Antibodies that may protect against COVID-19

Date:
August 24, 2020
Source:
University of Massachusetts Medical School
Summary:
A new study suggests that COVID-19 specific IgA monoclonal
antibodies may provide effective immunity in the respiratory system
against the novel coronavirus -- a potentially critical feature
of an effective vaccine.



FULL STORY ==========================================================================
A new study by researchers at MassBiologics of UMass Medical School
published in Nature Communications suggests that COVID specific IgA
monoclonal antibodies may provide effective immunity in the respiratory
system against the novel coronavirus -- a potentially critical feature
of an effective vaccine.


==========================================================================
Yang Wang, MD, PhD, 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.

Like scientists around the world, the research leadership at
MassBiologics started talking about what became known as SARS-CoV-2
within days of the first cases of when the novel coronavirus were first reported. MassBiologics was in a unique position to respond, and those
early discussions have resulted in the discovery of a novel approach to
prevent and treat SARS-CoV-2 infection.

The origins of this rapid and important discovery go back 16 years, when MassBiologics 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 SARS-CoV-2 was recognized and began to spread, MassBiologics
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 percent similarity between the two coronaviruses, the monoclonal
antibody exhibited no binding to the current coronavirus. MassBiologics
then evaluated another MAB from that earlier work, which was also only
weakly effective.

Undeterred, Wang and colleagues 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. MassBiologics
has 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.

"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." Based on these results, MassBiologics worked with Celia
Schiffer, PhD, 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, Shurong Hou, who
has since completed her studies and earned her PhD, to see if they could understand the nature of the effect of the IgA antibody. Drs. Schiffer
and 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.

"So our search -which started during a coffee break conversation," said Klempner, "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."

========================================================================== Story Source: Materials provided by
University_of_Massachusetts_Medical_School. Original written by Mark
Shelton. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Monir Ejemel, Qi Li, Shurong Hou, Zachary A. Schiller, Julia
A. Tree,
Aaron Wallace, Alla Amcheslavsky, Nese Kurt Yilmaz, Karen
R. Buttigieg, Michael J. Elmore, Kerry Godwin, Naomi Coombes,
Jacqueline R. Toomey, Ryan Schneider, Anudeep S. Ramchetty,
Brianna J. Close, Da-Yuan Chen, Hasahn L. Conway, Mohsan Saeed,
Chandrashekar Ganesa, Miles W. Carroll, Lisa A. Cavacini, Mark
S. Klempner, Celia A. Schiffer, Yang Wang. A cross-reactive
human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2
interaction. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020- 18058-8 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200824110122.htm

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