Smallpox Vaccine

Creative Biolabs is a highly specialized company engaged in vaccine development and provision of related technical services. Our team has top scientists from all over the world, mastering cutting-edge science and technologies, and with accumulated decades of advanced experience. The company has a comprehensive and well-established research and development platform and can provide one-stop, all-round services from pre-design, process control to GMP production. We also have a mature R&D and production system for the development of smallpox vaccines, which can provide you with the most effective and economical services.

Variola Virus

Variola virus is the pathogen of acute, infectious disease smallpox, belonging to the Orthopoxvirus genus, Poxviridae family. The virus is large, brick-shaped, and the genome is double-stranded DNA which can also serologically cross-reacts with other members of the family of Poxviridae. Unlike other DNA viruses, variola virus replicates in the cytoplasm of host cells. Variola viruses usually only infect humans and there is no carrier status. There are two main types of variola virus, major and minor. The mortality rates of these two viruses vary greatly. Variola major was the main epidemic strain by the end of the 18^th century and had caused about 400,000 deaths in Europe within a year. Survivors are often blind and disfigured. Variola minor is less toxic and has a narrower prevalence, mainly found in South Africa, South America, Europe, and Australia.

Although humans have already extinguished the spread of the virus and are no longer routinely immunized smallpox vaccines, only vaccinating experimenters at high risk, the threat still exists that it may be used by terrorists as a biological weapon for its easy transmissibility and high mortality.

Immune Responses Induced by Variola Virus Infection

After infecting the target host, variola virus would trigger both cellular and humoral immune responses. And neutralizing antibodies are able to be detected in the first week of the advent of the symptom and are capable to last for years or even decades, while complement-fixation antibodies are usually detected in the second to third weeks, and usually decline within a year. Cellular immune response is the key to controlling the development of the disease. Virus-specific cytotoxic T cells can be detected four days after infection, which can lead the infected cells to lyse and therefore prevent the virus from spreading. An in-depth understanding of the immune effects elicited by the virus infecting the body is the basis for designing a vaccine against the virus. At present, the understanding of the immune mechanism of variola virus has been comprehensive. It is a strategy of vaccine design to speculate the protective antigen of vaccine based on the immune response caused by authentic virus infection in the body, and it is also one of the indicators for evaluating the effectiveness of vaccine candidates.

Fig. 2 Immune response pathways activated by variola virus (Kennedy RB and Ovsyannikova IG, 2009)

Antigenic Structure

Viruses of the Orthopoxviruses genus have a large number of antigenic sites associated with immune protection and polypeptides that define specific cellular receptors. There are many highly cross-reactive antigens and their specific antigens between different viruses of the genus. Cross-protection between vaccinia virus and variola virus is the result of a serological cross-reactivity relationship between these viruses. Related studies of vaccinia virus have shown the importance of protective antigens in vaccine effectiveness. Combined immunization with VACV L1R (IMV immunogen) and A33R (EEV immunogen) protects mice from lethal dose challenge with poxvirus, producing a protective effect that is significantly stronger than that of either antigen alone (Hooper JW and Custer DM, 2003). These data indicate that IMV and the combined use of EEV are necessary to achieve complete immune protection. Determining the protective antigen of a virus is the basis and the most critical part of vaccine design. Creative Biolabs has a variety of strategies and techniques for the prediction and screening of protective antigens, which can greatly improve the efficiency and effectiveness of your vaccine design.

Table1. Several epitopes that targeted B and T cells from vaccinia virus

The Development of the Smallpox Vaccine

As a highly virulent pathogen that seriously affects human health and quality of life, and because of its potential to be used as a biological weapon by extremists, the research of smallpox vaccine has always been a hot spot for scientists. Historically, vaccines preventing smallpox are prepared from the less pathogenic vaccinia virus strains. Most commonly used are NYCBH (New York City Board of Health) strain and CVI-78 as well as CVII strains attenuated from the NYCBH. In China and UK, the Temple of Heaven (Tian Tan) strain originated from variola virus and Lister strain are generally vaccinated public respectively. Currently, these vaccines plus the newly accepted MVA derived from the modified Ankara strain and the solely licensed vaccine Dryvax by FDA as well as the frozen APSV preparation are still being used to protect researchers at high risk handling variola virus and other related viruses. Besides the already used vaccines mentioned above, there are some alternative vaccines candidates in the pipeline. Among which, the LC16m8, a derivative from the Lister strain, shows a good safety profile and efficacy in more than 100,000 inoculated children. The result of phase I clinical trial in which CCSV (Cell-cultured smallpox vaccine) and Dryvax were both evaluated in terms of safety and immunogenicity showed that CCSV could induce comparable humoral and cellular immune responses to that of Dryvax. Furthermore, CCSV is still immunogenic at doses less than 50 times the recommended dose of Dryvax. In addition, replication-defective vaccines such as modified vaccinia Ankara (MVA), NYVAC developed from the Cophehagen strain, dVV-L derived from the Lister strain and DNA vaccines as well as subunit vaccines made from outer membranes of the vaccinia virus are all being assessed.

Creative Biolabs relies on decades of experience in vaccine development and advanced technologies and platforms to deliver industry-leading strengths in the development of smallpox vaccines. We specialize in the research of various types of smallpox vaccines and can provide you with all-round as well as high-quality services from all stages including virus strain improvement, vaccine design, candidate construction, immunogenicity evaluation and optimization to clinical trials.

References

1. Kennedy RB, (2009). “The immunology of smallpox vaccines” Curr Opin Immunol. 21(3):314-20
2. Hooper JW, (2003). “Four-gene-combination DNA vaccine protects mice against a lethal vaccinia virus challenge and elicits appropriate antibody responses in nonhuman primates” Virology. 306(1):181-95

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.