smallpox vaccine

smallpox vaccine, preparation of vaccinia virus given to prevent smallpox. Vaccinia virus is a type of poxvirus that is closely related to variola major, the virus that causes smallpox, and exposure to vaccinia provides cross immunity against smallpox. The smallpox vaccine is effective in preventing infection in about 95 percent of individuals, with protection lasting about three to five years. In 1967 the World Health Organization (WHO) began a global vaccination program against smallpox, and in 1980 the disease was officially declared eradicated.

Cross immunity

Smallpox vaccine was introduced by British physician Edward Jenner, who in 1796 used material from cowpox (vaccinia) lesions to confer protection against smallpox in humans. Prior to that use, however, the principle of vaccination had been applied by Asian physicians who gave children dried crusts from the lesions of people suffering from smallpox to protect against the disease. While some developed immunity, others developed the disease. Jenner’s contribution was to use a substance similar to, but safer than, smallpox to confer immunity.

Jenner thus exploited the relatively rare situation of cross immunity, in which immunity to one virus confers protection against another viral disease. In the case of cowpox, vaccination stimulates the adaptive immune system to produce antibodies and memory B and T lymphocytes that recognize other orthopoxviruses. Because vaccinia and variola share many surface antigens, immune responses generated against vaccinia also protect against smallpox.

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Vaccination programs and eradication

During the 19th century, vaccination programs, many of them compulsory, were instituted in many countries. At first, vaccine was obtained directly from vaccinated persons, but soon it was being commercially harvested from pustules grown on the skin of inoculated calves. Later in the century it became apparent that the cowpox virus had been supplanted in vaccines by a different strain. It is still not certain whether the new virus, called vaccinia, was a mutation of cowpox virus or a completely separate strain, but it remains the virus used for vaccine production to this day.

Routine vaccination against smallpox ended after the disease was declared eradicated in 1980. A key component of the eradication campaign was ring vaccination, in which individuals infected with smallpox were quickly identified and isolated, and their close contacts, along with the contacts of those contacts, were vaccinated to create a protective “ring” of immune individuals around each case. This strategy proved especially effective because smallpox has no nonhuman reservoir, infected persons generally become contagious only after symptoms appear, and the disease can be recognized readily by its characteristic rash. Together, these features enabled public health officials to interrupt chains of transmission.

Smallpox remains the only human infectious disease to have been eradicated worldwide through vaccination and coordinated international public health efforts. Its elimination is widely regarded as one of the greatest achievements in the history of medicine and public health.

Modern vaccines and stockpiles

In 2007 the U.S. Food and Drug Administration (FDA) approved ACAM2000, the first new smallpox vaccine licensed in the United States since 1931. Produced in cell culture, ACAM2000 contains live, replication-competent vaccinia virus and can be manufactured rapidly in large quantities for use in the event of a smallpox emergency. In 2019 the FDA approved JYNNEOS (also known as modified vaccinia Ankara–Bavarian Nordic, or MVA-BN), a live, nonreplicating vaccinia-based vaccine indicated for the prevention of both smallpox and mpox (monkeypox). Because the virus in JYNNEOS cannot replicate in human cells, the vaccine has a more favorable safety profile than ACAM2000 and generally is used for individuals who cannot safely receive replication-competent vaccinia vaccines, including some people with weakened immune systems or certain skin conditions.

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Today, smallpox vaccination is recommended only for selected groups at increased risk of exposure, including certain laboratory personnel who work with orthopoxviruses, some military personnel, and individuals vaccinated as part of emergency preparedness or outbreak response efforts. Many countries maintain strategic stockpiles of smallpox vaccine in the event of an accidental or deliberate reintroduction of the virus.

Side effects

Smallpox vaccine contains live attenuated vaccinia virus, and thus most persons vaccinated with it experience mild side effects, such as fever, headache, body aches, and rash. Some individuals, especially those with weakened immune systems, are at risk of potentially severe complications, including allergic reaction, skin rash (eczema vaccinatum), brain inflammation, or progressive vaccinia (the development of a nonhealing sore at the vaccination site). Other severe reactions may include inflammation of the heart (myocarditis) or the lining of the heart (pericarditis). Smallpox vaccine also is associated with a risk of spreading the vaccinia virus, which can happen if the individual touches the site of vaccination and then touches another area of the body or another person.