High dose of vesicular stomatitis virus-vectored Ebola vaccine causes vesicular disease in swine without horizontal transmission

Authors: MOROZOV, IGOR - Kansas State University; MONATH, THOMAS - Newlink Genetics Corporation; MEEKINS, DAVID - Kansas State University; TRUJILLO, JESSIE - Kansas State University; SUNWOO, SUN-YOUNG - Kansas State University; URBANIAK, KINGA - Kansas State University; KIM, IN JONG - Kansas State University; NARAYANAN, SANJEEV - Kansas State University; INDRAN, SABARISH - Kansas State University; MA, WENJUN - Missouri University Of Science And Technology; Wilson, William - Bill; O'CONNOR, CASSANDRA - Battelle Memorial Institute; DUBEY, SHERI - Merck Research Laboratories; TROTH, SEAN - Merck Research Laboratories; COLLER, BETH-ANN - Merck Research Laboratories; NICHOLS, RICHARD - Newlink Genetics Corporation; RICHT, JUERGEN - Kansas State University

Submitted to: Emerging Microbes & Infections
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/21/2021
Publication Date: 4/2/2021
Citation: Morozov, I., Monath, T.P., Meekins, D.A., Trujillo, J.D., Sunwoo, S., Urbaniak, K., Kim, I., Narayanan, S.K., Indran, S.V., Ma, W., Wilson, W.C., O'Connor, C., Dubey, S., Troth, S.P., Coller, B., Nichols, R., Richt, J. 2021. High dose of vesicular stomatitis virus-vectored Ebola vaccine causes vesicular disease in swine without horizontal transmission. Emerging Microbes & Infections. 10(1):651-663. https://doi.org/10.1080/22221751.2021.1903343.
DOI: https://doi.org/10.1080/22221751.2021.1903343

Interpretive Summary: Outbreaks of Ebola virus disease (EVD) in Africa in recent years have clearly demonstrates the need for a safe and efficacious vaccine. ERVEBO®, a recombinant vaccine, designed to control outbreaks and mitigate its threat to global health was approved by the FDA and EMA in late 2019 for use in prevention of EVD. Since the parental virus, which was used to construct ERVEBO®, is pathogenic for livestock and the vaccine virus may be shed at low levels by vaccinated humans, widespread deployment of the vaccine required investigation into its infectivity and transmissibility to susceptible livestock species. This study demonstrated that high doses of the vaccine did induce clinical symptoms in swine, with a proportion of pigs developing ulcerative vesicular lesions at the nasal injection site and in the feet. Uninoculated contact control pigs that were co-mingled with vaccine inoculated pigs did not become infected or display any clinical signs of disease, indicating that the vaccine is not readily transmissible to naïve pigs during prolonged close contact. In contrast, virulent strain of the virus had a shorter incubation period and was transmitted to contact control pigs. These results indicate that the recombinant vaccine causes vesicular illness in swine when administered at a high dose. Moreover, the study demonstrates the recombinant vaccine is not readily transmitted to uninfected pigs, encouraging its safe use as an effective human vaccine.

Technical Abstract: The recent impact of Ebola virus disease (EVD) on public health in Africa clearly demonstrates the need for a safe and efficacious vaccine to control outbreaks and mitigate its threat to global health. ERVEBO® is an effective recombinant Vesicular Stomatitis Virus (VSV)-vectored Ebola vaccine (rVSV'G-ZEBOV- GP) that was approved by the FDA and EMA in late 2019 for use in prevention of EVD. Since the parental virus VSV, which was used to construct ERVEBO®, is pathogenic for livestock and the vaccine virus may be shed at low levels by vaccinated humans, widespread deployment of the vaccine required investigation into its infectivity and transmissibility in VSV-susceptible livestock species. We therefore performed a comprehensive clinical analysis of the ERVEBO® vaccine virus in swine to determine its infectivity and potential for transmission. A high dose of the rVSV'G-ZEBOV-GP vaccine resulted in VSV-like clinical signs in swine, with a proportion of pigs developing ulcerative vesicular lesions at the nasal injection site and feet. Uninoculated contact control pigs co-mingled with rVSV'G-ZEBOV-GP-inoculated pigs did not become infected or display any clinical signs of disease, indicating the vaccine is not readily transmissible to naïve pigs during prolonged close contact. In contrast, virulent wild-type VSV Indiana had a shorter incubation period and was transmitted to contact control pigs. These results indicate that the rVSV'G-ZEBOV-GP vaccine causes vesicular illness in swine when administered at a high dose. Moreover, the study demonstrates the ERVEBO® vaccine is not readily transmitted to uninfected pigs, encouraging its safe use as an effective human vaccine.