A single dose investigational subunit vaccine for human use against Nipah virus and Hendra virus

Timothy R Fouts,Kathryn Bobb,Viktoriya Borisevich,Thomas W Geisbert,Abhishek N Prasad,Joan B Geisbert,Robert W Cross,Karla A Fenton,Krystle N Agans,Christopher C Broder,Antony S Dimitrov,Hao Yu

doi:10.1038/s41541-021-00284-w

Abstract

Nipah and Hendra viruses are highly pathogenic bat-borne paramyxoviruses recently included in the WHO Blueprint priority diseases list. A fully registered horse anti-Hendra virus subunit vaccine has been in use in Australia since 2012. Based on the same immunogen, the Hendra virus attachment glycoprotein ectodomain, a subunit vaccine formulation for use in people is now in a Phase I clinical trial. We report that a single dose vaccination regimen of this human vaccine formulation protects against otherwise lethal challenges of either Hendra or Nipah virus in a nonhuman primate model. The protection against the Nipah Bangladesh strain begins as soon as 7 days post immunization with low dose of 0.1 mg protein subunit. Our data suggest this human vaccine could be utilized as efficient emergency vaccine to disrupt potential spreading of Nipah disease in an outbreak setting.

Highlights

Nipah virus (NiV) and Hendra virus (HeV) are enveloped, singlestranded negative-sense RNA viruses and the prototype members of the genus Henipavirus in the family Paramyxoviridae1
There have been more than 10 NiV/HeV vaccine and challenge studies to date which have included several virus vectored strategies, virus-like-particles, mRNA, and recombinant protein subunits in a number of different animal models10,17,25
It appeared this subject developed protective efficacy against NiV from Malaysia (NiV-M) and NiV Bangladesh (NiV-B) in at least three animal central nervous system (CNS) clinical signs starting on day 20, this observation may not models including nonhuman primates, and because of the have been related to the virus challenge for the following reasons: inherent safety of a recombinant subunit protein immunogen (i) viral RNA was not detected in plasma; (ii) viral RNA was modality, and its effectiveness and success as a One-Health detected in 2 tissue samples; it was in line with vaccine approach against the NiV/HeV transboundary viral threats27

Summary

Introduction

Nipah virus (NiV) and Hendra virus (HeV) are enveloped, singlestranded negative-sense RNA viruses and the prototype members of the genus Henipavirus in the family Paramyxoviridae. In several animal species and in people, the major pathological observations of NiV and HeV infection is a severe systemic and often fatal neurologic and/or respiratory disease. In several animal species and in people, the major pathological observations of NiV and HeV infection is a severe systemic and often fatal neurologic and/or respiratory disease3–5 Both NiV and HeV can cause relapsing encephalitis, from several months to more than 10 years later, following a recovery from an acute infection as a result of recrudescence of virus replication in the central nervous system (CNS). HeV was first recognized in 1994 as the cause of an outbreak that led to fatal cases of severe respiratory disease in horses and humans in the Brisbane suburb of Hendra, Australia.

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Conclusion