Spike, the spy in the service of screening

What if the solution to the ever-growing queues at screening centers could be summed up in one word: SPIKE? Five letters that sound like a code name for a virus-specific protein that could form the basis of a new, faster and more effective test for Sars-Cov-2. and more effective.

PCR or serological test? Nasopharyngeal, blood or saliva sampling? Since the start of the epidemic, screening has become part of our lives, and with it comes its own set of questions: waiting times, reliability, discomfort... " The tests used today are not optimal. The tests used today are not optimal, and we're working on new solutions that will not only increase testing capacity, but also improve their sensitivity and specificity", explains Christophe Hirtz, researcher at the Biochemistry and Clinical Proteomics Laboratory*.

Spike, a specific protein

Unlike PCR (Polymerase Chain Reaction) tests, which seek to detect the presence of the virus genome, Elisa blood or saliva tests detect specific proteins found in large quantities on the virus envelope. "One of these proteins, which we call the Spike protein, is of particular interest to us because it has a sequence specific to the virus and is decisive for its entry into the cell. If we find this sequence, we're dealing with Sars-Cov-2. You can't go wrong", continues the researcher.

To detect this Spike protein, Christophe Hirtz and his team use mass spectrometry. Mass spectrometry is an analytical tool used to locate and identify molecules by their mass, and to characterize their chemical structure. "Mass spectrometry will enable us not only to characterize the protein, but also to understand the antigenicity of the virus - in other words, how our immune system will recognize the virus and trigger the right antibodies."

Identifying Spike with antibodies

In fact, when a virus enters our body, our immune system identifies a characteristic protein - in this case Spike - and triggers the production of specific antibodies, capable of capturing this protein. "An antibody and a protein work a bit like a key and a lock. If we can identify the antibody capable of capturing the Spike protein, we'll be able to use it to detect the presence of the virus and thus establish an even more reliable and rapid diagnosis."

Simple in appearance, the task is no less arduous, since many of the "decorative" elements present on the Spike protein, such as sugars for example, can play a part in the way the antibody will target it, forcing the researchers to extend their characterization work. " Our molecular analysis has to be extremely fine-tuned, taking into account the different environments of the Spike protein, in different samples taken from different types of patient, in intensive care or not, asymptomatic or not", continues the researcher.

To collect these samples, the Clinical Proteomics Platform was able to count on the collaboration of the CHU's biological resources center, which has been storing patient samples since the start of the epidemic, as well as on the virothèque of theInstitut Pasteur de Lille, a partner in the study. We're multiplying sources and samples in order to obtain applicable results, otherwise we'll remain in the realm of fundamental science," says Christophe Hirtz. Our aim is to come up with an optimized diagnostic test.

Understanding the diversity of symptoms

A diagnostic test and perhaps even more, as analysis of the Spike protein in different environments could also provide a better understanding of the diversity of symptoms associated with Sars-Cov-2. "We're going to compare samples from patients who have reported an extremely virulent form of Covid-19 with others who have developed a milder form, and see if there are any small differences in this Spike protein that would explain the diversity of cases we're seeing."

Scheduled to run for 18 months, this project, led by Sylvain Lehmann, head of the LBPC, should rapidly produce initial results, enabling researchers to establish the profile of an antibody capable of targeting the Spike protein. From there, there are two possibilities: "either the antibody already exists on the market, as there are a multitude of synthetic antibodies, and the design of the test will be relatively simple to set up, or it doesn't exist and will have to be produced". For this final phase, the researchers at the Clinical Proteomics Platform have enlisted the help of IdVet, another project partner from Montpellier, "but it won't be the same price, nor the same time. It takes about six months to manufacture a purified antibody", concludes the researcher.

*LBPC (UM, Inserm, CHU de Montpellier)