Multivalent viral particles elicit safe and efficient immunoprotection against Nipah Hendra and Ebola viruses

Abstract

Experimental vaccines for the deadly zoonotic Nipah (NiV), Hendra (HeV), and Ebola (EBOV) viruses have focused on targeting individual viruses, although their geographical and bat reservoir host overlaps warrant creation of multivalent vaccines. Here we explored whether replication-incompetent pseudotyped vesicular stomatitis virus (VSV) virions or NiV-based virus-like particles (VLPs) were suitable multivalent vaccine platforms by co-incorporating multiple surface glycoproteins from NiV, HeV, and EBOV onto these virions. We then enhanced the vaccines’ thermotolerance using carbohydrates to enhance applicability in global regions that lack cold-chain infrastructure. Excitingly, in a Syrian hamster model of disease, the VSV multivalent vaccine elicited safe, strong, and protective neutralizing antibody responses against challenge with NiV, HeV, or EBOV. Our study provides proof-of-principle evidence that replication-incompetent multivalent viral particle vaccines are sufficient to provide protection against multiple zoonotic deadly viruses with high pandemic potential.

Establishment of a Nipah Virus Disease Model in Hamsters, including a Comparison of Intranasal and Intraperitoneal Routes of Challenge

“…route appears more uniform compared to the i.n. route [ 21 ], and is the main reported route of challenge for efficacy testing of NiV vaccine candidates [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ] and antivirals [ 38 ]. Whilst we did not assess aerosol exposure, it was reported that this route does not change the course of disease compared to i.n.…”

Two Point Mutations in the Glycoprotein of SFTSV Enhance the Propagation Recombinant Vesicular Stomatitis Virus Vectors at Assembly Step

“…By replacing the original G glycoprotein with those of the target viruses, the recombinant VSV virus displays the heterologous glycoprotein on the surface, which can trigger a robust immune response. Many virus groups are successfully recombined with VSV, including filoviruses, bunyaviruses, paramyxoviruses, and arenaviruses [ 38 , 46 , 48 , 49 ]. However, the titers of many recombinant VSV-vector viruses are not high enough for large-scale production, which is critical for vaccine development.…”

Strategic vaccine stockpiles for regional epidemics of emerging viruses: a geospatial modeling framework

“…A number of vaccine candidates are already in various stages of development and clinical trials for both MERS-CoV and Nipah virus (Foster et al 2022; van Doremalen et al 2019; Bosaeed et al 2022; Modjarrad et al 2019; Alharbi et al 2017; Ithinji et al 2022), but so far, none have been licensed for use in human populations. Given the resulting uncertainty, and for modeling simplicity, we assumed a one-dose regimen for both vaccines, and that vaccination results in sterilizing immunity (vaccinated individuals are no longer susceptible), but also assume that immunity takes time to be conferred, that efficacy is less than 100%, and that there could be delays in vaccine availability after public health response is first mobilized.…”