Abstract
Various vaccinia virus (VACV) strains were applied during the smallpox vaccination campaign to eradicate the variola virus worldwide. After the eradication of smallpox, VACV gained popularity as a viral vector thanks to increasing innovations in genetic engineering and vaccine technology. Some VACV strains have been extensively used to develop vaccine candidates against various diseases. Modified vaccinia virus Ankara (MVA) is a VACV vaccine strain that offers several advantages for the development of recombinant vaccine candidates. In addition to various host-restriction genes, MVA lacks several immunomodulatory genes of which some have proven to be quite efficient in skewing the immune response in an unfavorable way to control infection in the host. Studies to manipulate these genes aim to optimize the immunogenicity and safety of MVA-based viral vector vaccine candidates. Here we summarize the history and further work with VACV as a vaccine and present in detail the genetic manipulations within the MVA genome to improve its immunogenicity and safety as a viral vector vaccine.
Highlights
Introduction of HostRange-Related Genes into Modified vaccinia virus Ankara (MVA) Which Allow for Growth in Human CellsAs previously mentioned, MVA is incapable of assembling infectious virions in human cells [86,88]
While the historical HindIII fragment letter/open reading frames (ORFs) number nomenclature was based on the vaccinia virus (VACV) strain Copenhagen [39], improved sequencing techniques and bioinformatic analysis were applied in the following years that resulted in a distinct ORF-based nomenclature for other strains such as Western Reserve (WR) [40] and MVA [41]
In addition to elucidating the molecular mechanisms underlying MVA host restriction in humans, the genes mentioned before, alone or in combination, may prove highly effective in therapeutic approaches investigating the oncolytic potential of MVA or for vaccination strategies based on recombinant MVA with regained yet controllable replication potential
Summary
Orthopoxviruses are large, enveloped, double-stranded DNA (dsDNA) viruses that belong to the large family of Poxviridae. Poxviruses replicate within special organelles which are established after infection in the cytoplasm called viral factories rather than the host nucleus [2–4] which greatly reduces the possibility of viral DNA integration into the host genome preventing the interruption of host genes and carcinogenesis. They can infect a wide variety of cell types, including keratinocytes, fibroblasts, and immune cells such as antigen-presenting cells [5]. VACV, a member of the poxvirus family, has been extensively used to induce crossprotection against variola virus (VARV), thanks to highly conserved structural proteins with other orthopoxviruses (OPXV), reduced virulence, and high immunogenicity [7,8]. The most commonly used strains were New York City Board of Health (NYCBH) in North America, Academic Editor: Michael
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