Rabies is a lethal viral disease affecting the central nervous system, with an incidence rate that is a significant public health concern globally. As a leading provider of rabies vaccine and therapy development services, our company is committed to advancing the field and addressing the significant unmet need in this area.
Introduction to Rabies
Rabies stands as a grave and frequently lethal viral illness impacting the nervous system of various mammals, humans included. The responsible pathogen, the rabies virus (RABV), is categorized under the Lyssavirus genus within the Rhabdoviridae family. RABV, a negative-sense, single-stranded RNA virus, predominantly transmits through bites from infected animals, with dogs being the most common carriers.
Upon entry into the body, the virus navigates through the peripheral nerves towards the central nervous system (CNS), instigating inflammation and functional impairment. Untreated, rabies proves nearly 100% fatal, solidifying its status as one of the most lethal infectious diseases witnessed by humankind. Initial symptoms usually manifest as fever, headache, and overall unease, advancing to anxiety, confusion, restlessness, hallucinations, excessive salivation, swallowing difficulties, and ultimately leading to paralysis and coma.
Fig.1 Schematic representation of the rabies virus genome. (Smith S. P., et al., 2019)
Vaccine Development for Rabies
- Live-Attenuated Viruses
Live-attenuated rabies vaccines have been instrumental in the prevention of the disease. These vaccines are created by modifying the virus to reduce its pathogenicity while retaining its ability to elicit a strong immune response. Examples include the SAD B19 and ERA strains, which have been used extensively in veterinary applications.
- Inactivated Virus Vaccines
Inactivated virus vaccines offer a safer alternative by using viruses that have been treated to destroy their ability to replicate while maintaining their antigenic properties. This approach has been widely adopted in human vaccines, such as the purified Vero cell rabies vaccine (PVRV), which is produced by growing the virus in Vero cells and then inactivating it.
- Recombinant Vaccines
Recombinant DNA technology has facilitated the development of vaccines that encode specific viral antigens. These vaccines include DNA vaccines, such as pGPV, and viral vector vaccines, which use a harmless virus to carry the gene for the RABV glycoprotein. An example is the recombinant adenovirus type 5 (HAdV-5) vaccine, which has shown promising results in preclinical trials.
Table 1 Current research status of rabies vaccines. (Natesan K., et al., 2023)
|
Vaccines |
Vaccine Name |
Research Focus |
Research Outcomes |
| Modified Live rabies vaccine |
ERA-G333 Leu |
Arg-to-Leu mutation at G333 using reverse genetics in ERA strain |
Increased neutralizing antibody response and protective immunity in 6-week-old mice and increased their survival rate |
| Inactivated rabies Vaccine |
- |
Vero Cell Rabies Vaccine
Inactivated and stabilized using different inactivating compounds |
Increased IgG levels |
| Adjuvanted rabies vaccine |
- |
Effect of adjuvanticity β-glucans on inactivated rabies vaccine |
Amplified adaptive immune response |
| Nuclei based acid rabies vaccine |
RG SAM (CNE) |
Assessed the rabies self-amplifying mRNA vaccine in rats |
Increased immune response in rats |
| Recombinant vaccines |
NC8-pSIP409-dRVG |
As a new oral rabies vaccine, recombinant Lactobacillus plantarum NC8 delivers one or two copies of G protein linked with a DC-targeting peptide (DCpep) |
The NC8-pSIP409-dRVG could protect 60% of inoculated mice against deadly RABV challenge, even though the titers of RABV neutralizing antibody (VNA) were less than the threshold of 0.5 IU/mL |
| Viral vector vaccines |
rAAV-G |
AAV-expressed G protein |
Encouraged production of durable RVNAs in mice |
| Intra Dermal Vaccines |
- |
Inactivated cell culture rabies vaccine administration viaSC, IM, and ID in dogs |
ID was found to be safe and immunogenic in dogs |
Therapeutics Development for Rabies
Small Interfering RNA (siRNA) Therapies
siRNA therapies represent a promising approach to viral diseases, including rabies. By harnessing the RNA interference (RNAi) pathway, siRNA can silence specific viral genes, effectively halting the disease progression. Early attempts utilized plasmids encoding siRNA to target conserved RABV genes, such as N and L.
Monoclonal Antibodies
RABV-specific immunoglobulin (RIG) is a form of mAb that neutralizes the virus before it reaches the central nervous system. The use of RIG, coupled with the enhancement of blood-brain barrier (BBB) permeability, presents a viable therapeutic strategy. This involves the use of agents like MCP-1 to facilitate the passage of antibodies into the CNS, ensuring effective viral clearance.
Bi-Specific Antibodies
Bi-specific antibodies (BsAbs) are emerging as a novel therapeutic modality in the field of immunotherapy. BsAbs have the unique ability to engage two different antigens simultaneously. In the context of rabies, BsAbs could be engineered to target both a BBB receptor and the RABV G protein, enabling the delivery of neutralizing antibodies directly to the virus's site of action in the CNS.
Our Services
At the forefront of rabies vaccine and therapy development, our company delivers a wide range of services to bolster clients' research and development endeavors. Leveraging the expertise of seasoned scientists and cutting-edge facilities, the following services are provided:
- Intracerebral Injection RABV Mouse Models
- Intraocular Injection RABV Rabbit Models
- Sciatic Nerve Injection RABV Dog Models
Other Species: Guinea Pigs, Rats, Hamsters, Non-human Primates
In addition to our vaccine and therapy development capabilities, our company offers a comprehensive suite of rabies-specific preclinical research services to support the entire drug development pipeline. If you are interested in our services, please feel free to contact us.
References
- Smith, Samuel P., et al. "Trying to treat the untreatable: experimental approaches to clear rabies virus infection from the CNS." Journal of General Virology 100.8 (2019): 1171-1186.
- Zhu, Shimao, and Caiping Guo. "Rabies control and treatment: from prophylaxis to strategies with curative potential." Viruses 8.11 (2016): 279.
- Fooks, Anthony R., Ashley C. Banyard, and Hildegund CJ Ertl. "New human rabies vaccines in the pipeline." Vaccine 37 (2019): A140-A145.
- Natesan, Krithiga, et al. "Developments in rabies vaccines: the path traversed from Pasteur to the modern era of immunization." Vaccines 11.4 (2023): 756.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
