These neutralizing effects were found to be comparable to or better than those seen with antibody candidates derived from patients who had recovered from COVID-19. The data were collected from studies conducted by Saint Louis University and independently verified by scientists at Colorado State University.
“These data are encouraging and provide powerful validation of our ability to generate well characterized and potent antibodies from our proprietary libraries. Importantly, the neutralizing effects seen in these in vitro studies suggest that infections in humans could be blocked,” said Emily M. Leproust, Ph.D., CEO and cofounder of Twist. “We are now evaluating the best path forward for these neutralizing antibodies to support the fight against COVID-19.”
The in vitro studies involved testing more than 200 well characterized monoclonal antibody and VHH nanobody candidates against live virus and pseudovirus cells. Each antibody was chosen for its high and unbiased binding affinity to either the receptor binding domain of the S1 protein of SARS-CoV-2 or the extracellular domain of ACE2 in human cells. The candidates were identified by Twist Biopharma, a division of Twist Bioscience, in just six weeks by screening its proprietary synthetic antibody discovery libraries each containing more than 10 billion antibody sequences, and within months produced robust neutralization data in live virus cells. The full data sets can be seen on the Twist website here and will be submitted to a peer-reviewed journal for publication.
“All antibodies moving through clinical development for the treatment of COVID-19 are full IgG antibodies and already show promise in early studies,” said James D. Brien, Ph.D., of Saint Louis University, School of Medicine. “The single domain (VHH) nanobodies included in these neutralization assays may represent a different therapeutic path to treat the disease. Given their very small size in comparison to IgG antibodies, they may be able to access epitopes on the virus that are unavailable to full IgGs.”
“Neutralizing antibodies have the potential to provide protective effects in treating patient with SARS-CoV-2 infection,” commented Richard Bowen, D.V.M., Ph.D., of Colorado State University. “The results from both the IgG and VHH antibodies generated by Twist Biopharma warrant advancement of several of these compounds into animal studies and potentially into human clinical trials.”
About 75 percent of the antibodies in the blood are IgGs. IgGs are made up of two heavy protein chains and two light protein chains that must pair together and cooperate to specifically recognize a target, in this case the Spike Protein on SARS-CoV-2. This specific targeting affords our immune systems “memory,” allowing it to selectively and precisely eliminate pathogenic threats.
Target recognition by VHH single domains, on the other hand, requires just a single domain found on heavy chain only antibody. With VHH-based antibodies able to exhibit pharmaceutically relevant properties comparable to IgGs, they are a promising therapeutic with several advantages over their bulkier, more complex, counterparts. The small size of VHH antibodies means they can squeeze into spaces and bind or block to parts of molecules that would otherwise be inaccessible to human IgG antibodies. They are also more thermally- and chemically-stable making VHH-based therapeutics good candidates to address respiratory infections, administered by inhaler directly to the respiratory tract where the infection is concentrated. In addition, the small size simplifies manufacturing of VHH antibodies.
In addition to SARS-CoV-2, Twist Biopharma discovers and develops IgG and VHH antibodies to numerous different targets for partners and internal development.
Source: Company Press Release