Tools to Streamline Infectious Disease Workflows

The COVID-19 pandemic has highlighted the importance of infectious disease research and its close relationship with public health. In a global effort to stem the waves of coronavirus infections and deaths, the furious storm of pandemic-related research revealed a silver lining of advanced technologies that are now available to streamline workflows in infectious disease labs the world over. This article looks at technologies and tools that are helping to accelerate workflows and advance discoveries in infectious disease research.

Automation and multiplexing

As in many fields, reducing bottlenecks using automated solutions can have a big impact on workflow. “Automation is being used more frequently in today’s laboratories as researchers strive to simplify their technologies, reduce the chance for operator error, and also alleviate workforce shortages,” says Sherry Dunbar, Senior Director of Global Scientific Affairs at Luminex. In addition, automation coupled with multiplexing is increasing workflow more than ever. Luminex’s xMAP Technology, for example, can measure up to 500 analytes in a single reaction, and Luminex’s high-throughput xMAP analyzers, the FLEXMAP 3D and xMAP INTELLIFLEX, can be connected to plate-handling systems for automation.

Preconfigured assay panels can also save time in assay development, screening, and epidemiological research. “Most researchers are under pressure to do more with less,” says Dunbar. “Being able to test for multiple targets simultaneously in a multiplexed panel saves time and cost, as well as reduces the amount of sample required.” Luminex’s assay panels, for example the xTAG GPP and NxTAG RPP, allow researchers to test for the most common pathogens causing gastrointestinal and respiratory infections, respectively.

Andy Lane, Commercial Director at The Native Antigen Company, observes that multiplex testing to investigate pathogenic targets is becoming more widespread. Traditionally, a patient’s symptoms lead to testing for the most likely infection, and then subsequently the next most likely. However, this approach can lead to delays and ultimately worse patient outcomes, with increased costs of multiple tests. Multiplex testing allows researchers to look for multiple markers of existing or previous infections, simultaneously. “This not only provides faster results, but a greater degree of certainty with regards to the infecting pathogen,” says Lane. “A common diagnostic example is testing for several respiratory viruses together—often SARS-CoV-2, influenza A and B, and respiratory syncytial virus.”

In the lab, more multiplex testing means more multiplex-enabled methods. “For immunoassays, this is increasingly taking the form of bead-based technologies and mass spectrometry,” says Lane. “For molecular assays, technologies such as microarrays, next-generation sequencing, and new forms of PCR, are proving to be better.”

Antibody neutralization

Among his customers, Lane notes that a major area of research is assessing the functionality and dynamics of antibodies in disease states, in particular neutralizing antibodies. Normally, the neutralizing ability of an antibody is evaluated by testing the effect of patient sera on viral infectivity in cell culture assays. But such experiments require specialized training and can take up to a week.

Instead, alternative immunoassay formats have been developed to measure indicators of neutralization, using methods that are both faster and cell-free. “For example, in vitro assays can be developed to measure the competitive interactions between viral antigens, their target receptor, and neutralizing antibodies,” says Lane. “Whether patient-derived or monoclonal, different antibodies at different titers can be evaluated in this way to assess neutralizing ability as a means of understanding host protection from natural or vaccine-induced immunity, as well as identifying therapeutic candidates.” The Native Antigen Company offers a range of such immunoassay reagents, particularly for SARS-CoV-2, as well as other viral and bacterial pathogens.

NGS and nucleic acid synthesis

NGS has become a critical tool for infectious disease workflows, allowing faster viral sequencing and vaccine development. Sylvain Gariel, Co-founder and COO at DNA Script, believes that NGS will be critical to detecting and combating the next pandemic in the earliest days, when it’s easier to stop. “The wide adoption of NGS will be critical for viral detection and surveillance, for monitoring its evolution and mutations,” he says, also predicting that the combination of NGS and single-cell techniques will be powerful for treating patients with severe disease. “Single-cell sequencing can help us understand the immune system and how a virus [like SARS-CoV-2] is interacting with a patient’s lungs,” he notes. “This will be a critical tool in understanding severe reactions such as cytokine storms in some patients.”

DNA Script offers the benchtop SYNTAX System, which uses an enzyme-based process to synthesize oligonucleotides within several hours, accelerating infectious disease workflows by reducing the time required to obtain nucleic acids. Most labs outsource this step, but waiting for the arrival of these important reagents can cause delays of days or weeks (even when not in the middle of a pandemic). “We want to enable our clients to be autonomous and get access to the nucleic acids they need in a few hours instead of a few days or weeks,” says Gariel.

mRNA-based vaccines

The technology behind the successful development of mRNA vaccines is also likely to accelerate infectious disease research. For example, BioNTech is developing a vaccine for malaria with the same mRNA technology used in its successful Pfizer-BioNTech coronavirus vaccine, with clinical tests planned by the end of 2022. The University of Oxford’s Jenner Institute is also working on a non-mRNA-based malaria vaccine. The only malaria vaccine currently available today, Mosquirix from GlaxoSmithKline, does not reliably reach the 75% efficacy goal set by the World Health Organization.

Besides being an important public health tool, vaccines also comprise a valuable asset for national defense—especially when they can be created rapidly. DNA Script is working with multiple partners to develop tools for detecting and responding to emerging biothreats. The SYNTAX System will allow the French Department of Defense to manufacture their own primers and probes without outsourcing. In addition, Moderna and GE Research have partnered with DNA Script to develop mobile, rapid production of mRNA-based vaccines and therapeutics, as part of the U.S.’s Defense Advanced Research Projects Agency’s (DARPA) Nucleic Acids On-Demand World-Wide (NOW) Program. “The first step is to make short pieces of DNA, and then assemble them into larger pieces that might become a plasmid for a DNA vaccine, or could go through an individual transcription step to become an mRNA molecule for an mRNA vaccine,” says Gariel. “We’re also developing multiple different biochemistries that we hope will enable customers to make long RNA molecules more efficiently than the existing chemistry.”

In contrast to the agents of infection, host cells may also shed new light on the diagnosis and treatment of infectious diseases. “Another exciting area of infectious diseases research is understanding the role of host proteins and host protein networks in the pathogenicity of microorganisms,” says Dunbar. “This research could identify host protein biomarkers as early indicators of infection and the class of microorganism responsible, as well as detect new targets for therapeutics.” Approaching infectious diseases from multiple angles will give us our best chance at defeating infectious agents.