The benefits of choosing rabbit monoclonal antibodies over regular monoclonal or polyclonal antibodies

Introduction

When it comes to identifying proteins in research or developing therapeutics for clinical use, antibodies have become uniquely placed as the most suitable option. Ever since Georges J.F. Khler and César Milstein first described the hybridoma technique for the production of monoclonal antibodies in 1974^1,2, antibodies have become indispensable to molecular biology and can be produced in several host species. However, the initial technique has since been modified with variations that meet multiple specific needs³. With the availability of multiple options, how do you decided whether a monoclonal or polyclonal antibody is right for your experiment? Why is it best to choose rabbit monoclonal antibodies over other regular monoclonal or polyclonal antibodies such as rat or mouse? To address this, let's first look at antibodies and why they are so vital to scientific and medical research.

What is an antibody

Antibodies are proteins secreted by B cells of the immune system to detect, bind and neutralise antigens unique to organisms such as viruses and bacteria. Antibodies are arguably the lifeline of scientific, clinical research and diagnostics due to their role in detecting and identifying antigens⁴. These antigens are usually proteins but can be nucleotides, small molecules or macromolecules. The ability of an antibody to efficiently bind an antigen depends on the binding sequence on the surface of the antigen, known as the epitope and how well the epitope matches the sequence on the binding surface of antibody.

Antibodies are structured as Y-shaped molecules where the tail end is responsible for the effector function and allows the interaction of the antibody with other cells of the immune system. Each arm of the Y has a variable region which is specific to recognising the epitope on an antigen. Read about our brief history of antibodies here.

The monoclonal / polyclonal antibody production technique depends on the ability to stimulate the B cells of a host species to continuously produce antibodies, which are subsequently harvested and purified for research and clinical use.

What is the difference between monoclonal and polyclonal antibody?

When an immunogen (antigen) is injected into an animal, the B cells of the primary immune response secretes different antibodies that recognise and bind to several epitopes on the antigen. As the antibodies secreted are produced by several plasma cells they are described as polyclonal antibodies.

Monoclonal antibodies on the other hand are engineered to be produced by the same B cells which are clones from a single parent cell. This means that the monoclonal antibodies can only recognise and bind to the same epitope of an antigen reducing the risk of cross reactivity.

Polyclonal antibodies are usually produced in vivo and monoclonal antibodies are produced ex vivo making them easier to be standardised. Although monoclonal and polyclonal antibodies have pros and cons for use as research tools, the heterogeneity nature of polyclonal antibodies limits their development, validation and use. Monoclonal antibodies are therefore generally preferred to polyclonal antibodies.

Visit our previous post for the advantages and disadvantages of monoclonal and polyclonal antibodies.

Why choose rabbit monoclonal antibody?

Monoclonal antibodies have traditionally been raised in rodents such as mice as it is cost effective and easier to manage. However, the use of rabbits as host species is increasingly becoming the preferred choice of monoclonal antibody for use in a wide range of research, diagnostics and clinical application as the immune system of rabbits is able to produce a wider range of high affinity antibodies, compared to mice. Rabbit monoclonal antibodies also produce better reaction to immunogens and have a higher affinity and specificity to the epitope. With antibodies raised in rodents, there is a higher chance of proteins being recognised as self-antigens making them less immunogenic. In addition, rabbits tend to be better at producing antibodies to smaller peptides with small-size epitopes that usually elicit a poor response in mice.

St John's laboratory has a range of rabbit monoclonal antibodies suited for your needs.

References

1. Alkan SS.The discovery of monoclonal antibodies (on Georges Khler). Allergy 2019. https://doi.org/10.1111/all.13798

2. Khler G, Milstein C.Continuous cultures of fused cells secreting antibody of predefined specificity.Nature. 1975; 256:495–497.

3. Carvalho, L.S., Silva, O.D., Almeida, G.D., Oliveira, J.D., Parachin, N.S. and Carmo, T.S., 2017. Production Processes for Monoclonal Antibodies.Fermentation Processes, pp.182-198.

4. Brekke, O.H. and Sandlie, I., 2003. Therapeutic antibodies for human diseases at the dawn of the twenty-first century.Nature reviews Drug discovery, 2(1), p.52.