Vaccinia virus belongs to the family Poxvirudae and the genus Orthopoxvirus. It is a large and structurally complex DNA virus with a volume of approximately 360 × 270 × 250 nanometers. It has a brick shaped or oval shape and is composed of DNA, protein shell, and lipids. Its genome contains early and late mRNA, which guides the synthesis of replicases and structural proteins, and completes replication and assembly in the cytoplasm of host cells. It has strong stability in low temperature environments. The virus has a wide host range and is highly susceptible to humans and mice, and can be transmitted through skin wound contact. After human vaccination, it usually only causes local skin lesions, but immunocompromised individuals may develop systemic acne or encephalitis. As an antigen for smallpox vaccine, the smallpox virus is derived from artificially attenuated strains of smallpox virus, with a history of over 100 million doses administered.
Figure 1. Vaccinia virus.
Origin
Vaccinia Virus is closely related to the cowpox virus that causes cowpox. From a historical perspective, these two are often considered the same. Due to the lack of record keeping, the exact source of the acne virus is unknown, as the virus has undergone decades of repeated cultivation and transmission in research laboratories. The most common concept is the smallpox virus, both of which originate from the common ancestor virus. Some people speculate that cowpox virus was initially isolated from horses, and analysis of DNA from early (1902) smallpox vaccine samples showed a 99.7% ratio to cowpox virus.
Figure 2. Monkeypox virus.
Characteristics Of Vaccinia Virus As An Oncolytic Virus
Characteristics
Detail
Rapid Replication
Vaccinia virus can rapidly replicate within cells and lyse cells within 48-72 hours after infection.
Targeting
Compared to normal cells, the acne virus is more likely to infect actively dividing cancer cells, thus having a natural targeting ability towards cancer cells.
Safety
The DNA of the smallpox virus does not integrate into the host genome, so it does not induce tumors.
Genome Capacity
Vaccinia virus has a large genome that can accommodate at least 25 kb of exogenous genes, allowing researchers to insert genes that enhance immune response or have other therapeutic functions.
Transmission Ability
The extracellular envelope virus (EEV) produced by the smallpox virus can resist complement action, spread over long distances and cross the blood flow barrier, effectively delivering to metastatic tumors.
Immune Regulation
After infection with acne virus, it can release various cellular danger signals (DAMPs) and pathogen associated molecular patterns (PAMPs), as well as antigens related to the virus and tumor, to stimulate immune response.
Potential for Modification
Through genetic engineering modification, the tumor specificity, safety, immunogenicity, oncolytic ability, and drug efficacy of the acne virus can be further enhanced.
Clinical Application
Various modified acne viruses have entered the clinical trial stage for the treatment of different types of tumors.
Replication Process of Vaccinia Virus
VV initiates invasion through specific binding of envelope proteins to host cell surface receptors, with core targets including:
Integrin family: mainly recognizes the α V β 3, α V β 5, and α 5 β 1 integrins on the surface of host cells, and mediates viral endocytosis or membrane fusion by binding to the extracellular domain of integrins through viral envelope proteins A36R and L1R.
Epidermal growth factor receptor (EGFR): The viral protein VEGFR mimics host EGF and binds to EGFR to activate the downstream PI3K Akt pathway, providing signal support for virus invasion.
Heparin sulfate (HSPG): The viral envelope proteins A27L and D8L first bind to the cell surface HSPG with low affinity, assisting in subsequent high specificity receptor recognition and enhancing invasion efficiency.
The connection between viral proteins and host glycosaminoglycans (GAGs) mediates the internalization of the virus into host cells. In addition, viruses can also invade cells by simulating apoptosis.
Vaccine Application
Vaccinia virus infection usually occurs very mildly, although it may cause rash and fever, it usually does not cause symptoms in healthy individuals. The immune response caused by smallpox virus infection can protect people from the deadly smallpox infection. For this reason, cowpox virus has been used as a live virus vaccine against smallpox in the past. Unlike vaccines administered using weakened forms, the smallpox virus vaccine does not cause smallpox infection because it does not contain smallpox virus. However, occasional complications or vaccine adverse reactions may occur. People with weakened immune function will greatly increase the occurrence of this condition. About one in every million people will have a fatal reaction to vaccines. Currently, vaccines are only administered to healthcare workers or researchers at high risk of contracting smallpox virus, as well as military personnel in the United States. Due to the threat of smallpox virus bioterrorism, it may be necessary to widely vaccinate against this vaccine again in the future. Therefore, scientists are currently developing a new vaccine strategy for smallpox, which is safer and faster to deploy in bioterrorism events.
Preventive Treatment
The volume of vaccinia virus particles is approximately 300 × 230 × 100 nanometers, with an elliptical brick shape and containing DNA with a molecular weight of 160-170 × 10 ^ 6. There are enzymes such as RNA polymerase and nucleotide phosphohydrolase in the particles, which are stable at low temperatures. The cowpox vaccine virus can cause the agglutination of red blood cells in chickens. In various primary cultured cells such as chicken embryos, HeLa cell lines proliferate in the cytoplasm and form pocks in the serosa of developing chicken embryos. When a person is vaccinated, local lesions usually appear on the skin. But when the immune system is defective, it can invade the whole body (systemic acne, vaccine generalisata, also known as progressive post vaccination eczema), often leading to death. Less common cases include post vaccination encephalitis. This virus has been found to have interference with other viruses, as well as reorganization and reactivation within the same virus group, and has been carefully studied in conjunction with the initial infection process of this virus.
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Figure 1. Vaccinia virus.
Figure 2. Monkeypox virus.