rVSV-ΔG-EBOV-GP-Nipah-G (also designated PHV02) replication-competent, recombinant vesicular stomatitis virus vaccine for prevention of Nipah virus disease: Standardized template with key considerations for a risk/benefit assessment.

A recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (GP) of Ebola virus (rVSV-EBOV GP) has been approved for preventive immunization against Ebola (Ervebo®, Merck & Co.). The rVSV-EBOV vector was modified to express an additional glycoprotein (G) of Nipah virus (NiV), a bat-borne henipavirus endemic/epidemic in South and Southeast Asia that causes fatal encephalitis and pneumonia. The rVSV-EBOV-GP-NiV G vaccine candidate ("PHV02") is a unique chimeric virus with tropism and immunological properties derived from the wild-type (wt) vesicular stomatitis virus (VSV) parent, the rVSV-EBOV-GP vector and the NiV G transgene donor. The EBOV GP enables fusion with the cell membrane and virus entry, whereas the NiV G protein mediates attachment to cells and serves as the antigen for stimulating NiV-specific immunity. This review focuses on the characteristics of the vector and vaccine candidate relevant to clinical and environmental safety, immunogenicity and efficacy. The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) standardized template is used to update the key characteristics and risks of the rVSV-EBOV vector (previously published [1]) and the novel PHV02 NiV vaccine candidate which is now in clinical trials. The template provides a rich source of information and guide to the supporting literature. While analogies of the PHV02 NiV vaccine to the backbone rVSV-EBOV vector are useful given the more extensive data available on the vector, the template emphasizes that PHV02 is a novel construct from a regulatory perspective and targets a different disease with unique characteristics and pathogenesis. Where similarities and parallels are drawn between nonclinical and clinical outcomes of rVSV-EBOV (vector) and PHV02 (vaccine), the reader should be cognizant of the limitations of these conclusions. The intended use of the standardized template is to provide a cohesive reference allowing vaccine developers and regulatory reviewers to understand characteristics, benefits and risks of a new vaccine candidate against NiV relevant to its future use in human populations, and to compare and contrast these characteristics to an approved vaccine constructed from the same (rVSV) vector system against a different indication (ebolavirus). The systematized template structure should facilitate utility of the paper.