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

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. Author summary: Rabies still remains a neglected zoonosis after a long history of vaccination. Considering the severity of the disease and its continued high incidence in low-income countries, the development of a next generation vaccine is warranted. We utilized a group C, replication-defective chimpanzee adenovirus vector to develop a novel vaccine against rabies. Mice vaccinated with ChAd155-RG survived after rabies infection and non-human primates injected with a single dose of this vaccine developed strong and durable neutralizing antibody responses which could be effectively boosted with a licensed vaccine, demonstrating the compatibility of the novel vectored vaccine with the current post-exposure prophylaxis in the event of rabies virus exposure. Importantly, we show that ChAd155-RG induced neutralizing antibodies can neutralize also lyssavirus species (EBLV-1 and EBLV-2) found in bat reservoirs. These studies paved the way to the clinical testing of the ChAd155-RG based rabies vaccine as a single-dose, low cost, preventative rabies vaccine candidate. [ABSTRACT FROM AUTHOR]