A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C

Napolitano, Federico; Merone, Rossella; Abbate, Adele; Ammendola, Virginia; Horncastle, Emma; Lanzaro, Francesca; Esposito, Marialuisa; Contino, Alessandra Maria; Sbrocchi, Roberta; Sommella, Andrea; Duncan, Joshua D.; Hinds, Jospeh; Urbanowicz, Richard A.; Lahm, Armin; Colloca, Stefano; Folgori, Antonella; Ball, Jonathan K.; Nicosia, Alfredo; Wizel, Benjamin; Capone, Stefania; Vitelli, Alessandra

Abstract

Rabies, caused by RNA viruses in the Genus Lyssavirus, is the most fatal of all infectious diseases. This neglected zoonosis remains a major public health problem in developing countries, causing the death of an estimated 25,000-159,000 people each year, with more than half of them in children. The high incidence of human rabies in spite of effective vaccines is mainly linked to the lack of compliance with the complicated administration schedule, inadequacies of the community public health system for local administration by the parenteral route and the overall costs of the vaccine. The goal of our work was the development of a simple, affordable and effective vaccine strategy to prevent human rabies virus infection. This next generation vaccine is based on a replication-defective chimpanzee adenovirus vector belonging to group C, ChAd155-RG, which encodes the rabies glycoprotein (G). We demonstrate here that a single dose of this vaccine induces protective efficacy in a murine model of rabies challenge and elicits strong and durable neutralizing antibody responses in vaccinated non-human primates. Importantly, we demonstrate that one dose of a commercial rabies vaccine effectively boosts the neutralizing antibody responses induced by ChAd155-RG in vaccinated monkeys, showing the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Finally, we demonstrate that antibodies induced by ChAd155-RG can also neutralize European bat lyssaviruses 1 and 2 (EBLV-1 and EBLV-2) found in bat reservoirs.

Citation

Napolitano, F., Merone, R., Abbate, A., Ammendola, V., Horncastle, E., Lanzaro, F., …Vitelli, A. (2020). A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C. PLoS Neglected Tropical Diseases, 14(7), Article e0008459. https://doi.org/10.1371/journal.pntd.0008459

• Journal Article Type: Article
• Acceptance Date: Jun 5, 2020
• Online Publication Date: Jul 15, 2020
• Publication Date: Jul 1, 2020
• Deposit Date: Jul 17, 2020
• Publicly Available Date: Jul 20, 2020
• Journal: PLoS neglected tropical diseases
• Electronic ISSN: 1935-2735
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 7
• Article Number: e0008459
• DOI: https://doi.org/10.1371/journal.pntd.0008459
• Keywords: Public Health, Environmental and Occupational Health; Infectious Diseases
• Public URL: https://nottingham-repository.worktribe.com/output/4772568
• Publisher URL: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008459