Scientists at the InfectoGnostics Research Campus Jena have developed a new microarray that can detect antibodies against a wide range of infectious agents. With a single drop of the patient’s blood, it is thus possible to test whether the immune system has responded to a vaccination or if there is antibody-mediated immunity after infection. The campus partners Leibniz Institute of Photonic Technologies (Leibniz IPHT), fzmb GmbH, Virion\Serion GmbH and the Jena University Hospital cooperated to develop and validate the test.

To defend itself against infectious diseases and foreign substances, the human immune system produces special proteins against the pathogen – so-called antibodies. However, these antibodies are not directed against the entire pathogen, instead they always bind to very specific molecular structures of the intruder via a lock-and-key principle. These structures are also known as „antigens“. InfectoGnostics scientists have now developed a test platform in the RESISTOVAC project, on which dozens of such antigens can be applied. A single drop of the patient’s blood can thus be used to test in parallel for several antibodies against common and new infectious diseases.

The central focus of the development was initially a more precise screening of the immune reaction to the coronavirus. A so-called protein microarray was used for this: This is a chip a few millimetres in size on which various antigens are applied as capture molecules. If antibodies from the patient’s blood are brought together with the matching antigens on the chip, a specially developed method leads to a staining of corresponding spots on the microarray – a targeted antibody must therefore have been present in the blood.

In order to validate the reliability of this detection, the InfectoGnostics researchers applied different SARS-CoV-2 antigens to the microarray and tested them against real samples from Covid-19 patients from Thuringia: „We wanted to detect the relatively late-formed IgG antibodies – a kind of long-term memory of the immune system against components of a pathogen. To detect them, we applied 18 antigen combinations for the coronavirus as capture molecules,“ explains Sindy Burgold-Voigt, first author of the study and doctoral student at Leibniz IPHT.

Cooperation of several partners from the InfectoGnostics research campus

The microarray was designed by Leibniz IPHT scientists from the Optical-Molecular Diagnostics and Systems Technology Department headed by Prof. Ralf Ehricht, together with developers from fzmb GmbH in Bad Langensalza. The microarray was finally manufactured on the basis of the „Inter-Array“ system from the fzmb GmbH. Another company partner of InfectoGnostics, Virion\Serion GmbH, also provided antigens for Corona and other pathogens.

For antigen referencing and validation of the test, the Jena University Hospital contributed biobank samples and data from their 2020 Corona study „CoNAN“ in Neustadt am Rennsteig. The village in northern Thuringia was completely quarantined at the beginning of the pandemic and systematically recorded by Jena University Hospital researchers in an epidemiological study.

Immune systems react extremely individually to coronaviruses

In their evaluation, the scientists found that the immune response varies greatly from individual to individual: for example, some patients had only developed antibodies against a protein that envelops the genetic material of the virus – the nucleocapsid. Other patients, however, had antibodies against the so-called spike protein – the pointed structures with which the virus attaches itself to human cells. Still others had matching antibodies against both corona antigens.

The clever combination of different antigens on a single test can thus be of great importance for the understanding of antibody immune defence and the work on new vaccines, explains Sindy Burgold-Voigt: „For the further development and efficiency analyses of vaccinations, it is extremely important that research has a diagnostic tool with which one can get a quick overview of the immune response.“

Microarray for all STIKO vaccinations could provide clues to vaccination gaps

In addition to various surface structures of the coronavirus, three antigens from the pathogens for diphtheria, measles and tetanus, to which vaccinated individuals typically react, were also put on the test. Here, a corresponding antibody response was successfully detected in vaccinated individuals. „We were thus able to show that we can flexibly extend the test and detect different antibodies during a single test in the patient’s blood. In the future, we could therefore compile a microarray for all vaccinations recommended by the STIKO, with which we could screen for possible vaccination gaps quickly and cheaply,“ explains Sindy Burgold-Voigt.

The test development was supported by the Federal Ministry of Education and Research as part of the InfectoGnostics lead project RESISTOVAC, which aims to develop POC tests to determine immune status and bacterial resistance factors. In addition, the study was funded by the state of Thuringia and co-financed by European Union funds under the European Social Fund (ESF).



The results were published in the scientific journal Scientific Reports.

About the InfectoGnostics Research Campus Jena

The InfectoGnostics Research Campus Jena is a public-private partnership breaking new ground in the diagnostics of infections and pathogens, such as viruses, bacteria and fungi. InfectoGnostics is funded by the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) under the funding initiative „Research Campus – Public-Private Partnership for Innovation“ with additional support from the state of Thuringia. About half of the required budget is financed by the participating partners. www.infectognostics.de

 

In the picture:
Using a microarray (left), InfectoGnostics researchers can simultaneously detect antibodies against SARS-CoV-2 (right) and against other infectious agents
, ©InfectoGnostics/BioRender.com