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Researchers led by scientists from the National Institute of Allergy and Infectious Diseases (NIAID) have developed antibodies that can bind two different antigens at the same time, targeting multiple regions of the SARS-CoV-2 spike protein
.
These bispecific antibodies successfully neutralized the original virus as well as the Alpha, Beta, Gamma and Delta variants
The worryingly emerging SARS-CoV-2 variant threatens the effectiveness of existing vaccines
.
To neutralize the mutations that occur in infected patients and guide vaccine design, there is an urgent need for other effective antibody-based therapies targeting multiple sites in the spike protein
The author points out: “Faced with the rapidly emerging SARS-CoV-2 mutation, this poses a challenge to our efforts to end the pandemic.
Our findings support further exploration of bispecific antibodies that strategically combine antibody pairs.
As a new tool to treat COVID-19
.
"
These findings were published this week in the journal Science Translational Medicine
.
Currently, COVID-19 antibody therapy is injected with a cocktail of single monoclonal antibodies targeting specific areas of the virus
.
Most researchers who develop SARS-CoV-2 specific monoclonal antibodies use the antigen probe method to isolate memory B cells or a mixture of plasmablasts and memory B cells
The current research led by NIAID scientists Peter Crompton, MD and Joshua Tan, Ph.
D.
, shows that combining selected monoclonal antibodies into bispecific antibodies can produce antibodies that are stronger than monoclonal cocktails
.
A bispecific antibody made by the researchers is 100 times more potent in vitro than a cocktail of its monoclonal parents
In addition, the current research does not rely on cell sorting based on antigen probes, and a large number of monoclonal antibodies are produced from plasmablasts and memory B lymphocytes of patients recovered from COVID-19
.
Instead, they combined effective monoclonal antibodies with non-overlapping regions of viral spike proteins to generate bispecific antibodies
The research team showed their two bispecific antibodies, which neutralized the original virus as well as Alpha, Beta, Gamma and Delta variants
.
The three most effective bispecific antibodies they have made target different regions of the receptor binding region of the spike protein.
The most effective bispecific antibody (CV503) binds to the ridge of the SARS-CoV-2 receptor binding area and competes with the angiotensin converting enzyme 2 receptor, which is a host protein that binds to the viral spike protein
.
Through the analysis of the crystal structure, the authors found that CV503 has the least contact with key variant residues K417, E484 and N501
In order to prove the potential therapeutic applicability, the authors demonstrated that two bispecific antibodies protect hamsters from clinical diseases at a dose of 2.
5 mg/kg body weight
.
The authors show that a bispecific antibody neutralizes the Beta variant in vitro and protects hamsters from SARS-CoV-2 expressing the E484K mutation
.
The research team developed bispecific antibodies from 216 monoclonal antibodies against SARS-CoV-2
.
They collected these monoclonal antibodies from plasmablasts and memory B cells of recovering COVID-19 patients and screened their antiviral efficacy
.
They identified five bispecific antibodies that inhibit the virus at concentrations less than 1 ng/mL
.
Part of the reason why these bispecific antibodies are particularly effective against SARS-CoV-2 mutations is that they are designed to bind to the non-overlapping regions of the viral peak and will not infringe on the regions of the viral peak protein, which will be affected by new mutations.
And change
.
The author points out: "Bispecific antibodies represent a promising strategy for the next generation against SARS-CoV-2 mutations
.
"
Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern .
