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Smallpox vaccination

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful.

See also the separate article Smallpox.

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Introduction and history of the smallpox vaccine1

Edward Jenner (1749-1823) published work in 1798 entitled "An enquiry into the causes and effects of the variolae vaccinae". This work was done following earlier observations that dairymaids and cowmen did not catch smallpox although they did catch cowpox. Benjamin Jesty (1737-1816) protected his family in a similar way before Jenner reported the first scientific attempt at immunisation from a hut near his home in Berkeley, Gloucestershire. Jenner scratched material from a cowpox pustule into the arm of a young local boy, James Phipps, who subsequently developed a pustule and a fever. He remained healthy when subsequently Jenner inoculated him with smallpox. "Vaccinae" means "of the cow" and "vaccination" means "protection from smallpox". At this time there were 23,000 deaths per year from smallpox in England and many more across Europe. The case fatality rate was between 20% and 60%.

In 1853 compulsory smallpox vaccination was introduced and by the 1930s smallpox had ceased to be endemic in the UK. In December 1979 the Global Commission for the Certification of Smallpox Eradication declared the world free of smallpox and in 1980 this was ratified by the World Health Assembly.2 There is now no indication for routine smallpox vaccination and now it is only used for those at particular risk or as part of an outbreak response.

Smallpox infection

Smallpox is caused by the variola virus, a DNA virus, with humans being the only known reservoir for the disease. It is spread by person-to-person contact, with an incubation period of 10 to 14 days.2 The overall mortality is about 30%.


Monkeypox virus is related to the smallpox virus and is found in rural areas of Nigeria, Congo, Sierra Leone, Cameroon and the central African republic. Most people have a mild, self-limiting illness and recover completely within three weeks without active treatment. However, there is the possibility of severe infection and (rarely) death when infection occurs in children, pregnant women or immunocompromised individuals.

There have been three outbreaks related to monkeypox in the UK between 2018 and 2022 and these have been linked to travel from Nigeria.4 Smallpox vaccination can be used to prevent the disease in those at risk, because of the similarities between smallpox and monkeypox. It is thought to be 85% effective in preventing infection.3

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Types of smallpox vaccines2

The most widely used virus used for smallpox inoculation is Vaccinia (derived from the genus Orthopoxvirus). This is a double-stranded DNA virus sharing antigenicity with the Variola virus. First- and second-generation vaccines (no longer available in the UK) were usually prepared from calf lymph, but newer third-generation vaccines (Imvanex® in Europe and the UK, Jynneos® in the USA and Imvamune® in Canada) are grown in chicken embryos. These vaccines contain a replication defective virus which has low neuropathogenicity in humans while providing good immune cover.

Current smallpox vaccines give protection for five years (partial immunity for 10 years or more) with 95% conversion rate after primary vaccination. There is currently a lack of evidence for the vaccines to modify or prevent illness post-exposure. But based on immunological responses alone, some protection may be presumed if given within a few days of exposure - ideally within four days but can be offered up to 14 days later.

Two doses are given subcutaneously (SC) or intramuscularly (IM), at least 28 days apart. Booster doses for individuals who continue to be at risk are given after no less than two years. If supply is constrained, a 0.1 ml intradermal dose can be used, in place of the 0.5 ml SC or IM dose.

Adverse effects of the smallpox vaccine2

Third-generation smallpox vaccine has a favourable adverse-event profile compared to older vaccines. The common events include local site reactions and influenza-like symptoms which are generally mild and resolve spontaneously within seven days.

Anecdotally there seems to be a greater number of adverse events when the individual has previously received a live (first- or second-generation) smallpox vaccine. Unlike the older vaccines, there have been no reports as yet of myocarditis, pericarditis or encephalitis with the third-generation vaccines.

Risk factors

Minor illnesses without fever or systemic upset should not postpone vaccination.

As the vaccine contains non-replicating virus, there is no theoretical reason for concern in pregnancy, or when it is used for immunocompromised individuals. Currently the data to substantiate that are lacking.

People who have atopic dermatitis may be more prone to develop post-injection site reactions.

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There is no indication for routine smallpox vaccination. Vaccination is recommended for:

  • Workers in laboratories where pox viruses are handled and others whose work involves an identifiable risk of exposure to pox virus.

  • Workers in healthcare environments who may be exposed to individuals with monkeypox virus.3

  • People who might be at greater risk of exposure to monkeypox because of their lifestyle choices.5

Laboratory workers should be informed of the need for the smallpox vaccine when appropriate. They may have fears about adverse effects which need to be addressed. Concerns have been expressed about smallpox in relation to bioterrorism and the availability of vaccine when half of the world's population is unvaccinated. Vaccines for the protection of troops need to be maintained.

Further information and advice

  • For further advice and guidance for laboratory staff, see Advisory Committee on Dangerous Pathogens and Advisory Committee on Genetic Modification 1990. HMSO ISBN 011885450.

  • Urgent out-of-hours support (including advice on the need for vaccination and contra-indications from the UK Health Security Agency); Tel: (+44) 020 8200 4400.

  • Advice on clinical diagnosis and treatment can be obtained from Regional Infectious Disease Units, and also from Royal Free Hospital Infection Services, 10th Floor, Royal Free Hospital, Hampstead, London, NW3 2QG; Tel: (+44) 0207 830 2606 Out-of-hours contact details are held by the 24-hour CDSC on-call duty doctor; Tel: (+44) 020 8200 6868.

  • Advice on public health is held by the 24-hour CDSC on-call duty doctor; Tel: (+44) 020 8200 6868.

Vaccine availability

Enquiries relating to the smallpox vaccine can be directed to:

  • UK Health Security Agency - (+44) 020 8200 4400.

Further reading and references

  1. Riedel S; Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent). 2005 Jan;18(1):21-5.
  2. Smallpox and Monkeypox; The Green Book Chapter 29, GOV.UK, Sept 2022
  3. Monkeypox; GOV.UK (May 2022)
  4. Monkeypox - United Kingdom of Great Britain and Northern Ireland; World Health Organization, May 2022
  5. Monkeypox; Centers for Disease Control and Prevention, May 2022

Article history

The information on this page is written and peer reviewed by qualified clinicians.

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