The last naturally occurring case of smallpox was reported in 1977. In 1980, the World Health Organization declared that smallpox had been eradicated. The Dryvax vaccine was used in smallpox eradication, and the United States has stockpiled its successor, Acam2000, for use in a potential bioterror attack. Before Acam2000 was made available, an NIAID-supported clinical trial that found that Dryvax could successfully be diluted up to five times and retain its effectiveness. These findings helped expand the number of individuals Dryvax could protect until sufficient doses of Acam2000 were made for the entire U.S. population.
People with weakened immune systems or skin conditions, such as atopic dermatitis, or eczema, are at increased risk for serious side effects from Dryvax and Acam2000. NIAID is pursuing the development of new, safer smallpox vaccines that could be used to protect these groups. One candidate developed by the biotechnology company Bavarian Nordic uses a vaccine platform technology known as Modified Vaccinia Ankara – Bavarian Nordic (MVA-BN). NIAID supported early advanced development work for this important vaccine, with initial efforts largely focused on the liquid formulation. NIAID supported preclinical evaluation through Phase II clinical trials of the investigational vaccine. The trials assessed the vaccine in healthy participants, HIV-positive volunteers, and people with atopic dermatitis or a history of atopic dermatitis. These studies evaluated safety, immunogenicity, duration of protection, and route of vaccination.
Following promising clinical trials results, MVA-BN was transitioned to the Biomedical Advanced Research and Development Authority (BARDA) for advanced development. In 2013, Canada and the European Union approved the vaccine (under the trade names IMVAMUNE and IMVANEX) for use in the general population, including people with weakened immune systems or atopic dermatitis. As of August 2014, 24 million doses were delivered to the U.S. Strategic National Stockpile (SNS) for use among these groups. BARDA also supported large Phase 3 clinical trials of the vaccine. Based on promising data from these studies, the FDA approved MVA-BN (now called JYNNEOS) in September 2019.
NIAID also supported a project to develop a freeze-dried, or lyophilized, version of the vaccine. Compared to the current liquid formulation, the lyophilized version is more stable with a longer shelf life. NIAID has transitioned this project to the U.S. Department of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA) for further development.
NIAID is supporting studies to identify adjuvants that can be used to decrease the number of vaccinations needed to provide protection and explore MVA as a platform technology to provide protection against more than one disease.