Infectious Diseases

Does the Smallpox Vaccine Provide Protection Against Monkeypox?

Andia Tofighbenam—McMaster Honours Life Sciences 2024

Despite the name, chickens do not give humans chickenpox. Wouldn’t it be nice if the same could be said about monkeypox?

Human monkeypox is a viral zoonotic disease (spread between humans and animals), first discovered in laboratory monkeys in 1958, at the State Serum Institute in Denmark (1). The monkeypox virus (MPXV) is a member of the orthopoxviral genus from the Poxviridae family and is spread by contact with body fluids, lesions, and respiratory droplets of an infected person or animal (2). This enveloped double-stranded DNA virus has two strains: the west African clade and the central African clade (Congo Basin). As opposed to the west African clade, the central African clade is more transmissible and severe (2). The incubation period of this virus can range from 5 to 21 days, starting with a fever, extreme headache, lack of energy (asthenia), and muscle aches (myalgia). Around 1 to 3 days following a fever, skin eruption begins on the face, hands, feet, genitals, and cornea. These rashes evolve from macules to papules, vesicles, pustules, and crusts, which eventually fall off (2).

The first identified human monkeypox case was discovered in Africa in 1970, two years after the elimination of smallpox. Although not new, the west African clade of monkeypox has recently become a global outbreak concern (2). In 2003, the United States experienced the first monkeypox outbreak outside Africa. By May 2022, several human monkeypox cases were discovered in multiple non-endemic countries (2).

SOURCE: The Lancet

Another virus that is a member of the orthopoxvirus family is smallpox. Smallpox is an acute contagious disease caused by the variola virus and was the cause of millions of deaths before its eradication in 1980 (4).  There are two types of the variola virus: variola major and variola minor, both of which are spread by exchanging body fluids and large respiratory droplets with an infected individual. Variola major is exceedingly severe and has a mortality rate of 30%, while variola minor had a mortality rate of 1%. Symptoms of this virus include fever, back pain, fatigue, and a characteristic rash consisting of bumps filled with clear fluid that later turns into pus and dries out (4). 

SOURCE: The Lancet

Although both smallpox and monkeypox have similar symptoms, smallpox is not a zoonotic disease and is more severe. With that being stated, they are both members of the orthopoxvirus family, have 2 strains of differing severities, are more fatal in children when compared to adults, and are spread in similar ways (6).

Due to their similarities, smallpox vaccines are effective against the monkeypox virus. There are currently two smallpox vaccines effective for monkeypox as well: IMVAMUNE and ACAM2000. IMVAMUNE is an attenuated, non-replicating orthopoxvirus vaccine (7). This live viral vaccine was licensed in September 2019 by the FDA (US Food and Drug Administration) and is 85% effective against monkeypox. ACAM2000 was FDA licensed in August 2007 and is also made of live vaccinia virus. The Centers for Disease Control and Prevention set emergency access measures allowing access to this vaccine during non-variola orthopoxvirus (monkeypox) outbreaks (7).

Although there is no current treatment specific to monkeypox, an antiviral drug that protects against smallpox can also be used against monkeypox due to their similarities (8). This drug is called Tpoxx, or Tecovirimat, and is manufactured by SIGA technologies. Although this drug may be used for monkeypox treatment, it is important to note that it is only FDA-approved for the treatment of smallpox. For this reason, a consent form must be filled out before Tecovirimat is administered to patients with monkeypox (8).

With their differences kept in mind, smallpox and monkeypox are still both members of the orthopoxvirus family. This is advantageous as certain smallpox vaccines can be used for monkeypox, given there is currently no cure for the zoonotic monkeypox virus. 


1. Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis. The Lancet Infectious Diseases [Internet]. 2004 Jan [cited 2022 Nov 23];4(1):15–25. Available from:

‌2. World. Monkeypox [Internet]. World Health Organization: WHO; 2022 [cited 2022 Nov 23]. Available from:

3. Moore, Z. S., Seward, J. F., & Lane, J. M. (2006). Smallpox. The Lancet, 367(9508), 425–435.‌‌

4. World. Smallpox [Internet]. World Health Organization: WHO; 2019 [cited 2022 Nov 23]. Available from:

‌5. Geddes AM. The history of smallpox. Clinics in Dermatology [Internet]. 2006 May [cited 2022 Nov 23];24(3):152–7. Available from:

‌6. ​​Kmiec D, Kirchhoff F. Monkeypox: a new threat?. International journal of molecular sciences. 2022 Jul 17;23(14):7866. Available from:

7. Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and Treatment of Monkeypox. Drugs [Internet]. 2022 Jun [cited 2022 Nov 23];82(9):957–63. Available from:

‌8. ​​CDC. Patient’s Guide to Monkeypox Treatment with Tecovirimat (TPOXX) [Internet]. Centers for Disease Control and Prevention. 2022 [cited 2022 Nov 23]. Available from:

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