BREAKING! COVID-19 Research: Mutated SARS-Cov-2 Spike Protein Variants Evade Neutralizing Antibodies. Warning Of Emergence Of Antibody-Resistant Variants
: Scientists from the Rockefeller University-New York, New York Blood Center, Università della Svizzera italiana,-Switzerland and Howard Hughes Medical Institute have discovered in a new study that mutated SARS-Cov-2 spike protein variants can evade neutralizing antibodies .
Furthermore the researchers warn that the emergence of antibody-resistant SARS-CoV-2 variants might limit the therapeutic usefulness of monoclonal antibodies.
Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations.
The study findings were published on a preprint server and are currently being peer-reviewed. https://www.biorxiv.org/content/10.1101/2020.07.21.214759v1.full.pdf
Neutralizing antibodies are a key component of adaptive immunity against many viruses that can be elicited by natural infection or vaccination. Antibodies can also be administered as recombinantly produced proteins or as convalescent plasma to confer a state of passive immunity in prophylactic or therapeutic settings.
Studies have shown that related, potently neutralizing monoclonal antibodies that recognize the SARS-CoV-2 receptor binding domain (RBD) are often elicited in SARS-CoV-2 infection. These antibodies have great potential to be clinically impactful in the treatment and prevention of SARS-CoV-2 infection.
However, a significant fraction of COVID19 convalescents, including some from whom potent neutralizing antibodies have been cloned, exhibit low levels of plasma neutralizing activity. Together, these findings suggest that natural SARSCoV-2 infection may often fail to induce sufficient B-cell expansion and maturation to generate high titer neutralizing antibodies.
The degree to, and pace at which SARS-CoV-2 might evolve to escape neutralizing antibodies is unclear. The aforementioned considerations raise the possibility that SARS-CoV-2 evolution might be influenced by frequent encounters with sub-optimal concentrations of potently neutralizing antibodies during natural infection. Moreover, the widespread use of convalescent plasma containing unknown, and often suboptimal, levels of neutralizing antibodies might also increase the acquisition of neutralizing antibody resistance by circulating SARS-CoV-2 populations
. Reinfection of previously infected individuals who have incomplete or waning serological immunity might similarly drive emergence of antibody escape variants.
The researchers used a recombinant chimeric virus approach that can rapidly generate and evaluate SARS-CoV-2 S mutants that escape antibody neutralization.
They showed that mutations conferring resistance to convalescent plasma or RBD-specific monoclonal antibodies can be readily generated in vitro. Notably, these antibody resistance mutations are present at low frequency in natural populations.
These SARS-CoV-2 S protein variants typically have mutations in the receptor binding domain (RBD) and N-terminal domain.
The mutations observed using various cell cultures and antibodies were E484K and Q493K/
R within the RBD and these were present at high frequencies, R346K/S/L and N440K mutations within RBD encoding sequence, K444R/N/Q and V445E that were also abundant ,mutations outside the RBD, specifically at N148S, K150R/E/T/Q and S151P in the N-terminal domain (NTD) were also abundant.
This revelation could have impacts on current antibody and vaccine developments and researchers are urged to pay more detailed attention to these emerging antibody resistant variants.
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