As with the Sterne (veterinary) anthrax vaccine strain and the similar British anthrax vaccine (known as AVP), AVA lacks the capsule plasmid pXO2 (required for full virulence) and is composed chiefly of the anthrax protective antigen (PA) with small amounts of edema factor (EF) and lethal factor (LF) that may vary from lot to lot. Other uncharacterized bacterial byproducts are also present. Whether or not the EF and LF contribute to the vaccines efficacy is not known. AVA has smaller amounts of EF and LF than AVP. Adjuvant
AVA contains aluminium hydroxide (alhydrogel) to adsorb PA as well as to serve as an adjuvant (immune enhancer). As such it is believed to stimulate humoral, but not cell-mediated, immunity. Each dose of the vaccine contains no more than 0.83 mg aluminum per 0.5 mL dose. (This is near the allowed upper limit of 0.85 mg/dose.) It also contains 0.0025% benzethonium chloride as a preservative and 0.0037% formaldehyde as a stabilizer. The mechanism of action of the adjuvant is not entirely understood. Potency/immunogenicity
Vaccination of humans with AVA induces an immune response to PA. More than 1/3 of subjects develop detectable anti-PA IgG after a single inoculation; 95% do so after a 2nd injection; and 100% after 3 doses. The peak IgG response occurs after the 4th (6 month) dose. The potency of AVA vaccine lots is routinely determined both by the survival rates of parenterally challenged guinea pigs and their anti-PA antibody titres as measured by an enzyme linked immunosorbant assay (ELISA).
History
Originally researched by the National Institute of Allergy and Infectious Diseases, the drug was owned by Viropharma and discovered in collaboration with scientists at the United States Army Medical Research Institute of Infectious Diseases. It is owned and manufactured by Siga Technologies. Siga and Viropharma were issued a patent for tecovirimat in 2012. Clinical trials
As of 2009, the results of clinical trials support its use against smallpox and other related orthopoxviruses. It shows potential for a variety of uses including preventive healthcare, as a post-exposure therapeutic, as a therapeutic, and an adjunct to vaccination.Tecovirimat can be taken by mouth and as of 2008, was permitted for phase II trials by the U.S. Food and Drug Administration (FDA). In phase I trials, tecovirimat was generally well tolerated with no serious adverse events. Due to its importance for biodefense, the FDA designated tecovirimat for fast-track status, creating a path for expedited FDA review and eventual regulatory approval. On 13 July 2018, the FDA announced approval of tecovirimat for the treatment of smallpox.On 25 August 2022, the AIDS Clinical Trials Group (ACTG) began a randomized, placebo-controlled, double-blinded trial on the safety and efficacy of tecovirimat for monkeypox, known as STOMP (Study of Tecovirimat for Human Monkeypox Virus), aiming to enroll at least 500 participants with acute monkeypox infection.