[LUM#13] Spike, the Spy in the Service of Screening
What if the solution to the ever-growing lines outside testing centers could be summed up in one word: SPIKE? Five letters that sound like a code name for a specific protein in the virus that could form the basis of a new, faster and more effective.
PCR or serological test? Nasopharyngeal, blood, or saliva sample? Since the start of the pandemic, testing has become a part of our lives, and with it comes a host of questions: wait times, reliability, discomfort… “The tests used today are not optimal; we are working on new solutions that would allow us not only to increase testing capacity but also to improve their sensitivity and specificity,” explains Christophe Hirtz, a researcher at the Laboratory of Clinical Biochemistry and Proteomics*.
Spike, a specific protein
Unlike PCR tests —which stand for Polymerase Chain Reaction—that aim to detect the presence of the virus’s genome, blood or saliva tests known as “ELISA” detect specific proteins found in large quantities on the virus’s envelope. “One of these, which we call the spike protein, is of particular interest to us because it has a sequence specific to the virus and is crucial for its entry into the cell. If we find this sequence, it means we are dealing with SARS-CoV-2. There’s no mistaking it,” the researcher continues.
To detect this spike protein, Christophe Hirtz and his team use mass spectrometry—an analytical tool that identifies molecules based on their mass and characterizes their chemical structure. “Mass spectrometry will allow us to characterize the protein but also to understand the virus’s antigenicity—in other words, how our immune system will recognize the virus and trigger the right antibodies.”
Identifying Spike using antibodies
In fact, when a virus enters our body, our immune system identifies a protein that is characteristic of that virus—in this case, the Spike protein—and triggers the production of specific antibodies capable of binding to that protein. “An antibody and a protein work much like a key and a lock. If we identify the antibody capable of binding to the Spike protein, we can use it to detect the presence of the virus and thus establish an even more reliable and rapid diagnosis.”
Although it may seem simple at first glance, the task is nonetheless challenging because many “decorative” elements on the spike protein—such as sugars, for example—can influence how the antibody targets it, thereby requiring researchers to expand their characterization efforts. “Our molecular analysis must be extremely detailed and take into account the different environments of the spike protein in various samples collected from different types of patients—whether in intensive care or not, asymptomatic or not,” the researcher continues.
To collect these samples, the Clinical Proteomics Platform was able to rely on the collaboration of the university hospital’s biological resource center, which has been storing patient samples since the start of the epidemic, as well as on the virus bank atthe Pasteur Institute in Lille, a partner in the study. “We are expanding our sources and samples to obtain results that can be applied in practice; otherwise, we remain in the realm of basic science,” says Christophe Hirtz. “Our goal is truly to develop an optimized diagnostic test.”
Understanding the variety of symptoms
A diagnostic test—and perhaps even more than that—since analyzing the spike protein in different settings could also provide a better understanding of the diversity of symptoms associated with SARS-CoV-2. “We will compare samples from patients who reported an extremely severe form of COVID-19 with those from patients who developed a milder form, to see if there are any small differences in this Spike protein that might explain the diversity of cases we are observing.”
Scheduled to last 18 months, this project led by Sylvain Lehmann, head of the LBPC, is expected to yield initial results soon, after which researchers will be able to establish the profile of the antibody capable of targeting the spike protein. From there, two possibilities exist: “either the antibody already exists on the market—since there are a multitude of synthetic antibodies—and designing the test will be relatively straightforward to implement, or it does not exist and will need to be produced. ” For this final phase, researchers at the Clinical Proteomics Platform have secured the collaboration of the Montpellier-based company IdVet, another project partner, “but the cost and timeline will be different. It takes about six months to produce a purified antibody,” the researcher concludes.
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*LBPC (University of Montpellier, Inserm, Montpellier University Hospital)