Bovine-derived antibodies and camelid-derived nanobodies as biotherapeutic weapons against SARS-CoV-2 and its variants: A review article

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected 305 million individuals worldwide and killed about 5.5 million people as of January 10, 2022. SARS-CoV-2 is the third major outbreak caused by a new coronavirus in the previous two decades, following SARS-CoV and MERS-CoV. Even though vaccination against SARS-CoV-2 is considered a critical strategy for preventing virus spread in the population and limiting COVID-19 clinical manifestations, new therapeutic drugs, and management strategies are urgently needed, particularly in light of the growing number of SARS-CoV-2 variants (such as Delta and Omicron variants). However, the use of conventional antibodies has faced many challenges, such as viral escape mutants, increased instability, weak binding, large sizes, the need for large amounts of plasma, and high-cost manufacturing. Furthermore, the emergence of new SARS-CoV-2 variants in the human population and recurrent coronavirus spillovers highlight the need for broadly neutralizing antibodies that are not affected by an antigenic drift that could limit future zoonotic infection. Bovine-derived antibodies and camelid-derived nanobodies are more potent and protective than conventional human antibodies, thanks to their inbuilt characteristics, and can be produced in large quantities. In addition, it was reported that these biotherapeutics are effective against a broad spectrum of epitopes, reducing the opportunity of viral pathogens to develop mutational escape. In this review, we focus on the potential benefits behind our rationale for using bovine-derived antibodies and camelid-derived nanobodies in countering SARS-CoV-2 and its emerging variants and mutants.

Keywords: Antibodies; Bovine; COVID-19; Camelide; Nanobodies; Omicron; SARS-CoV-2; Vaccines; Variants.

Graphical abstract

Fig. 1

A. Four peptide chains, two identical heavy chains, and two light chains make up the entire 150 kDa IgG antibody (Conventional IgG antibodies). The antigen-binding sites are produced by the two variable domains (VL and VH), while the stem of the antibody molecule is generated by the constant Fc-region. B. Sera of camelids contain a unique functional heavy (H)-chain antibody (HCAbs) in addition to conventional antibodies. The VHH or nanobody (15 kDa), a single-domain antibody generated from HCAb, is the smallest available antibody fragment with functional antigen binding. HCAb is devoid of light chains and is capable of antigen recognition solely by one single domain, the variable heavy domain (VHH). Fab; fragment antigen binding, CL; light chain constant region, CH; heavy chain constant region, VL; light chain variable region. VH; heavy chain variable region, VHH; variable heavy domain, HCAbs; heavy (H)-chain antibody.

Fig. 1

A. Four peptide chains, two identical heavy chains, and two light chains make up the entire 150 kDa IgG antibody (Conventional IgG antibodies). The antigen-binding sites are produced by the two variable domains (VL and VH), while the stem of the antibody molecule is generated by the constant Fc-region. B. Sera of camelids contain a unique functional heavy (H)-chain antibody (HCAbs) in addition to conventional antibodies. The VHH or nanobody (15 kDa), a single-domain antibody generated from HCAb, is the smallest available antibody fragment with functional antigen binding. HCAb is devoid of light chains and is capable of antigen recognition solely by one single domain, the variable heavy domain (VHH). Fab; fragment antigen binding, CL; light chain constant region, CH; heavy chain constant region, VL; light chain variable region. VH; heavy chain variable region, VHH; variable heavy domain, HCAbs; heavy (H)-chain antibody.

Fig. 2

Using Cow-derived antibodies in combination with camelid nanobodies could be a powerful biotherapeutics in our armamentarium against SARS-CoV-2 and its emerging variants. It starts by immunizing TcBs and camelid thereafter collecting and isolating polyantibodies (pAbs) and heavy chain antibodies (HCAb), respectively. Consequently, the purification process is done which followed by pABs and VHH testing. Notably, Nanobodies could be used after fusion (Multivalent). Combining SAB-185, which is administrated intravenously, and nanobodies, which are administrated orally or by inhalation, could be a powerful synergism against SARS-CoV-2 and its emergent variants either detected or undetected yet.