus now has a reservoir in which to mutate."
From Biomeme's perspective, it is essential to ramp up surveillance of SARS-CoV-2 variants and key mutations "within wildlife, wastewater, and indoor air systems," Tumolo said.
To this end, "deploying something like a SARS-CoV-2 assay in a pre-mixed, shelf-stable format dramatically lowers the cost and complexity of shipping logistics, reduces the risk of contamination, and improves quality control across sites," he also said.
Biomeme's field thermocyclers can also wirelessly sync GPS-tagged data to the Biomeme Cloud, "enabling remote backup, real-time data analysis, and quality control, as well as integration with third-party lab information management systems or epidemiological databases through our Web API," Tumolo said.
Biomeme has deployed the Franklin system across its wholly owned CLIA high-complexity, CAP-accredited nationwide lab network, called One Health Laboratories. The systems integrate with both LIS and state reporting systems, and quality teams can also remotely analyze data by technician, reagent lot, and thermocycler, Tumolo said.
Users of these systems can therefore "span a variety of drastically different verticals," he said, adding, "That is the beauty of the platform."