Rabies mRNA Vaccines

Rabies is a zoonotic viral disease caused by the neurotropic rabies virus (RABV). Rabies can infect a variety of mammals, including humans, dogs, foxes, raccoons, and bats. It is an invariably fatal neurological disease. Once clinical symptoms are apparent, the results are nearly always fatal. Due to the limitations in their production capacities, cost, as well as requirements of administration schedules and storage, the current rabies vaccines can’t meet the global need for effective and affordable vaccines. Here, we focus on the mRNA vaccines developed against rabies.

Rabies

Rabies is caused by the neurotropic rabies virus (RABV), which is a single-stranded RNA virus of the Lyssavirus family. A variety of mammalian vectors carry this virus, such as humans, dogs, foxes, raccoons, and bats, and approximately 95% of human infections are due to dog bites. There is an incubation phase after exposure and followed by the development of influenza-like symptoms and severe neurotropic symptoms, finally leading to death. Because of the high cost of current rabies vaccines, their accessibility is limited. Rabies is now prevalent in the middle- and low-income countries where the virus is carried by dogs.

The genome of the rabies virus is relatively simple, which encodes five structural proteins, including nucleoprotein (N), glycoprotein (G), phosphoprotein (P), RNA polymerase (L), and matrix protein (M). Among these structural proteins, the envelope glycoprotein has been applied to induce virus-neutralizing antibodies and its protection has been proved in animal models.

Illustration of rabies virus genome and its common animal reservoir. (Ananda, R. A., et al, 2020)

Application of mRNA technology to rabies

There are several factors to favor rabies mRNA vaccine development. First of all, the genome of the rabies virus is simple. The envelope glycoprotein (RABV-G) as the target antigen of the immune response is well characterized. Second, rabies mRNA vaccine candidates can be readily tested and compared with other rabies vaccines, owing to the access to licensed and commercial rabies vaccines as well as the validated standardized tests for the measurement of RABV-G antigen immune response. Besides, the availability of a WHO-accepted threshold of protection based on the functional immune response can accelerate clinical development.

CV7201, an mRNA rabies vaccine candidate, consists of an optimized non-replicating RABV-G mRNA sequence and the cationic protein protamine. Compared with licensed rabies vaccines, this vaccine managed to elicit T cell responses, including CD4+ and CD8+ T cells. Subsequently, an mRNA vaccine with thermostability is developed against RABV, which brings the hope for addressing epidemic threats in tropical countries and economical vaccine stockpiling. As the first mRNA rabies vaccine against RABV, CV7201 is reported as generally safe with a reasonable tolerability profile in a clinical trial. Additionally, a recent study focuses on the co-administration of RNA-based adjuvant CV8102 with a licensed vaccine for rabies. The results of the Phase I clinical trial showed that CV8102 significantly enhanced the immunogenicity of the licensed rabies vaccine. To develop safe, effective, and affordable rabies mRNA vaccines (mRNA vaccine alone or as adjuvant), there is still much work to do for prevention and/or treatment regime.

Creative Biogene is a leading custom service provider in mRNA-based drug research and development (R&D). We are committed to exerting the potential of synthetic mRNA as an important vaccine candidate for infectious diseases, hoping to meet our customers' specific requirements for projects at the preclinical stages. If you are interested in this area, please feel free to contact us. We look forward to providing services for your next project.

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