A U.S. Government-Coordinated Effort to Leverage Non-Human Primate Data to Facilitate Ebolavirus Vaccine Development

Abstract

A United States Government (USG) interagency group, the Filovirus Animal Non-Clinical Group (FANG), has been established to support the development of biodefense medical countermeasures (MCMs). As both vaccines and therapeutics are licensed using “non-traditional pathways”, such as the U.S. Food and Drug Administration’s (FDA) Animal Rule (AR), non-human primate (NHP) models and associated assays have been developed and standardized across BSL4 testing sites to evaluate candidate products. Vaccine candidates are evaluated using these NHP models, and through this public–private partnership, a meta-analysis of NHP control data has been conducted and submitted to the FDA as a master file. This is an example of how existing NHP control data can be leveraged in lieu of conducting separate natural history studies at multiple testing facilities to demonstrate the consistency of a standardized animal model for vaccine development. As a result, animal use can be minimized and the duplication of effort avoided, thus reducing the amount of time needed to conduct additional studies, as well as the cost of vaccine candidate development. This successful strategy may be applied to other pathogens of high consequence for vaccine development, and shows how strategic preparedness for biodefense can be leveraged in response to outbreaks and public health emergencies.

A bivalent Adenovirus-Vectored Vaccine induces a robust humoral response, but does not protect cynomolgus macaques against a lethal challenge with Sudan virus

“…A second EBOV vaccine approved by the European Medical Agency utilizes a prime-boost approach of replication-incompetent adenovirus (Ad26) encoding the EBOV Mayinga GP (Ad26.ZEBOV, Zabdeno) followed by non-replicating modified vaccinia Ankara–vectored vaccine encoding the EBOV Mayinga, SUDV Gulu, and MARV Musoke GPs and the nucleoprotein of the Tai Forest virus (MVA-BN-Filo, Mvabea). The animal rule regulatory pathway, which allows for efficacy data generated in well-characterized animal models of human disease to demonstrate effectiveness in place of phase II or III efficacy trails in humans, facilitated the licensure of the Zabdeno/Mvabea prime-boost vaccination regimen ( 13 ). This two-shot vaccination is efficacious against SUDV in non-human primates (NHPs) ( 14 ), but the effectiveness against SVD in humans is unknown.…”

“…The copyright holder for this preprint this version posted October 21, 2023. ; https://doi.org/10.1101/2023.10.20.563337 doi: bioRxiv preprint facilitated the licensure of the Zabdeno/Mvabea prime-boost vaccination regimen (13). This twoshot vaccination is efficacious against SUDV in non-human primates (NHPs) (14), but the effectiveness against SVD in humans is unknown.…”