A Danish research team has developed a new and more rapid test method that determines whether a person’s antibodies continue to protect them – also against new variants.
The test shows that the antibodies formed against a specific part of the virus are far more protective than others. The new test could be an important tool in predicting when vaccination should be boosted, the researchers state.
“The test can therefore also determine which types of antibodies are most important in combating the virus and which parts of the virus they counteract.”
“We have developed a new test method that can determine very accurately and much more rapidly than existing tests how well our antibodies can neutralize variants of the virus. The test can therefore also determine which types of antibodies are most important in combating the virus and which parts of the virus they counteract. Tests like these can prove to be extremely important both in developing future vaccines, for antibody therapy and especially for monitoring when herd immunity decreases,” says Peter Garred, consultant at the Department of Clinical Immunology, Rigshospitalet and clinical professor, University of Copenhagen.
Based on a recombinant technique
Existing virus neutralization tests, including the plaque reduction neutralisation test, are accurate and good, but they are far too time consuming to use on a large scale. “We have therefore strived to develop an equally accurate but less elaborate test,” explains Garred.
The plaque reduction neutralisation test (PRNT) requires waiting to determine whether live SARS-COV-2 form visible plaques in cells or not, whereas the new assay is based on a recombinant technique producing the virus spike protein and the human angiotensin-converting enzyme-2 (ACE-2) receptor. Using these reagents, the researchers have shown that they can mimic whether antibodies in the blood can prevent the virus from infecting our cells.
This is measured using an enzyme-linked immunosorbent assay (ELISA), which is based on a colour change when the spike protein binds to ACE-2. The new antibody neutralisation test correlates very well with the PRNT assay.
Important for future vaccines and therapies
When SARS-CoV-2 infects human cells, the spike protein attaches itself to the surface of the cells and then penetrates it. SARS-CoV-2 needs the spike protein and specifically the fragment of protein that binds to the ACE-2 receptor to penetrate the cells. The fact that antibodies that bind to only this fragment of viral protein are the most effective is therefore not surprising.
“As the virus mutates, we must expect vaccines and artificial antibodies to adjust, and our experiments indicate which molecular structures in the spike protein developers of both vaccines and antibody-based therapy should focus on in the future.”
“However, we were somewhat surprised that the antibodies that linked specifically to the receptor-binding domain were far more effective. This is very important information both for future vaccines but also in developing more antibody-based therapy,” explains Garred. “Our experiments show that current antibody-based therapy and vaccination are extremely effective against SARS-CoV-2 in its current form. As the virus mutates, we must expect vaccines and artificial antibodies to adjust, and our experiments indicate which molecular structures in the spike protein developers of both vaccines and antibody-based therapy should focus on in the future.”