Versatile coronavirus antibody may be starting point for broader-acting vaccines
A
special type of antibody is produced in patients who've had COVID-19 as well as
less-serious coronaviruses that cause colds
Scripps
Research Institute
That's because at least four coronaviruses in the same general family as SARS-CoV-2 cause the benign yet annoying illness known as the common cold.
In a new study that appears in Nature Communications, scientists from Scripps Research investigated how the immune system's previous exposure to cold-causing coronaviruses impact immune response to COVID-19.
In doing so, they discovered one cross-reactive
coronavirus antibody that's triggered during a COVID-19 infection.
The findings
will help in the pursuit of a vaccine or antibody treatment that works against
most or all coronaviruses, says senior author Raiees Andrabi, PhD, an
investigator in the Department of Immunology and Microbiology.
"By
examining blood samples collected before the pandemic and comparing those with
samples from people who had been sick with COVID-19, we were able to pinpoint
antibody types that cross reacted with benign coronaviruses as well as
SARS-CoV-2," says Andrabi, who works closely with the laboratory of
professor Dennis Burton, PhD.
In later tests,
the antibody also neutralized SARS-CoV-1, the coronavirus that causes SARS, or
severe acute respiratory syndrome.
"We were able to determine that this type of cross-reactive antibody is likely produced by a memory B cell that's initially exposed to a coronavirus that causes the common cold, and is then recalled during a COVID-19 infection," Andrabi says.
Memory B cells
are an essential part of the immune system. They "remember" initial
disease threats and can circulate in the bloodstream for decades, ready to be
called back into action if the threat emerges again. These cells are
responsible for producing targeted antibodies.
The discovery
may be an important step in the eventual development of a pan-coronavirus
vaccine, which would be able to protect against potential coronaviruses that
emerge in the future, says Burton, the James and Jessie Minor Chair in
Immunology in the Department of Immunology & Microbiology at Scripps Research.
"Another
deadly coronavirus will likely emerge again in the future -- and when it does,
we want to be better prepared," Burton says. "Our identification of a
cross-reactive antibody against SARS-CoV-2 and the more common coronaviruses is
a promising development on the way to a broad-acting vaccine or therapy."
Burton's lab is
also investigating broadly neutralizing antibodies that can be harnessed to
protect against many forms of influenza, which is another virus likely to cause
a pandemic in the future.
In the new
study, the team used electron microscopy to understand how the cross-reactive
antibody is able to neutralize a range of coronaviruses. They saw that it
mostly binds to the base of the virus's spike protein, an area that doesn't
change much from strain to strain, says first author Ge "Sophie"
Song, a graduate student in the Burton laboratory.
"The study
highlights how important it is to fully understand the nature of preexisting
immunity, especially in regard to coronaviruses," Song says. "Earlier
exposure to a coronavirus, even a benign virus that causes colds, impacts the
nature and level of antibodies produced when more serious coronavirus threats
emerge."
The study,
"Cross-reactive serum and memory B-cell responses to spike protein in
SARS-CoV-2 and endemic coronavirus infection," is authored by Ge Song,
Wan-ting He, Sean Callaghan, Fabio Anzanello, Deli Huang, James Ricketts,
Jonathan Torres, Nathan Beutler, Linghang Peng, Sirena Vargas, Jon Cassell,
Mara Parren, Linlin Yang, Caroline Ignacio, Davey Smith, James Voss, David
Nemazee, Andrew Ward, Thomas Rogers, Dennis Burton and Raiees Andrabi.
Funding for this
research was provided by NIH CHAVD and R01 awards, the IAVI Neutralizing
Antibody Center, the Bill & Melinda Gates Foundation, the John and Mary Tu
Foundation and the James B. Pendleton Charitable Trust.