COVID-19 Antibodies: University Of Massachusetts Medical School Discover Antibodies That Finally Show Proof Of Possible Protection Against COVID-19
: Researchers from University of Massachusetts Medical School have discovered COVID specific IgA monoclonal antibodies that may provide effective immunity in the respiratory system against the SARS-CoV-2 coronavirus, a potentially much needed critical feature of an effective vaccine.
The research findings were published in the journal: Nature Communications. https://www.nature.com/articles/s41467-020-18058-8
Dr Yang Wang, MD, Ph.D., deputy director for product discovery at MassBiologics and Associate Professor of medicine, and colleagues describe the discovery and characterization of 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-potentially preventing or limiting SARS-CoV-2 infection causing COVID-19 disease.
The history of the origins of this rapid and important discovery go back 16 years, when MassBiologics, the research arm of University of Massachusetts Medical School developed an IgG monoclonal antibody that was effective against a similar virus, SARS (that was SARS-CoV, the first severe acute respiratory syndrome caused by a novel coronavirus). That first SARS virus caused alarming illness, but then disappeared; MassBiologics, which was ready at the time to initiate a clinical trial, saved the research materials associated with that work.
When news of SARS-CoV-2 broke out, MassBiologics researchers realized that that first monoclonal antibodies (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.
Though there was 90 percent similarity between the two coronaviruses, the monoclonal antibody exhibited no binding to the current coronavirus.
The study team then evaluated another MAB from that earlier work, which was also only weakly effective.
Being undeterred, the study team thought about their experience with a separate research program to develop "secretory IgAs (sIgA)," antibodies that play a crucial role in immunity on mucosal surfaces.
The researchers at MassBiologics have been investigating sIgA in the GI tract as a possible therapeutic to prevent gastrointestinal infections. Would similar anti-SARS-CoV-2 sIgA produce passive mucosal immunity in the respiratory tract, where COVID-19 disease is incredibly damaging? The approach worked, producing an antibody with binding affinity and neutralization activity. This antibody was designated MAb362.
Dr Mark Klempner, MD, executive vice chancellor for MassBiologics and Professor of medicine said, “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.”
He further added, "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."
Armed with these results, MassBiologics worked with Dr Celia Schiffer, Ph.D., the Gladys Smith Martin Chair in Oncology, Professor of Biochemistry & molecular pharmacology, and director of the Institute for Drug Resistance, and her then-graduate student, Dr Shurong Hou, who has since completed her studies and earned her Ph.D., to see if they could understand the nature of the effect of the IgA antibody.
Professor Schiffer and Dr Hou found 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. MAb362 neutralizes authentic SARS-CoV-2 virus by directly out-competing the S protein's binding to hACE2 receptors.
Dr Kempler added, "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."
As vivo studies in animal models have already demonstrated its neutralizing efficacy, the team is also planning human trials shortly.
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