Yes, there is a smallpox vaccine, and two are currently licensed in the United States: ACAM2000 and JYNNEOS. However, smallpox vaccination is no longer recommended for the general public. The vaccines are reserved for specific groups, including laboratory workers who handle the virus and, in the event of an outbreak, people directly exposed to smallpox.
Two Vaccines, Two Different Approaches
The two available smallpox vaccines work in fundamentally different ways, and the distinction matters for safety.
ACAM2000 uses a live virus that can actually replicate inside your body. After vaccination, it produces a blister-like lesion at the injection site called a “take,” which contains infectious virus. That means the vaccine virus can spread from the vaccination site to other parts of your body or even to close contacts. People who receive ACAM2000 need to carefully cover the site and avoid skin-to-skin contact with others, particularly infants, pregnant women, or anyone with a weakened immune system.
JYNNEOS, approved in September 2019, uses a modified virus that cannot replicate in human cells. It produces no lesion, carries no risk of spreading to others, and has a substantially lower risk of serious side effects. It’s also the only smallpox vaccine approved for the prevention of mpox, since the viruses share over 90% of their genetic material. Real-world data from the mpox outbreak showed the two-dose JYNNEOS series was 66% to 89% effective against mpox.
How Each Vaccine Is Given
ACAM2000 is administered unlike any other modern vaccine. Instead of a standard injection, a healthcare provider dips a two-pronged (bifurcated) needle into the vaccine vial, then rapidly pricks the skin 15 times within a tiny area on the upper arm. No alcohol is applied beforehand because it would inactivate the virus. A trace of blood should appear within 10 to 20 seconds, and the site is then loosely covered with gauze.
Over the following days, a successful vaccination produces a visible blister that eventually scabs over. During this period, the site must stay covered. People in close contact with others, especially parents of young children, are advised to wear long-sleeved shirts over the bandaged area. The gauze and any materials that touch the site are treated as biohazardous because they contain live virus.
JYNNEOS, by contrast, is a straightforward two-dose injection given under the skin, with no special site care required afterward.
Who Can Get Vaccinated Now
Outside of an outbreak, the CDC recommends smallpox vaccination only for laboratory workers who handle smallpox or closely related viruses. Military personnel have also been routinely vaccinated. Between 2015 and 2021, the U.S. government spent nearly $3.5 billion on anthrax and smallpox medical countermeasures, and the Strategic National Stockpile maintains vaccine supplies for emergency use, though exact quantities are classified.
If a smallpox outbreak were to occur, public health officials would determine who else should be vaccinated. The vaccine can also work after exposure to the virus. Data from the eradication era showed that post-exposure vaccination was most effective when given as soon as possible, particularly within three days. After that window, it was less effective but could still reduce the severity of illness and lower the risk of death.
Cardiac Risks With ACAM2000
The most significant safety concern with ACAM2000 is heart inflammation. A large surveillance study of nearly 900,000 U.S. military service members found that about 20 out of every 100,000 recipients developed inflammation of the heart muscle or its lining. The risk was notably higher in men (roughly 22 per 100,000) compared to women (about 9 per 100,000) and in people under 40. Overall cardiovascular events of any kind occurred at a rate of about 114 per 100,000 recipients.
Because of these risks, ACAM2000 is contraindicated for people with known heart disease or those with three or more cardiac risk factors, including high blood pressure, diabetes, high cholesterol, smoking, or a family history of early heart disease.
Who Should Not Receive ACAM2000
The list of contraindications for ACAM2000 is unusually long compared to most vaccines, largely because the live virus can cause severe complications in certain people. You should not receive it if you have eczema, atopic dermatitis, psoriasis, or other active skin conditions that break the skin’s barrier. The virus can spread across damaged skin and cause a dangerous condition called eczema vaccinatum.
People with weakened immune systems are also excluded. This includes those with HIV/AIDS, leukemia, lymphoma, or other cancers, organ transplant recipients, and anyone on immunosuppressive therapies. Pregnant and breastfeeding women and children under one year old should not be vaccinated. Because the vaccine site sheds live virus, household contacts of the person being vaccinated are also screened for these same conditions.
JYNNEOS was developed in large part to provide an option for these higher-risk groups. Since it cannot replicate, it does not cause the skin lesion, cannot spread to contacts, and carries none of the same contraindications related to skin conditions or immune suppression.
How Long Protection Lasts
Smallpox vaccination appears to produce remarkably durable immunity. A population-based study in Taiwan found that over 80% of people vaccinated before 1979 still had detectable antibodies against the vaccine virus, with 84% of those showing active neutralizing ability. Some of the oldest participants had been vaccinated more than 70 years earlier, and most still had antibody levels above the threshold considered protective.
Antibody levels did decline with age, and cross-protection against mpox was notably weaker. Even after a JYNNEOS booster, people without prior smallpox vaccination had low levels of mpox-neutralizing antibodies. This suggests that while a single historical vaccination provides long-lasting protection against smallpox itself, mpox may require its own targeted vaccination strategy.