Tackling COVID-19 with Human Neutralizing Antibodies

With Davide Corti, SVP, Antibody Research at Humabs BioMed SA Summary by Candace Kastanis

Tackling COVID-19 with Human Neutralizing Antibodies

Candace Kastanis reviews a popular talk presented by Davide Corti, SVP, Antibody Research at Humabs BioMed SA.

Corti opened with some factual elements pertaining to antibody research.He noted that up until now there have been 13 approved mAbs. They were approved for emergency use and modality.The platform and basis for the above research is the isolating the antibodies that have increased efficiency in fighting infectious disease – in this case, COVID-19.He outlined the process for isolating effective antibodies for preclinical drug development which included:

Identifying survivors with best possible antibodies.

Screening 100s of millions of B cells from those survivors for rare human antibodies with desired characteristics

Engineering Fab and FC regions of those rare antibodies to enhance efficacy

Transferring protective immunity to at-risk individuals

Understanding the Seven Coronaviruses Infecting HumansThis was an important part of the summary because it notated the closely tied proximity of variations between 2003 to 2019 in which the three distinct types emerged into the population.Corti expressed high interest in helping us understand the 2012 emergence of the Mers-Cov type and the 2019 type SARS-cov-2.The major takeaway is that understanding this evolution will help to find an antibody capable of handling the diversity of the coronavirus subtypes.

About S309

S309 was isolated from memory B cells of a SARS-Cov2 survivor infected in 2003. S309 shows potent in vitro neutralization of SARS-CoV2 Virus and diverse COV pseudoviruses.

Specific S309 Characteristics:

Binds to both upward and downward facing SARS-CoV2 receptor binding domains
Recognizes a highly conserved glycan containing epitope on the RBD
Is highly conserved between SARS-CoV and SARS- CoV2
Does not overlap to the ACE2 receptor and does not interfere with block ACE2 binding.
S309 blocks S fusogenic activity
S309 blocks lectins enhanced SARS-CoV2 viral entry
It was noted that ACE2 over-expressing cells inadequately measure the neutralizing activity of non-RBM antibodies
Cells that overexpress the ACE2 effectively measure the neutralizing activity of the RBM antibodies.
Was shown to protect hamsters against SARS-CoV2
Effectively triggers effector functions potential relevant for controlling respiratory virus infection

S309 Activity in Animal Models – Fc ReceptorsFc receptors engagement are needed for protection in animal models.In Humabs’ study, they also found no correlation between in vitro neutralization and in vivo potency.Additionally, they found that Fc receptor- dependent effector functions contribute actively towards in-vivo protection.Emergence of COVID –19 MutationsCorti paved a picture for why modifications are necessary in tackling known variants and future ones. The most influential variant at this time has been noted to evolve from the UK.An evolution tree was used as a schematic to illustrate where the origin of the variants is and their impact on various parts of the world.The schematic also pointed out similarities within the variants. This is important to realize the characteristics that COVID-19 share with the other mutations.Interspecies Transmission Mutations seems to be an area of concern as the virus has shown the ability to affect other animals. It may show the basis for the evolution of the virus into individuals.It was suggested that there may be evidence of ping-pong affect regarding virus transmission.Antigenic Drift in Influenza – Will SARS-COV2 do the same?Influenza virus forced a shift in vaccines because the evolution of the H1N1 virus from 1999 adapted into another mutation of H1N1 in 2006.This provided a clue of the possibility SARS-COV2 could do the same and, as a result, require a modified vaccine to act towards transmission protection.A study compared points of intersection between both viruses pointed out the antigenic drift is imminent.Testing VIR 7831 (Sotrovimab) for Clinical EfficacyVIR 7831 was engineered to have high potent and long-lasting effects from SARS-COV2 and other COVs. Potential treatment applications include:

Improved lung bioavailability

Blocks viral entry

Extended half life

Low dosage requirements

High barrier to resistance

The Mechanism of Action (MOA) of VIR 7831 works by clearing infected cells by recruiting the immune system.The benefits of using VIR 7831 for treatment was shown in clinical studies to affect patient outcomes by a 85% reduction in hospital or death in adult at risk outpatients, and also a 70% reduction in persistent high viral load.As a result of the positive study data, the use of VIR 7831 is being filed for emergency use in the USA for the treatment of SARS-COV2 patients.In conclusion, the scope of prophylactic + therapeutic approaches to COVID-19 using results from other studies featuring antibodies. Corti provided evidence that complimentary or adjunctive vaccines feature high efficacy in affected individuals.The need for more studies was also a key factor in the conclusion through the characteristics found in mRNA-based research modalities.He pointed out that reprogramming effector functions and half-life can enhance the mAb therapeutic potential.Lastly, the prospect of accelerated manufacturing, higher yields, and lower costs to help to meet the needs of more affected individuals of infectious disease was discussed.