Vaccinia Virus vs. Variola Virus

What's the Difference?

Vaccinia virus and Variola virus are both members of the Poxviridae family and share some similarities, but they also have distinct characteristics. Vaccinia virus is a non-pathogenic virus used in the smallpox vaccine, while Variola virus is the causative agent of smallpox, a highly contagious and deadly disease. Vaccinia virus is larger in size and has a broader host range compared to Variola virus, which primarily infects humans. Additionally, Vaccinia virus has a faster replication cycle and produces larger plaques in cell culture compared to Variola virus. Despite these differences, both viruses have been extensively studied due to their historical significance and potential as bioweapons.


AttributeVaccinia VirusVariola Virus
HostsHumans, animalsHumans
DiseaseUsed as a vaccine against smallpoxCauses smallpox
TransmissionPerson-to-person, animal-to-personPerson-to-person
Incubation Period10-14 days7-17 days
SymptomsMild rash, feverFever, rash, pustules
Mortality RateVery low30% (varies)
EradiationEradicated (no longer exists in the wild)Eradicated (last known case in 1977)

Further Detail


Vaccinia virus and Variola virus are both members of the poxvirus family and have significant historical importance. While Vaccinia virus has been used as a vaccine to eradicate smallpox, Variola virus is the causative agent of smallpox, a highly contagious and deadly disease. In this article, we will compare the attributes of these two viruses, highlighting their genetic makeup, clinical manifestations, transmission, and vaccination strategies.

Genetic Makeup

Vaccinia virus and Variola virus share similarities in their genetic makeup, as they both belong to the poxvirus family. However, there are notable differences between the two. Vaccinia virus has a large double-stranded DNA genome, approximately 190 kilobase pairs in length, encoding for numerous proteins involved in viral replication, immune evasion, and host interaction. In contrast, Variola virus has a smaller genome, around 186 kilobase pairs, but still contains a significant number of genes responsible for its pathogenicity.

Furthermore, Vaccinia virus has undergone extensive genetic modifications during its use as a vaccine, leading to the loss of certain genes associated with virulence. Variola virus, on the other hand, has a more stable genome and retains its pathogenicity, making it a highly dangerous virus.

Clinical Manifestations

The clinical manifestations of Vaccinia virus and Variola virus infections differ significantly. Vaccinia virus infections in humans are generally mild and self-limiting, often resulting in a localized skin lesion at the site of inoculation. These lesions typically progress through stages of papule, vesicle, pustule, and finally scab formation. In some cases, individuals may experience mild systemic symptoms such as fever, headache, and muscle aches.

In contrast, Variola virus infections cause smallpox, a severe and often fatal disease. Smallpox is characterized by a sudden onset of high fever, malaise, headache, and severe back pain. Within a few days, a rash develops, starting on the face and then spreading to the extremities. The rash progresses through different stages, including macules, papules, vesicles, pustules, and finally scabs. Smallpox is notorious for its high mortality rate, with the case fatality rate ranging from 30% to 40% in unvaccinated individuals.


Vaccinia virus and Variola virus have distinct modes of transmission. Vaccinia virus is primarily transmitted through direct contact with the vaccine site or through contact with objects contaminated with the virus, such as clothing or bandages. It is important to note that person-to-person transmission of Vaccinia virus is rare, especially in the absence of a vaccine site.

Variola virus, on the other hand, is highly contagious and can be transmitted through respiratory droplets expelled by infected individuals. Close contact with an infected person, or contact with contaminated objects such as bedding or clothing, can also lead to transmission. The ability of Variola virus to spread easily among individuals contributed to the rapid global spread of smallpox before the introduction of vaccination programs.

Vaccination Strategies

Vaccination strategies for Vaccinia virus and Variola virus differ significantly due to their distinct roles in public health. Vaccinia virus has been used as the basis for the smallpox vaccine, which played a crucial role in eradicating smallpox worldwide. The smallpox vaccine, known as vaccinia vaccine, is a live attenuated virus derived from Vaccinia virus. It provides immunity against Variola virus by stimulating the immune system to produce a protective response.

On the other hand, there is no specific vaccine available for Variola virus. The smallpox vaccine, which contains Vaccinia virus, provides cross-protection against Variola virus. However, due to the eradication of smallpox and the absence of natural Variola virus transmission, routine smallpox vaccination is no longer recommended. In certain situations, such as bioterrorism threats, a limited number of individuals may receive the smallpox vaccine as a precautionary measure.


In conclusion, Vaccinia virus and Variola virus, despite their genetic similarities, have distinct attributes and roles in public health. Vaccinia virus, used as the smallpox vaccine, has contributed to the eradication of smallpox and is associated with mild, self-limiting infections. In contrast, Variola virus causes smallpox, a severe and often fatal disease with a high mortality rate. Understanding the differences between these two viruses is crucial for appreciating the impact of vaccination programs and the importance of continued surveillance to prevent the re-emergence of smallpox.

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