Abstract
rVSVΔG-ZEBOV-GP is a live, attenuated, recombinant vesicular stomatitis virus (rVSV)-based vaccine for the prevention of Ebola virus disease caused by Zaire ebolavirus. As a replication-competent genetically modified organism, rVSVΔG-ZEBOV-GP underwent various environmental evaluations prior to approval, the most in-depth being the environmental risk assessment (ERA) required by the European Medicines Agency. This ERA, as well as the underlying methodology used to arrive at a sound conclusion about the environmental risks of rVSVΔG-ZEBOV-GP, are described in this review. Clinical data from vaccinated adults demonstrated only infrequent, low-level shedding and transient, low-level viremia, indicating a low person-to-person infection risk. Animal data suggest that it is highly unlikely that vaccinated individuals would infect animals with recombinant virus vaccine or that rVSVΔG-ZEBOV-GP would spread within animal populations. Preclinical studies in various hematophagous insect vectors showed that these species were unable to transmit rVSVΔG-ZEBOV-GP. Pathogenicity risk in humans and animals was found to be low, based on clinical and preclinical data. The overall risk for non-vaccinated individuals and the environment is thus negligible and can be minimized further through defined mitigation strategies. This ERA and the experience gained are relevant to developing other rVSV-based vaccines, including candidates under investigation for prevention of COVID-19.
Highlights
Ebola virus disease (EVD), caused by Ebola virus (EBOV; species: Zaire ebolavirus), carries an extremely high case fatality rate, ranging from 40 to 70% in several outbreaks over the last decade [1].EVD survivors frequently suffer from debilitating long-term sequelae, including musculoskeletal pain, neurocognitive deficits, depression, fatigue, ocular disorders, and immune dysfunction [2,3,4,5].Apart from isolated laboratory accidents, all outbreaks originated from rural regions of Western and Middle Africa [1]
These results suggest that if a pig were to become infected with recombinant vesicular stomatitis virus (rVSV)∆G-ZEBOV-GP, there is limited pathogenicity and the risk of further spread to additional animals is very low
The most important consideration was the likelihood of rVSV∆G-ZEBOV-GP becoming persistent and invasive through direct and/or indirect interactions between the vaccine and non-target organisms
Summary
Ebola virus disease (EVD), caused by Ebola virus (EBOV; species: Zaire ebolavirus), carries an extremely high case fatality rate, ranging from 40 to 70% in several outbreaks over the last decade [1]. ZEBOV-GP, a live, attenuated, recombinant vesicular stomatitis virus (rVSV)-based vaccine specific to EBOV [33] In this chimeric virus vaccine, the wild-type gene sequence for the VSV envelope glycoprotein (VSV-G). VSV epidemiology and ecology, including the virus’ natural host reservoir species (i.e., a vertebrate species capable of developing sufficiently high viremia to infect hematophagous vectors) and its transmission cycle, are only incompletely understood [15,68]. Experimental evidence suggests that mosquitoes and flies can vertically transmit VSV to their embryonated eggs [70] and that biting midges can transmit the virus venereally [32] Given these multiple modes of transmission, the wide range of susceptible host species, and the different types of insect vectors, the ecology of VSV is exceedingly complex. A variety of other insect species may act as additional mechanical and/or biological vectors to transmit the virus to livestock and humans [15,16,17,19,21,29,30,31,41]
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