A deeper picture of vaccine effectiveness Researchers in the FuncMAB project are developing high-throughput methods to analyse the functionality induced by individual antibodies, helping to build a deeper and more resolved picture of protection on the single-antibody level, seeking answers to why people respond differently to vaccination, as Dr. Klaus Eyer explains. The method by which the effectiveness of vaccines is assessed has remained largely unchanged for over a century. Essentially, a blood sample is taken from an individual following vaccination, and the concentration of antibodies is measured. “We check whether an individual has antibodies or not on the cellular level,” explains Klaus Eyer, a Professor in the Department of Chemistry and Applied Biosciences at ETH Zurich. As the Principal Investigator of the EU-funded FuncMAB project, Professor Eyer is now looking at this from a different angle. “We know that these antibodies are produced by cells, and that a healthy human being has around 5,000 different antibodies against various pathogens in their bloodstream. We want to analyse every antibody, by itself, for its functionality, its capacity to protect,” he outlines. “It helps here that every cell basically produces – at a given time point – only one antibody. So if we analyse individual cells, we can analyse individual antibodies, and then try to reassemble our functional analysis into a global measurement of protection and its duration.” www.euresearcher.com
Vaccine protection and functional antibodies This enhanced resolution on the level of individual antibodies could lead to the identification of signatures that allow researchers to better determine who is protected by a vaccine , and to understand why certain individuals are not protected after vaccination. While a vaccine that stimulates the production of a large quantity of antibodies is often highly effective, this is not invariably the case. “We know some vaccines that have been shown to be effective don’t actually stimulate the production of a lot of antibodies. There are also examples of vaccinations that didn’t protect, despite leading to quite a high antibody response,” explains Professor Eyer. Within the project, Professor Eyer and his colleagues are working to build a deeper picture of the antibodies produced following vaccination and their effectiveness through research conducted largely on mice for the moment to develop suitable assays and understand the basic mechanisms of antibodies. “It’s not enough simply to have antibodies, they have to do something,” he stresses. “If you are infected by a virus, you need antibodies to neutralise it. For a bacterial infection, you need to eliminate
it by activating the innate immune system using antibodies that are able to do so.” The primary aim in the project is to develop high-throughput assays that allow researchers to measure the functionality of single antibodies in this respect. This project is not about developing a vaccine against a specific disease but rather building a deeper understanding of how the protection provided by vaccines against different diseases can be measured. “For example, for viruses, we can measure how many neutralising antibodies you generate, in relation to all the antibodies as a whole. In a further step, we can then work on increasing this proportion. For example, a simple but complicated question: How can you induce more neutralising antibodies for a longer time? It all starts being able to precisely measure the antibodies.” says Professor Eyer. “We’ve also worked on a bacterium that can infect the brain and cause an inflammatory reaction. We know that we need to have antibodies that activate the complement system against this bacteria. We can look to measure how many antibodies an individual has. Is there a way to increase the amount of antibodies to better protect individuals?”
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