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. CDC provides smallpox vaccine to these recommended individuals as needed.
The Strategic National Stockpile (SNS) has three smallpox vaccines:
- ACAM2000® – the only licensed smallpox vaccine in the United States
- Aventis Pasteur Smallpox Vaccine (APSV) and Imvamune – investigational vaccines 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.
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®.
Imvamune (MVA-BN) is a replication-deficient smallpox vaccine currently under development and seeking FDA approval. Unlike ACAM2000® and APSV, Imvamune is an attenuated live virus vaccine.
As a replication-deficient vaccine, it would be recommended for persons with certain immune deficiencies or conditions. Should a smallpox emergency occur, Imvamune would be made available for use under an EUA for persons of all ages with a diagnosis of HIV or atopic dermatitis during a post-event, pre-exposure setting. The specific clinical guidance on use of Imvamune in a smallpox emergency will be based on risk of exposure and relative contraindications to ACAM2000®.
Unlike ACAM2000® and APSV, Imvamune 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.
Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses – Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015 Source: MMWR 2016, 65(10);257–262.
Smallpox Vaccination and Adverse Reactions: Guidance for Clinicians Source: MMWR 2003, 52(RR04);1-28.
Clinical Guidelines for Smallpox Vaccine Use in a Postevent Vaccination Program Source: MMWR 2015, 64(RR02);1-26.