The purpose of the research overseen by the WHO Advisory Committee on Variola Virus Research (Advisory Committee), as mandated by the World Health Assembly, (1) is to develop medical countermeasures to enhance global preparedness in the event of natural, accidental or deliberate re-emergence of smallpox. Continuing retention of variola virus stocks by the repositories has been authorized by the World Health Assembly for this purpose insofar as the research and countermeasures developed are of public health benefit for humanity.
The Advisory Committee held its 22nd meeting on 4-5 November 2020 by video conference, hosted by the WHO Smallpox Secretariat in Geneva, Switzerland. The full report of the meeting is available on the WHO website. (2)
Variola virus repositories
The Advisory Committee received reports on the variola virus collections held by the 2 authorized repositories: the Federal Budgetary Research Institution, State Research Centre of Virology and Biotechnology (VECTOR), Federal Service for Surveillance on Consumer Rights Protection and Human Well-being, Koltsovo, Novosibirsk Oblast, Russian Federation, and the Centers for Disease Control and Prevention (CDC), Atlanta (GA), United States of America.
The Committee received reports on the progress of approved research with variola virus. Although the COVID-19 pandemic has somewhat delayed research during the year, the Committee reviewed and recommended approval of four new proposals, 2 each from CDC and VECTOR, and continuation of previously approved projects. The outcomes of research to date are summarized below.
After approval of tecovirimat as a specific antiviral agent for smallpox in 2018, studies were conducted to meet regulatory authority post-marketing requirements. A paediatric formulation and an intravenous formulation are also being developed. It is planned to assess use of tecovirimat in conjunction with vaccination with the approved modified vaccinia Ankara smallpox vaccine (MVA) in human volunteers to determine the immunogenicity of the vaccine in the presence of the antiviral agent. The safety of brincidofovir has been evaluated in clinical trials, and it has been found to show mild, reversible side-effects; this product was approved in July 2021. A study of analogues of ST-357, another possible second-line drug, have begun. VECTOR anticipates that phase-2 and -3 trials of NIOCH-14 will begin in 2021. VECTOR also proposed testing of 15 new chemical compounds against variola virus in vitro. Both VECTOR and CDC continue to explore use of individual or mixtures of monoclonal antibodies. The humanized mouse model being developed at CDC has shown sensitivity to variola infection, with a disease profile similar to human infection.
Studies of the MVA vaccine developed by Bavarian Nordic (MVA-BN) approved in several jurisdictions for the prevention of smallpox continue in various contexts, including for the prevention of human monkeypox in the Democratic Republic of the Congo. The vaccine had an excellent safety profile and a strong memory response in health workers 2 years after initial vaccination. In 2020, Health Canada extended indications for use of the vaccine to prevention of monkeypox and other orthopoxviruses for people at risk, making the MVA vaccine the first to...