Venezuelan equine encephalitis (VEE) is a significant viral disease caused by the Venezuelan equine encephalitis virus (VEEV). Our comprehensive services in VEEV vaccine and therapeutics development encompass the full spectrum of research and development activities.
Overview of Venezuelan Equine Encephalitis Virus Infection
Venezuelan equine encephalitis virus (VEEV) is an alphavirus from the Togaviridae family that has one type of vector - a mosquito which is already infected. It is well known that the first stage of this infection causes febrile illness followed by severe complications which might include inflammation of the brain's tissue. VEEV is commonly found in Central and Southern America, with occasional outbreaks resulting in increased suffering for both humans and equines. Infection generally sets in after 5 days of incubation, showing symptoms of fever, headache, and gastro-internal distress. Moreover, extreme patients may undergo seizures, changes in behavior and consciousness, as well as other neurological complications which are seen in 14% of all those infected.
Fig.1 Transmission of Venezuelan equine encephalitis virus (VEEV). (Sharma A., et al., 2019)
Vaccine Development for Venezuelan Equine Encephalitis Virus Infection
- Live-Attenuated Vaccines
Live-attenuated vaccines have played a significant role in controlling VEE. These vaccines employ an altered (weakened) form of the virus that is unable to cause any disease but can still prompt an immunological response.
- Inactivated Vaccines
One of the shortcomings of inactivated vaccines is that long-lasting immunity is difficult to achieve, and they require additional adjuvants to achieve an increase in their immunogenicity.
- Recombinant Vaccines
In VEEV vaccine development, the application of recombinant technology has been a game-changer. Vaccines that target certain viral proteins can be manufactured to focus the immune response against them.
- DNA Vaccines
The DNA vaccine is the most advanced option available. The vaccine comprises a genetic construct that encodes the relevant antigens for VEEV. After administration, the host's cells will synthesize the antigen, which will bring about an immune response. This approach renders any live viruses unnecessary, thereby eliminating the risk of reversion to virulence.
Table 1 VEEV vaccine candidates. (Sharma A., et al., 2019)
Vaccine Type |
Strain/Antigen |
Immunity |
Status |
Live-attenuated |
TC-83 |
Sterile |
IND |
V3526 |
Sterile |
Phase I |
Inactivated |
Formalin inactivated TrD |
Sterile |
Equine vaccine (discontinued) |
Formalin inactivated C84 (TC-83) |
Poor immunogenicity |
IND (Booster) Veterinary vaccine |
INA-inactivated V3000 and V3526 |
Sterile |
Pre-clinical |
Gamma-irradiated V3526 |
Sterile |
Pre-clinical |
Chimera |
VEEV/mutSG/IRES/1 (TC-83) |
Sterile |
Pre-clinical |
VEEV/IRES/C (TC-83) |
Sterile |
Pre-clinical |
VEEV/IRESv1 (68U201) VEEV/IRESv2 (68U201) |
Sterile |
Pre-clinical |
VEEV/IRES-Cm (TC-83) |
Sterile |
Pre-clinical |
SINV/VEEV (TC-83) |
Non-sterile |
Pre-clinical |
SINV/VEEV (TrD) |
Non-sterile |
Pre-clinical |
SINV/VEEV (ZPC738) |
Non-sterile |
Pre-clinical |
EILV/VEEV (TC-83) |
Sterile |
Pre-clinical |
EHV-1/VEEV (TC-83) |
Sterile |
Pre-clinical |
MVA-BN/VEEV (TrD) |
Sterile |
Pre-clinical |
Subunit |
pWRG7077/VEEV (TrD structural genes) |
Non-sterile |
Pre-clinical |
pWRG7077/VEEV (TrD envelope genes) |
Sterile |
Phase I |
pWRG7077/VEEV (TrD Structural genes with T-cell epitope optimized) |
Sterile |
Pre-clinical |
pWRG7077/VEEV (TrD and IE E2) |
Sterile |
Pre-clinical |
pcDNA3.1/VEEV (TC-83) |
Non-sterile |
Pre-clinical |
LANAC (TrD E1) |
Sterile |
Pre-clinical |
Replicon particles |
VEEV VRP (V3000 E2 and E1) |
Non-sterile (6h before challenge) |
Pre-clinical |
Rad/VEEV (TrD E2) |
Sterile |
Pre-clinical |
Rad/VEEV (TC-83 E2) |
Sterile |
Pre-clinical (Booster) |
V3014 VRP (V3014 PE2 |
Sterile |
Pre-clinical |
Passive |
1A4A-1 Hu1A4A1IgG1-2A |
Sterile (Prophylactic) Non-sterile (Therapeutic) |
Pre-clinical |
Hu Mab F5nIgG |
Non-sterile |
Pre-clinical |
Hu1A3B7 (E2) |
post infection |
Pre-clinical |
13D4 (Anti-E3) |
Non-sterile |
Pre-clinical |
CUF37-2a (Anti-E2) |
Non-sterile |
Pre-clinical |
3B4C-4, Hu Mab Hy4-26C |
Non-sterile |
Pre-clinical |
Therapeutics Development for Venezuelan Equine Encephalitis Virus Infection
Anti-Inflammatory Drugs
The management of VEEV is aided through inflammation-eliminating therapies that are launched after the infection has occurred. The COX-2 inhibitor celecoxib has shown significant decrease of virus titer and inflammation in vivo. Such strategies may prove critical in lessening the neurological damage so prevalent with VEEV.
Direct Antiviral Therapies
Direct antiviral drugs (DAAs) are being studied for their ability to inhibit viral replication. These agents act on particular enzymes or stages of the viral life cycle and thought to achieve a greater control over the disease.
Immunomodulatory Therapies
Certain strategists detach the immune response from the host and are also under investigation. These therapies focus on improving the immune system response towards VEEV and thereby, strengthen the viral clearance of the body while controlling the harmful effects of the disease.
Our Services
The area of developing highly efficacious vaccines and therapeutics aimed at Venezuelan equine encephalitis virus infection is a rapidly changing area. Our company offers a specialized and novel range of services which are tailored for the development of VEEV vaccines and therapeutics. We have an experienced team of specialists capable of overseeing the entire process from development to the preclinical stages of the research.
- VEEV Aerosol Infection BALB/c Mouse Models
- VEEV Intranasal Challenge C3H/HeN Mouse Models
- VEEV Infection in Non-human Primates (NHPs) Models
Within our preclinical research realm, we boast a diverse range of capabilities, including:
- Molecular Biology: Gene cloning, expression, and analysis of viral proteins.
- Immunology: Assessment of immune responses to candidate vaccines and therapies.
- Virology: Isolation and characterization of VEEV strains for research purposes.
- Pharmacology: Evaluation of drug efficacy and safety in relevant models.
If you are interested in our services, please feel free to contact us.
References
- Sharma, Anuj, and Barbara Knollmann-Ritschel. "Current understanding of the molecular basis of Venezuelan equine encephalitis virus pathogenesis and vaccine development." Viruses 11.2 (2019): 164.
- Risner, Kenneth, et al. "Efficacy of FDA-approved anti-inflammatory drugs against Venezuelan equine encephalitis virus infection." Viruses 11.12 (2019): 1151.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.