Boston: Scientists have identified a human antibody that they say may potentially prevent or limit SARS-CoV-2 infection. It is due to the SARS-CoV-2 infection the COVID-19 disease happens.
The researchers are from the University of Massachusetts Medical School (UMMS) in the United States (US). They have discovered and characterised a cross-reactive human monoclonal antibody (MAB) to SARS-CoV-2 spike proteins which blocks ACE2 receptor binding on the mucosal tissue of the respiratory tract.
The origins of this rapid and important discovery go back 16 years, when the researchers at UMMS developed an IgG monoclonal antibody that was effective against a similar virus, SARS, according to the study published in the journal ‘Nature Communications’.
When SARS-CoV-2 was recognised and began to spread, the researchers realised that the first MAB might help with this new infection. They launched the process of resurrecting the old SARS programme, retrieving frozen cells that had been developed 16 years earlier, thawing them and determining if what worked for one novel coronavirus would work for another.
Although there was 90 per cent similarity between the two coronaviruses, the monoclonal antibody exhibited no binding to the current coronavirus, the researchers said.
The team drew its experience with a separate research programme to develop ‘secretory IgAs (sIgA)’, antibodies that play a crucial role in immunity on mucosal surfaces. The approach worked, producing an antibody with binding affinity and neutralisation activity. This antibody was designated MAb362.
“We were excited to learn that antibodies to SARS-CoV-2 are more effective in binding to and neutralising the virus when they are in the sIgA isotype of antibody, compared to the usual circulating IgG antibodies,” said Mark Klempner, a professor of medicine at UMMS.
“In nature, sIgA antibodies coat mucosal surfaces like the respiratory, gastrointestinal infections (GI) and GU tracts, where they are stabilized by the mucous layer on these surfaces. There, they perform the important function of preventing binding of a pathogen to host cells, thus preventing infection,” Klempner informed.
Based on these results, the team worked with Celia Schiffer, a professor of biochemistry and her then-graduate student Shurong Hou, to see if they could understand the nature of the effect of the IgA antibody.
They found MAb362 shared a highly similar framework with MAb 80R, another SARS antibody with a crystal structure in complex with SARS-CoV.
A molecular model revealed a highly conserved protective epitope within the receptor-binding domain of the S protein. MAb362 neutralises authentic SARS-CoV-2 virus by directly out-competing the S protein’s binding to hACE2 receptors, the researchers found.
“So our search -which started during a coffee break conversation, has resulted in a unique IgA antibody that could potentially be applied through mucosal administration, in combination with other systemically administrated therapeutics for direct mucosal protection,” said Klempner.
