The benefits of generating antibodies in rabbits, as opposed to more traditional species like mice or rats are truly endless. First and foremost, rabbits are able to generate highly specific antibodies due to their enhanced means of B cell maturation. Rather than relying on common mechanisms of gene conversion and somatic hyper mutation, immature rabbit B-cells also go through a complex gene conversion-like mechanism for sequence development. This enhanced maturation process allows for the development of longer and more heterogeneous complementarity-determining regions (CDRs) than those commonly produced in mice or humans. Secondly, the rabbits immune system is capable of eliciting a strong immune response against small, non-amino acid antigens, which are either non-immunogenic in mice or mount a weaker response in mice than in rabbits. As a result, rabbit mAbs can easily recognize phospho-peptides, carbohydrates, haptens, and small molecules. Third, the evolutionary distance between human and rabbit is farther than the one between human and mouse. As a result, rabbits can recognize a larger number of targetable epitopes compared with mice and, therefore, can generate antibodies capable of cross-reacting with mouse orthologs of human antigens. This in turn avoids the issue of self-antigen recognition occurring in the application of an antibody. Fourth, compared to human and mouse, rabbit immunoglobulins have a simpler and more stable structure. In addition, rabbit IgGs contain fewer amino acids at their N terminal and D-E loop as well as extra disulfide bonds in the variable region of their heavy chain. These characteristics are suggested to render rabbit Abs more stable and, therefore, easier to work with.
Rabbit antibodies make great reagents for everything from basic research through to therapeutic antibody discovery. Some applications which require the high specificity, affinity, and sensitivity of rabbit antibodies are diagnostics, pharmacokinetics, and therapeutics. In terms of diagnostics, rabbit mAbs enable the development of a wide range of in vitro and in vivo diagnostics. A variety of IVD assays, such as IHC, ELISA, and radio immunoassays (RI) are based on the principles of antigen-antibody binding. Given the critical role of these assays in patient or animal care, it is extremely important that IVD assays are carried out using the highest sensitivity and affinity mAbs available. In drug development, pharmacokinetic (PK) assays are used to measure the absorption and excretion rates, distribution, and half-life of candidate small molecules or mAb therapeutics. High sensitivity and specificity rabbit mAbs are, hence, useful reagents in PK studies for obtaining accurate quantitative measurements of a drug’s concentration with no worries about false positive or negative results. For therapeutics, specificity and sensitivity of an antibody towards its target antigen ensure both safety and toxicity concerns: highly specific antibodies avoid off-target binding and hence, offer safety; highly sensitive antibodies require low dosage administration and hence, cause a minimum level of toxicity. Given that rabbit mAbs have both of these sought-after characteristics, they are considered as excellent therapeutic candidates in order to directly target disease-specific cell surface antigens or used as cytotoxic drug delivery agents. Rabbit antibodies are also highly effective in generating single chain variable fragment (ScFv) antibodies for Chimeric Antigen Receptor Antigen T-Cell therapy (CAR-T).