Primary prevention of smallpox consists in the administration of the vaccinia vaccine, which attenuates or suppresses the manifestations of the disease, if administrated soon after infection has occurred. In the absence of an outbreak, the vaccine is only administered to clinical and/or laboratory workers dealing with the virus in specialized laboratories. It has several adverse effects, particularly in immunosuppressed individuals, those with heart conditions or allergies, for whom its administration must be guided by specific rules.

The administration of the vaccine can attenuate, sometimes prevent, the manifestations of smallpox. The vaccine is made from a virus called vaccinia which is a “pox”-type virus related to smallpox. The vaccine does not contain the smallpox virus and therefore cannot transmit smallpox. However, it contains the “live” vaccinia virus, not a dead virus like many others, for which the vaccination site must be cared for carefully, in order to prevent the virus from spreading.^[1] The vaccine is given in the upper arm, using a bifurcated needle, that is dipped into the vaccine solution. When removed, the needle retains a droplet of the vaccine. It is used to prick the skin a number of times in a few seconds. The pricking is not deep, reaching basilar epithelium, but it will cause a sore spot and one or two droplets of blood will be formed.^[2]

If the vaccination is successful, 1 or 2 droplets of blood will be formed within the site of the vaccine, a few seconds after administration, and a cellular reaction will then occur. This will lead to the formation of the Jennerian pustule (1-2 cm), considered to be the major reaction. The Jennerian pustule is a sign of successful vaccination, which leads to full immunity in more than 95% of cases, possibly for 5 to 10 years.

Below is the progression of the appearance of the local of administrations of the vaccine: a red and itchy bump develops at the vaccine site within 3 to 4 days. During the first week, the bump becomes a large blister, fills with pus, and begins to drain. During the second week, the blister begins to dry up and a scab is formed. The scab then falls off during the third week, leaving a small scar.^[2]

People who were vaccinated prior to 1972, if revaccinated, may experience accelerated immune response.

Three generations of vaccines have been developed so far:

• 1st generation – a mixture of related viruses, which differ from the remaining orthopoxviruses. Reactions to these generation include:^[1][4][5]

• Fever
• Regional swelling
• Edema
• Headache
• Painful lymphadenitis

• 2nd generation – individual vaccinia clones, derived from viruses which are genetically similar, to the ones that made the 1st generation vaccine. This generation had a more efficient production of the vaccine.^[5][6]

• 3rd generation – developed from the attenuated vaccinia strains, after genetic manipulation or multiple passage through non-human tissue. Contains strains not as virulent as previous generations, and therefore safer, mainly because of a delay in replication of the virus.^[5][6][7][8]

Since smallpox was declared eradicated, vaccination is not advised for common citizens. The only people with formal indication for vaccinia vaccine are the laboratory or clinical individuals who work with the virus at specialized laboratories.^[1]

The following adverse events to the vaccine have been reported:^{[5][9][10][11]}

• Fetal vaccinia
• Progressive vaccinia
• Generalized vaccinia
• Non-specific rashes
• Eczema vaccinatum
• Encephalitis
• Myopericarditis

In the absence of reintroduction of smallpox, vaccination is contraindicated in the following:^[5][12]

• Patients with allergy to vaccine components
• History of atopic dermatitis
• History of exfoliative skin disorders
• Inflammatory eye disorders
• Immunosuppressed patients
• Heart disease
• Pregnancy
• Disease cases in the family
• Children <1 year
• Breastfeeding

After vaccination it is important to follow instructions for the care of the vaccine site. Because the virus is alive, it can spread to other parts of the body, or to other people. The vaccinia virus may cause:^[2]

• Rash
• Fever
• Headache
• Body pain

Elderly and pregnant women are prone to severe complications following the vaccinia virus vaccine.

Vaccination within 3 days of exposure will prevent or significantly lessen the severity of smallpox symptoms in the vast majority of people. Vaccination 4 to 7 days after exposure likely offers some protection from the disease or may modify its severity.^[2]

The algorithm below demonstrates the action protocol in the presence of a patient who appears to show an adverse reaction to the smallpox vaccine.^[2]