Researchers Identify COVID Specific IgA Monoclonal Antibodies that Provide Immunity Against Novel Coronavirus

A new study suggests that COVID specific IgA monoclonal antibodies could provide effective immunity in the respiratory system against the novel coronavirus, a potentially critical feature of an effective vaccine.

In their study published in Nature Communications, researchers at MassBiologics of the University of Massachusetts Medical School (Worcester, MA, USA) have described the discovery and characterization of a cross-reactive human monoclonal antibody (MAB) to SARS-CoV-2 spike proteins that blocks ACE2 receptor binding on the mucosal tissue of the respiratory tract, thus potentially preventing or limiting SARS-CoV-2 infection causing COVID-19 disease.

The origins of the discovery of this novel approach to prevent and treat SARS-CoV-2 infection go back 16 years, when MassBiologics had developed an IgG monoclonal antibody that was effective against SARS-CoV, the first severe acute respiratory syndrome caused by a novel coronavirus. When SARS-CoV-2 was recognized and began to spread, the researchers realized that that first MAB might help with this new infection. They launched the process of resurrecting the old SARS program, retrieving frozen hybridoma 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% similarity between the two coronaviruses, the monoclonal antibody exhibited no binding to the current coronavirus. The researchers then evaluated another MAB from that earlier work, which was also only weakly effective.

The researchers went on to draw from their experience with a separate research program to develop “secretory IgAs (sIgA),” antibodies that play a crucial role in immunity on mucosal surfaces. MassBiologics has been investigating sIgA in the GI tract as a possible therapeutic to prevent gastrointestinal infections. The researchers suspected that similar anti-SARS-CoV-2 sIgA produced passive mucosal immunity in the respiratory tract, where COVID-19 disease is incredibly damaging. Their approach worked, producing an antibody with binding affinity and neutralization activity that was designated MAb362. During their efforts to understand the nature of the effect of the IgA antibody, the researchers found that MAb362 shared a highly similar framework with MAb 80R, another SARS-CoV 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.

“We were excited to learn that antibodies to SARS-CoV-2 are more effective in binding to and neutralizing the virus when they are in the sIgA isotype of antibody, compared to the usual circulating IgG antibodies,” said Mark Klempner, MD, executive vice chancellor for MassBiologics and professor of medicine. “In nature, sIgA antibodies coat mucosal surfaces like the respiratory, 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.” MAb362 neutralizes authentic SARS-CoV-2 virus by directly out-competing the S protein’s binding to hACE2 receptors.

“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,” added Klempner.

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University of Massachusetts Medical School