From the Guidelines

Vaccinia virus is a double-stranded DNA virus belonging to the Orthopoxvirus genus [ 1 ].

It has a broad host range under experimental conditions but is rarely isolated from animals outside the laboratory [ 1 ].
Multiple strains of vaccinia virus exist, with different levels of virulence for humans and animals [ 1 ].
Examples of strains include the Temple of Heaven and Copenhagen vaccinia strains, which are highly pathogenic among animals, whereas the NYCBOH strain has relatively low pathogenicity [ 1 ].

The vaccinia virus is utilized as a live vaccine in the form of smallpox vaccine, typically administered via scarification or intradermal injection.
The vaccine is administered using the multiple-puncture technique with a bifurcated needle [ 1 ].
The virus replicates in the dermis of the skin, leading to the formation of a papule, which becomes vesicular, then pustular, and eventually forms a scab that separates 14-21 days after vaccination [ 1 ].

From the Research

Vaccinia virus (VACV) is an enveloped double-stranded DNA virus and the active ingredient of the smallpox vaccine 2.
It is a member of the Poxviridae family of large double-stranded DNA viruses 3.
VACV is the prototype of the Orthopoxvirus genus, which includes several pathogenic poxviruses of humans, such as monkeypox virus and variola virus 4.

The vaccinia virus genome encodes most if not all of the viral replication machinery, including the DNA polymerase and its processivity factor 5.
The virus replicates exclusively in the cytoplasm of infected cells, which is unusual among DNA viruses 6.
The single-stranded DNA binding protein (SSB) I3 is essential for viral replication, and its deletion results in a severe defect in DNA replication and late protein accumulation 6.

The host range of wild-type VACV is very broad among mammalian cells, and the C7L gene is essential for host range function 3.
The efficacy of the smallpox vaccine is attributed to a robust production of protective antibodies against several envelope proteins of VACV, which cross-protect against infection with pathogenic variola virus 2.
Understanding the precise interaction between the antibodies and their epitopes is helpful in the design of better vaccines against other diseases 2.