The Rabies is one of the most dangerous infections of the nervous system, caused by a virus and has an overall 100% fatality rate if it goes untreated. 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 is known to be one of the most horrific viral infections of the central nervous system which can be extremely fatal for a range of mammals along with human beings as well. The disease is caused by a particular virus, the rabies virus (RABV), which is further classified under the genus of Lyssavirus within the Rhabdoviridae family. A negative-sense, single-stranded RNA virus, RABV is an animal-borne disease that is spread most commonly through dogs and any other infected creatures that bite.
The process starts when the infected animal bites someone whereas the virus enters the body of the victim, the RABV makes its way through the peripheral nervous system in a gradual preference of reaching the central nervous system (CNS), instigating inflammation that leads to impairment of proper functioning. Some of the primary symptoms of rabies include fever, headache, uneasiness, anxiety, confusion, restlessness, hallucination, paralysis, coma etc, which alongside difficulty in swallowing and over salivation worsen dramatically if rabies is not treated in time.
Fig.1 Schematic representation of the rabies virus genome. (Smith S. P., et al., 2019)
Vaccine Development for Rabies
- Live-Attenuated Viruses
The orthodox technique of administering live-attenuated rabies vaccines have been integral to inhibiting outbreaks and disease prevalence. This method can incorporate strains of rodents that have been cultivated for their pathogenic features but still have the capability of mounting immune response. Examples include SAD B19 and ERA strains which have found their way into veterinary practice.
- Inactivated Virus Vaccines
Efforts to make the rabies vaccine safer led to adopting a strategy of using inactivated viruses. Treating the virus to render them incapable of replication and propagation, while still retaining their immunogenic features, renders a safer alternative. This has been widely adopted in vaccines for humans, one of them being the purified Vero cell rabies vaccine (PVRV), which is cultivated inside Vero cells and then made inactive.
- Recombinant Vaccines
Advancements in DNA technology has paved the path for developing antigen-encoding vaccines. Certain vaccines fall under the DNA vaccine category and others are viral vector vaccines which incorporate a harmless virus carrying the gene for RABV glycoprotein. An example of this is recombinant adenovirus type 5 (HAdV-5) vaccine which is currently undergoing preclinical trials and has exhibited encouraging results.
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 as a therapeutic modality has an important place in viral diseases including rabies. There is a specific siRNA that can silence target genes, therefore, interrupting the progression of the disease while utilizing the RNA interference (RNAi) pathway. Earlier efforts used plasmids that encoded for siRNA that targeted conserved genes N and L of RABV.
Monoclonal Antibodies
RABV specific immunoglobulin (RIG) is a modified form of monoclonal antibodies (mAbs) that prevent the RABV from spreading to the central nervous system. The combination of RIG and the augmentation of BBB permeability enables the implementation of a new viable therapeutic strategy. Such methods significantly improve RIg circulation and utilization within the CNS for effective viral neutralization. The MCP-1 agents mentioned earlier helped tremendously in the transport of antibodies into the CNS.
Bi-Specific Antibodies
Bi-specific antibodies (BsAbs) are receiving much attention as a new weapon in the arsenal of immunotherapy. These antibodies can bind to two different antigens at the same time. With regards to rabies, BsAbs could be developed to bind to a BBB receptor and to the RABV G protein, an approach aimed at delivering neutralizing antibodies directly where they are most needed, in the central nervous system.
Our Services
Our company is a leader in rabies vaccine and therapy development services. Using the experience of veteran scientists and state of the art infrastructure at our disposal, the following services are offered:
- 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.
