The new ACAM2000™ vaccine and other therapies to control orthopoxvirus outbreaks and bioterror attacks

Abstract

Quarantine, case tracing and population vaccination facilitated the global eradication, in 1980, of variola virus, the causative agent of smallpox. The vaccines used during the eradication period, including Dryvax^®, the smallpox vaccine used in the USA, were live vaccinia and cowpoxvirus-based vaccines, which induced long-lasting and cross-protective immunity against variola and other related poxviruses. These vaccine viruses were produced by serial propagation in domesticated animals. The drawbacks to such serially propagated live viral vaccines include the level of postvaccination local and systemic reactions and contraindications to their use in immunocompromised individuals, individuals with certain skin and cardiac diseases, and pregnant women. In the latter stages of the population-based smallpox vaccination campaign, research began with ways to improve safety and modernizing the manufacture of vaccinia vaccines; however, with the eradication of variola this work stopped. Outbreaks of monkeypoxvirus in humans and the bioterrorist threat of monkeypox and variola virus renewed the need for improved vaccinia vaccines. ACAM2000™ is one of the new generation of smallpox vaccines. It is produced in cell culture from a clonally purified master seed stock of vaccinia derived from the New York City Board of Health strain of vaccinia. The clonally purified master seed assures a more homogeneous vaccine without the inherent mutations associated with serial propagation and the cell culture limits adventitious and bacterial contamination in vaccine production. In preclinical and clinical trials, ACAM2000 demonstrated an immunogenicity and safety profile similar to that of Dryvax.

Keywords::

• ACAM2000
• Dryvax^®
• immunogenicity
• modified vaccinia Ankara
• smallpox
• vaccine

Financial & competing interests disclosure

Mark Buller has a subcontract with Chimerix. Scott Parker’s research is funded by NIH grants NOI-AI-15436 and U54-AI-057169. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.