Neutralizing Antibody Development for SARS-CoV-2

Emerging pathogens and epidemic diseases are global challenges for public health. In December 2019, the pneumonia outbreak in the city of Wuhan, China is induced by a newly identified coronavirus (SARS-CoV-2). Coronavirus is a type of enveloped RNA virus that is widely distributed among humans and other species and that causes respiratory, enteric, and neurologic disorders.

As a top-class partner in the biotechnological area, Creative Biolabs is constantly looking over this novel coronavirus for precious diagnosis and effective treatment. It is known that neutralizing antibodies (nAbs) are major contributors to protect responses against most viral invaders. Enabled by proprietary technology platforms, we have organized a team with the superior expertise for the research of ongoing SARS-CoV-2 infection and to develop multiple neutralizing antibodies.

Fig.1 Analysis of the functional domains in 2019-nCoV spike protein and its gene. (Jiang, 2020)

Same as all other coronaviruses, the genome of SARS-CoV-2 encodes the spike protein, the nucleocapsid protein, the envelope protein, and the membrane protein. The spike protein (S-protein) contains two subunits, S1 and S2, and is responsible for receptor binding and membrane fusion. This region is the common target for neutralizing antibodies and clinical vaccines. The nucleocapsid protein (N-protein) is the most abundant domain in coronavirus. It is a greatly immunogenic phosphoprotein with high conservation and often works as a biomarker in diagnostic assays.

Fig.2 Determinants of broadly neutralizing antibodies (bnAbs) induction suggested by studies. (Abela, 2019)

Neutralizing Antibody Development for SARS-CoV-2 at Creative Biolabs

Neutralizing antibodies are a critical specific defense against viral infections. They not only bind to a virus but bind in a manner that blocks invaders. A neutralizing antibody targeting the S-protein on the surface of SARS-CoV-2 is likely to be the first therapy considered in academia, offering passive immunity to diseases.

The currently published genome sequence of SARS-CoV-2 allows us to accomplish gene synthesis and protein expression as an immunogen in the lab. Developing neutralizing antibodies through polyclonal antibody technology would be to immunize animals (e.g. sheep, goat, and cow) with SARS-CoV-2 S-protein, and subsequently purifying polyclonal antibodies from these hosts. This way might serve as an expedited service in the context of an outbreak and bring many advantages, including simplified production and manufacturing. Other traditional approaches (such as hybridoma technique) for neutralizing antibodies discovery also can be performed. Notably, there are several faster approaches such as using yeast or phage display libraries to identify specific peptide or antibody fragments, which can be drug candidates against SARS-CoV-2. In the field of applying phage display technology, Creative Biolabs has extensive expertise, which has been accumulated through our over decade experience. Integrated with our various types of in-house phage display libraries and different screening strategies, we are pleased to offer the most comprehensive services based on phage display platform.

With extensive antibody development and manufacturing experience in the fields of infections, our team is committed to the development of neutralizing antibodies through the following subjects and accelerating therapeutic strategies against SARS-CoV-2 infections.

• CR3022 as a Target for SARS-CoV-2 Antibody Development
• CD4 as a Target for SARS-CoV-2 Antibody Development
• Glycoprotein as a Target for SARS-CoV-2 Antibody Development

Therapeutic Human Monoclonal Antibodies from COVID-19 Recovered Patient Sera

Neutralizing antibodies from recovered patient sera can be used to prevent infections in contacts, and can also be used to treat sick people, which is called "passive antibody therapy". The results demonstrated that the plasma in the recovery phase has the potential to improve the clinical outcome of severe COVID-19 patients by neutralizing viremia. Creative Biolabs now provides therapeutic human monoclonal antibody screening services from COVID-19 recovered patient sera via its advantage in antibody discovery.

Therapeutic Human Monoclonal Antibodies from SARS-CoV-2 Surface Protein Immunized Humanized Antibody Mice

Creative Biolabs can provide the service of immunizing humanized antibody mice with SARS-CoV-2 surface protein to screen for therapeutic human monoclonal antibodies. We have self-cultivated humanized antibody mice, through the immunization of the S-RBD protein antigen and use the hybridoma fusion protocol to conduct the discovery study of human monoclonal antibodies for COVID-19 treatment. Through hybridoma fusion combined with semi-solid screening, we have screened a certain number of hybridoma cell lines that can efficiently bind S-RBD. Through the blocking experiment of RBD protein binding to ACE2, we further selected hybridoma clones with high blocking effect and high affinity for live virus neutralization experiments, and obtained hybridomas with live virus neutralization effect. The recombinantly expressed neutralizing antibody has better affinity and neutralizing activity than other neutralizing antibodies.

Confronted by this severe epidemic situation, Creative Biolabs has taken immediate actions to facilitate the research and development of broadly neutralizing antibodies for SARS-CoV-2. We’d like to actively work together with global hospitals, medical institutions, biological companies, and also provide CRO services for effective antibodies to win this battle. For more information, please directly contact us or consult our technical supports online.

References

1. Jiang, S.; et al. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies. Emerging Microbes & Infections. 2020, 9(1): 275-277.
2. Abela, I.A.; et al. Correlates of broadly neutralizing antibody development. Wolters Kluwer Health. 2019, 14(4): 280-285.

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