Alpaca nano antibody

Novel coronavirus is still widely spread around the world, with the cumulative number of infected people exceeding 250 million and the death toll exceeding 5 million 1. Although all kinds of vaccines have been widely promoted, they still failed to stop the spread of COVID-19 epidemic. Moreover, with the development of the epidemic, COVID-19 is constantly changing, which has brought heavy disasters to all countries in the world. Effective prevention and treatment is the key to the complete elimination of COVID-19. Nano-antibodies derived from alpaca have been proved to have great application potential in the prevention and treatment of coronavirus (table 1).

Table 1. Study on prevention and treatment of nano-antibody in COVID-19

The origin of nano-antibody:

Nano-nano-body (Nbs) was first reported by Belgian scientist Hamers-Casterman and his team in 1993 in the journal Nature. It was found that some antibodies in the blood of camels (camels, alpacas and their close relatives) are "heavy chain antibodies" lacking light chains, and only contain one heavy chain variable region (VHH) and two heavy chain CH 2 and CH 3 regions (CH2 and CH3). VHH retains all the antigen binding ability and is the smallest complete antigen binding fragment, which is called single domain antibody. VHH crystal is 2.5 nm and 4 nm long, and its molecular weight is only 15 kDa.

Figure 1. Schematic diagram of conventional antibodies and nano-antibodies.

Advantages of nano-antibody over traditional antibody;

Compared with traditional antibodies, nano-antibodies also have the advantages of simple humanization, high affinity, high stability, microbial expression, low immunogenicity, good solubility, strong penetration and recognition of hidden epitopes. The unique physical and chemical stability of nano-antibodies provides a new research tool for diagnosis and treatment. More and more attention has been paid to the research and development of antibody drugs, basic medical research and disease diagnosis and treatment.

Nano-antibody drugs approved for global marketing:

In 20 18, the European union approved-the world's first nano-antibody drug Caplacizumab for treating adult acquired thrombotic thrombocytopenic purpura, which prevents coagulation by blocking the interaction between oversized vWF polymer and platelets. In 20021year, PD-L 1 Antibody Envida, jointly developed by Corning Jerry Pharmaceutical, Sildi Pharmaceutical and Voice, was approved for listing in China, which was the first nano-antibody drug approved for listing in China. At present, many nano-antibody drugs are in the clinical trial stage (Table 2).

Table 2. Nano-antibody drugs in clinical stage

Preparation process of nano-antibody;

The preparation process of nano-antibody mainly includes preparation of target antigen, immunization of alpaca, preparation of antibody library, screening of high affinity antibody, expression of recombinant antibody and functional identification of antibody activity analysis (Figure 2).

Figure 2. Preparation technology of nano-antibody.

Application of nano-antibody;

1. Disease diagnosis: molecular imaging, tumor diagnosis, image-guided surgery.

2. Cell therapy: targeted radiotherapy, chemotherapy drug delivery, immunotherapy.

3. Research and development of antibody drugs: finding targets → designing drugs → biological trials → clinical trials → approval for marketing.

References:

1.? Nano-antibody functionalized cellulose for capturing novel coronavirus. Applied environmental microbiology. 2022 1 5th of May: AEM 0230321doi:10.128/AEM.02303-21. Epub before printing. PMID: 34985974。

2.? Structural basis of effective neutralization of β -coronavirus by single domain camel antibody. Cells. May 28, 2020; 18 1(5): 1004- 10 15 . e 15。

3.? Wu Yan, Li Chun, et al. Identification of human anti-novel coronavirus single domain antibody. Cell host microorganism. June 202010; 27(6):89 1-898.e5。

4.? Huo j, lebas a,? Neutralizing nanoantibody binds to novel coronavirus RBD and blocks the interaction with ACE2. Molecular biology of natural structures. September 2020; 27(9):846-854.

5.? An alpaca nano antibody neutralizes novel coronavirus by blocking receptor interaction. National community. September 4, 2020; 1 1( 1):4420.

6.? Multifunctional multivalent nano antibody can effectively neutralize novel coronavirus. Science. 20201February 65438 +08; 370(6523): 1479- 1484.

7.? A synthetic nanoantibody with super ability neutralizes novel coronavirus by stabilizing inactive spikes. Science. 20201February 65438 +08; 370(6523): 1473- 1479.

8.? Effective neutralizing nano-antibodies resist novel coronavirus's convergent circulating variants by targeting different and conservative epitopes. Nat Commun 12,4676 (202 1)。

9.? An effective bispecific nano-antibody can protect hACE2 mice from novel coronavirus infection by intranasal administration. Cell representation 2021oct19; 37(3): 109869.

10.? Rapid and affordable point-of-care detection of anti-novel coronavirus antibody based on hemagglutination and artificial intelligence interpretation. Science report 20211February 30th; 1 1( 1):24507.

1 1.? Nanometer? A new weapon against viruses. Antiviral research 2011dec; 92(3):389-407.?

Editor: Zhang Taotao