A Hendra Virus G Glycoprotein Subunit Vaccine Protects African Green Monkeys from Nipah Virus Challenge

Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection.

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Feline Model of Acute Nipah Virus Infection and Protection with a Soluble Glycoprotein-Based Subunit Vaccine

Journal of Virology ◽

10.1128/jvi.01619-06 ◽

2006 ◽

Vol 80 (24) ◽

pp. 12293-12302 ◽

Cited By ~ 105

Author(s):

Bruce A. Mungall ◽

Deborah Middleton ◽

Gary Crameri ◽

John Bingham ◽

Kim Halpin ◽

...

Keyword(s):

Subunit Vaccine ◽

Case Reports ◽

Mammalian Species ◽

Nipah Virus ◽

Disease Onset ◽

Hendra Virus ◽

Clinical Disease ◽

Pcr Analysis ◽

Wide Range ◽

Feline Model

ABSTRACT Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. Case reports from outbreaks and previous challenge experiments have suggested that cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 50% tissue culture infective dose(s) (TCID50) of NiV. Animals were monitored closely for disease onset, and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6 to 9 days postinfection, a finding consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two were immunized with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000, and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naive controls were then challenged subcutaneously with 500 TCID50 of NiV. Naive animals developed clinical disease 6 to 13 days postinfection, whereas none of the immunized animals showed any sign of disease. TaqMan PCR analysis of samples from naive animals revealed considerable levels of NiV genome in a wide range of tissues, whereas the genome was evident in only two immunized cats in only four samples and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.

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Evaluation of a Single-Dose Nucleoside-Modified Messenger RNA Vaccine Encoding Hendra Virus-Soluble Glycoprotein Against Lethal Nipah virus Challenge in Syrian Hamsters

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz553 ◽

2019 ◽

Vol 221 (Supplement_4) ◽

pp. S493-S498 ◽

Cited By ~ 3

Author(s):

Michael K Lo ◽

Jessica R Spengler ◽

Stephen R Welch ◽

Jessica R Harmon ◽

JoAnn D Coleman-McCray ◽

...

Keyword(s):

Single Dose ◽

Immune Responses ◽

Messenger Rna ◽

Nipah Virus ◽

Hendra Virus ◽

Highly Pathogenic ◽

Syrian Hamsters ◽

Virus Challenge ◽

Pathogenic Viruses ◽

Rna Vaccine

Abstract In the absence of approved vaccines and therapeutics for use in humans, Nipah virus (NiV) continues to cause fatal outbreaks of encephalitis and respiratory disease in Bangladesh and India on a near-annual basis. We determined that a single dose of a lipid nanoparticle nucleoside-modified messenger RNA vaccine encoding the soluble Hendra virus glycoprotein protected up to 70% of Syrian hamsters from lethal NiV challenge, despite animals having suboptimally primed immune responses before challenge. These data provide a foundation from which to optimize future messenger RNA vaccination studies against NiV and other highly pathogenic viruses.

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A Recombinant Hendra Virus G Glycoprotein Subunit Vaccine Protects Nonhuman Primates against Hendra Virus Challenge

Journal of Virology ◽

10.1128/jvi.00005-14 ◽

2014 ◽

Vol 88 (9) ◽

pp. 4624-4631 ◽

Cited By ~ 27

Author(s):

C. E. Mire ◽

J. B. Geisbert ◽

K. N. Agans ◽

Y.-R. Feng ◽

K. A. Fenton ◽

...

Keyword(s):

Subunit Vaccine ◽

Nonhuman Primates ◽

Hendra Virus ◽

Virus Challenge

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

npj Vaccines ◽

10.1038/s41541-021-00284-w ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Thomas W. Geisbert ◽

Kathryn Bobb ◽

Viktoriya Borisevich ◽

Joan B. Geisbert ◽

Krystle N. Agans ◽

...

Keyword(s):

Single Dose ◽

Subunit Vaccine ◽

Nipah Virus ◽

Hendra Virus ◽

Vaccine Formulation ◽

Protein Subunit ◽

Primate Model ◽

Virus Attachment ◽

A Subunit ◽

Human Vaccine

AbstractNipah 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.

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