Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?

Okeke, Malachy I.; Okoli, Arinze S.; Diaz, Diana; Offor, Collins; Oludotun, Taiwo G.; Tryland, Morten; Bøhn, Thomas; Moens, Ugo

Poxviruses have a linear double stranded DNA genome of approximately 130 kbp (seal parapox virus)-360 kbp (canarypox virus) and their entire morphogenesis is within the cytoplasm of infected cells. A milestone in vaccinology was achieved when smallpox, a highly lethal disease caused by variola virus (VARV), a member of the genus Orthopoxvirus and family Poxviridae [20] was officially declared extinct. Variola major and minor viruses accounted for approximately 30% and 1% mortality [21] . Smallpox is believed to have emerged around 10,000 BC but the origin of VARV is unknown [22] . Some protection from smallpox was achieved by transferring material from scabs taken from smallpox patients to uninfected individuals. "Variolation," as it was called, resulted in a 2% case fatality rate but was nevertheless introduced in Europe in the 18th century [23] . In 1796, Edward Jenner (1749-1823) introduced the principle of vaccination, demonstrating that cowpox virus (CPXV) could be used to prevent smallpox infection and this quickly gained acceptance [21] . Initially, vaccination was performed with CPXV [24, 25] and later VACV became the vaccine strain of choice. The origin of VACV remains unknown and is shrouded in mystery and controversy [26] . Smallpox was estimated to be responsible for 300-500 million deaths world-wide in the 20th century alone [27] and the World Health Organization (WHO) launched a strategic plan to eliminate smallpox in 1967. Smallpox was announced eradicated at the 33rd WHO assembly on 8 May 1980 [21] . The successful eradication of smallpox was possible due to early recognition and diagnosis of the disease, quarantine of patients, effective vaccination and the fact that VARV infects only humans and has no animal host reservoir.