Low-dose VSV-EBOV vaccination provides rapid protection from lethal Ebola virus challenge

In the decade since the West African Ebola virus (EBOV) epidemic, several medical countermeasures against this often-fatal hemorrhagic disease have been approved by regulatory authorities for human use. This includes monoclonal antibody-based therapies and vaccines which have been stockpiled in limited quantities. One of the vaccines is based on vesicular stomatitis virus (VSV) expressing the EBOV glycoprotein (GP) as the immunogen. The vaccine is stockpiled in limited quantity for emergency use. A single high dose has been shown to rapidly protect humans within 10 days. We developed an updated version of this vaccine expressing the GP from the 2015 EBOV-Makona isolate. Here, we wanted to determine the protective efficacy within 10 days of a single moderate dose (10-fold and 1,000-fold dilution) of the updated vaccine in nonhuman primates (NHPs). As a comparator we included a 1000-fold dilution dose group of the approved vaccine expressing the EBOV-Kikwit GP. While we achieved uniform protection with the approved vaccine at the moderate dose, only 50% of the NHPs receiving the same dose of the updated vaccine expressing the EBOV-Makona GP were protected. This study highlights the importance of evaluating VSV-based vaccine stocks expressing different filovirus GPs in preclinical models prior to progression with clinical development. Our study also highlights that rapid vaccination with reduced doses still leads to protection but at the cost of "sterile" immunity raising concerns regarding EBOV persistence and potential downstream transmission. Therefore, lower vaccine doses should only be considered in cases of severe vaccine shortage.