This information is about preventing or responding to smallpox. For the latest information about the current mpox outbreak, including information on symptoms, prevention, and vaccines, please visit CDC’s Mpox site.

Routine vaccination against smallpox in the United States ended in the 1970s. However, for specific populations at high risk of occupational exposure to orthopoxviruses, the 2015 Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination against the disease. The Centers for Disease Control and Prevention’s (CDC) Drug Services provides smallpox vaccine to these recommended individuals as needed.

The Strategic National Stockpile (SNS) has three smallpox vaccines:

  • ACAM2000® and JYNNEOSTM (also known as Imvamune or Imvanex) are the only two licensed smallpox vaccines in the United States.
  • Aventis Pasteur Smallpox Vaccine (APSV) is an investigational vaccine that may be used in a smallpox emergency under the appropriate regulatory mechanism (i.e., Investigational New Drug application [IND] or Emergency Use Authorization [EUA]).


The U.S. Food and Drug Administration (FDA) has licensed ACAM2000®, (Smallpox [Vaccinia] Vaccine, Live), a replication-competent vaccine, for active immunization against smallpox disease in persons determined to be at high risk for smallpox infection. The vaccine does not contain variola virus and cannot cause smallpox. It contains vaccinia virus, which belongs to the poxvirus family, genus Orthopoxvirus. The vaccinia virus may cause rash, fever, and head and body aches. In certain groups of people, particularly those who are immunocompromised, complications from the vaccinia virus can be severe.

Replication-competent smallpox vaccine consists of a live, infectious vaccinia virus that can be transmitted from the vaccine recipient to unvaccinated persons who have close contact with the inoculation site, or with exudate from the site. The risk of side effects in household contacts is the same as those for the vaccine recipient. Therefore, the vaccination site requires special care to prevent the virus from spreading.

ACAM2000® is administered as a single dose by the percutaneous route using the multiple puncture technique.

The 2015 ACIP recommendations advise routine vaccination of laboratory personnel who directly handle cultures of, or animals infected with:

  • Replication-competent vaccinia virus
  • Recombinant vaccinia viruses derived from replication-competent vaccinia strains (i.e., those that are capable of causing clinical infection and producing infectious virus in humans), or
  • Other orthopoxviruses that can infect humans (e.g., monkeypox, cowpox, and variola)

Routine vaccination is not recommended for, but should be offered to:

  • Healthcare personnel (e.g., physicians, nurses) who currently treat or anticipate treating patients with vaccinia virus infections
  • Anyone administering ACAM2000®

In the event of a smallpox emergency, ACAM2000® would be made available to persons exposed to smallpox virus or who are at high risk of smallpox infection, depending on the circumstances of the event.

Aventis Pasteur Smallpox Vaccine (APSV)

APSV is another replication-competent vaccinia virus vaccine in the Strategic National Stockpile, with a safety profile anticipated to be similar to ACAM2000®. It is an investigational vaccine. In a smallpox emergency, APSV would be made available under an IND or EUA for use in circumstances where ACAM2000® is depleted, not readily available, or in a case-by-case basis where ACAM2000® is contraindicated.

APSV is also administered by the same multiple puncture technique as ACAM2000®.


The FDA has licensed JYNNEOSTM (also known by the brand names Imvamune and Imvanex), a replication-deficient smallpox vaccine, for the prevention of smallpox and monkeypox. Unlike ACAM2000® and APSV, JYNNEOSTM is an attenuated live virus vaccine.

As a replication-deficient vaccine, it can be used for vaccination of people 18 years and older with certain immune deficiencies or conditions, such as HIV or atopic dermatitis.  JYNNEOSTM has been studied in people with HIV and atopic dermatitis and no severe adverse events were identified. The specific use of JYNNEOSTM in a smallpox emergency will be based on risk of exposure and relative contraindications to ACAM2000®.

Unlike ACAM2000® and APSV, JYNNEOSTM is administered subcutaneously as two doses separated by 4 weeks (one dose at week 0 and a second dose at week 4) for primary vaccinees (individuals who have never been vaccinated against smallpox or do not recall receiving a smallpox vaccination in the past). Individuals previously vaccinated against smallpox receive one dose.