Venezuelan Equine Encephalitis Virus Vaccine
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Venezuelan Equine Encephalitis and Its Causative Agent
Venezuelan equine encephalitis (VEE) is an acute flu-like disease caused by Venezuelan equine virus (VEEV). Patients infected with VEEV may have fever, headache, and muscle pain, and the condition may further develop into encephalitis. The VEE epidemic has infected thousands of people and horses. The disease was first discovered in central and southern America and has now spread to the United States and has become a serious threat to the American people. The first confirmation of VEE was in Venezuela in 1938, and the first case of human infection with the virus was in 1943 in a laboratory for the identification of equine isolates. The first extensive Venezuelan equine encephalitis outbreak occurred in 1995. A total of 75,000 people were infected in Colombia and Venezuela, and 300 people died and 50,000 horses were infected with a mortality rate of 8%. Symptoms are usually mild when human infected with VEEV and may last for 3-5 days. Children are at high risk to develop central nervous system damage such as encephalitis once contracted with Venezuelan equine encephalitis virus.
Venezuelan equine encephalitis virus belongs to the genus Alphavirus in the Togaviridae family. Genome of the virus is a positive-strand and unsegmented RNA. The nucleocapsid of the virus is an icosahedron, which is coated with a lipid membrane on the outside, and glycoproteins E1 and E2 are inserted on the lipid membrane. E2 is a major factor in the adhesion of virus to the surface of recipient cells, and antibodies against E2 could neutralize infection of the virus. The serotypes of ID, IE, and IIIA of Venezuelan equine encephalitis virus are not pathogenic to horses but can cause disease in humans. Venezuelan equine encephalitis virus is an arthropod-borne virus and its main vector are mosquitoes. The virus can be found in birds, rodents, bats, and horses. Horse plays an important role in amplifying the virus in the large outbreaks of the virus.
Immune Responses for Protection against VEEV Infection
Studies have shown that the production and level of neutralizing antibodies is the key for immune system to defend and protect bodies resistant to VEEV infection. Recently, research has shown that even high titer polyclonal neutralizing antibodies prepared by passive transfer cannot protect mice against intranasal challenge by lethal VEEV in the mouse model. Current data suggest that neutralizing antibodies can prevent peripherally challenged VEEV from penetrating into the central nervous system but are relatively ineffective in controlling the development of central nervous system diseases caused by intranasal infections.
For cell-mediated immune response, T cells are divided into CD8+ cytotoxic cells and CD4+ helper cells. In T cell populations, αβ T cells occupy a large proportion. Studies in TC83-vaccinated mice show that Th1-type immune response is dominating in protecting mice against VEEV challenge. Besides, no cytotoxic T cell activity was detected in the spleen or lymph nodes of mice parenterally immunized with TC83. Other studies suggest that functions of CD4+ T cells in encephalitis are combined of activities of Th1, Th2, and regulatory T cells. Results from some encephalitis models also manifest that myelin basic protein-specific CD4+ T cells are of significant importance in the development of the encephalitis. There is a hypothesis that the role of cell-mediated cytotoxicity in controlling VEEV infection is less critical than controlling infections caused by noncytopathic viruses. Therefore, it is believed that the CNS eliminates viruses in neurons through a non-lytic mechanism because of the weak regenerative ability of CD8+ T cells there.
Development of the Venezuelan Equine Encephalitis Vaccine
- Live-attenuated VEE vaccines
TC-83 vaccine is an attenuated VEE vaccine prepared by 83 sequential passages in heart cells of guinea pigs. The vaccine successfully limited the spread of the VEE epidemic in Texas to the north in 1971. Although the vaccine can cause adverse reactions such as viremia and fever after immunization, the high-intensity neutralizing antibody it induced is sufficient to protect horse against VEEV challenge. Therefore, the vaccine is still circulated in the US market in inactivated form (C-84). With the threat of VEEV being used as a biological weapon, TC-83 is prompted to be applied in human. Another attenuated vaccine V3526 is much safer and performs better in rodents than TC-83, and the vaccine is less possible to transmit and distribute in the environment, and there is no neurotoxicity in intracranial immunization of rhesus macaques.
- Inactivated VEE Vaccines
The earliest vaccine for VEE is formalin-inactivated virus prepared from animal tissues injected with wide-type VEE strains isolated from epizootics. Such vaccines are efficacious but, in some conditions, incomplete inactivation or escape of VEE from being inactivated may cause severe outcomes. At present, commercial used VEE vaccines in the US is inactivated TC-83 combined with other alphaviral encephalitides.
- Sindbis Virus-based Chimeric Vaccine
Sindbis virus (SINV) is a nonpathogenic alphavirus and is designed to be a vector to express antigens of virulent alphavirus. Results from mouse model show that chimeric SIN/VEE is highly efficacious and safer than TC-83. It has also been found that antibody may be not essential for protection against lethal VEE.
- Alphavirus Replicons
Genes of structural protein in alphavirus genome can be replaced by genes of foreign antigens, therefore such replicon genomes can be packaged into VLP in the aid of a second genetic construct. These replicons can be used to induce immune response against heterologous or homologous alphavirus and do not need to worry about the safety issues associated with live viruses, and because of the RNA replication activity of the replicons, they have systemic and mucosal adjuvant activity.
- DNA Vaccines
A DNA vaccine that expresses envelope glycoproteins of VEEV shows high immunogenicity and complete protection in mice and the neutralizing antibodies it induced could maintain high level for at least 6 months in rabbit, besides, efficacy is also observed in cynomolgus macaques. Recent studies further indicate that directed molecular evolution could improve effectiveness of alphavirus DNA vaccines both in immunogenicity and protectiveness.
Creative Biolabs is a trusted vaccine development and service-providing company. Since its establishment more than ten years ago, the company has always been improving itself to meet the highest standards, constantly grasping the latest developments and technologies of the world vaccine industry, and unremittingly expanding and perfecting its service system. Now we have built a comprehensive and mature vaccine research and development service system. In terms of VEE vaccine, we have a complete research and development system, can design and prepare various types of VEE vaccines with good effects, and we can provide various services related to this. No matter how many problems and needs you have, it is your wisest decision to contact us.
All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.
