Creative Biolabs has launched a novel service of Simianization of Non-monkey Antibodies.
In comparison with rodents and rabbits, monkeys (NHPs) are large animals with a genetic background closer to that of humans. Monkey versions of monoclonal antibodies are of paramount value in evaluating a therapeutic antibody in monkey (NHP) animal models. Relying on our years of experience in antibody humanization and phage display antibody library technologies, scientists of Creative Biolabs have built up a platform to covert non-monkey monoclonal antibodies into monkey antibodies, which is so called antibody simianization. This service is mainly achieved by CDR grafting followed by phage display antibody library based back mutation. Monoclonal antibodies derived from a variety of species, such as human, rabbit, chicken, mouse, rat, dog and cow, can be converted into simian antibodies using the same approach. Antibody specificity and affinity are well preserved after simianization.
Fig. 1 Genotyping, immune response and preferential TCR Vβ usage of immunized Aotus monkeys. (Patarroyo et al. 2010)
Currently, Creative Biolabs is the sole resource that offers this cutting-edge service.
Other optional antibody engineering services:
Fig. 2 Structure-guided simianization of VRC01. (Kevin O. Saunders, 2015)
Anti-human immunodeficiency virus (HIV) antibodies may be a potential drug that can prevent HIV infection in humans. However, it is unclear whether anti-HIV antibodies can protect capable non-human primates (NHP) from lentivirus infection over the long term. Here, researchers repeatedly injected monkeys with simianized human anti-HIV antibodies and found that the antibodies persisted in the blood for more than five months. In addition, in a monkey model of HIV infection, two months after the last antibody administration, the animals were completely protected from virus attack. It was concluded that passive antibody transfer could provide primates with long-term protection from HIV infection.
Antibody simianization is a specific form of antibody humanization used primarily for therapeutic purposes in non-human primates. This process involves altering the molecular structure of an antibody originally developed in another species (like mice) to reduce immunogenicity and improve pharmacokinetics when used in primate models.
The process typically involves replacing certain regions of the mouse antibody with analogous sequences from a primate antibody. Key areas targeted include the framework regions of the variable domains of the antibody, while retaining the original mouse antigen-binding sites (CDRs). This helps maintain the antibody's specificity and affinity for its target antigen while reducing its foreignness to the primate immune system.
As with any biological therapy, there is a risk of immune responses, even with simianized antibodies. Although simianization reduces the likelihood of immune reactions, it does not completely eliminate the risk. Ongoing research aims to further refine this process to increase safety and efficacy for use in both preclinical and clinical settings.
While both processes aim to modify antibodies to reduce immunogenicity in a new host, simianization modifies antibodies for compatibility with non-human primates, whereas humanization is done for human compatibility. Simianization may retain more of the original non-primate sequences compared to humanization, focusing on adaptations that specifically address the immune system of the target primate species.
Simianized antibodies can play a crucial role in the development of vaccines by providing a model to study immune responses and antibody efficacy in primate systems that are physiologically closer to humans than other animal models. This can be particularly important for diseases that are unique to primates or where a human-like immune response is crucial for testing the vaccine's effectiveness.
While simianized antibodies are primarily designed for research involving non-human primates, insights gained from these studies can inform the development of humanized antibodies. Direct therapeutic applications in humans are unlikely due to the potential for immunogenicity, but the data obtained from simianized antibody studies can be invaluable in designing more effective human treatments.
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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.