Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters

Lo, Michael K.; Bird, Brian H.; Chattopadhyay, Anasuya; Drew, Clifton P.; Martin, Brock E.; Coleman, Joann D.; Rose, John K.; Nichol, Stuart T.; Spiropoulou, Christina F.

doi:10.1016/j.antiviral.2013.10.012

Cited by 66 publications

(47 citation statements)

References 35 publications

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“…This stands in contrast to findings with virus-like particles, where protection in mice against lethal filovirus challenge requires either a regimen of a prime and two boosts or the presence of adjuvants (9, 42, 50-52). VSVΔG SRIPs bearing the glycoprotein from other highly pathogenic viruses such as Nipah virus have also been demonstrated to serve as a protective vaccine (53,54). It is thought that one or more VSV proteins have adjuvant-like properties, thereby eliciting robust adaptive immune responses to the vaccine immunogen (21,55,56), although which VSV protein(s) is important for this enhancing effect has not been identified.…”

Section: Discussionmentioning

confidence: 99%

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

Lennemann

Herbert

Brouillette

et al. 2017

J Virol

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The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success.IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.

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Section: Discussionmentioning

confidence: 99%

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

Lennemann

Herbert

Brouillette

et al. 2017

J Virol

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“…All the chimeric viruses discussed here have shown efficacy in acting in a vaccine capacity to protect against the respective virus antigens, including Nipah virus, chikungunya virus, and influenza virus (44,(46)(47)(48)(49). By virtue of their safety in both adult and developing brains, VSVΔG-CHIKV and VLV showed the least adverse neurotropism among the chimeric viruses tested; these viruses merit further investigation for potential applications, including vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…The VSV glycoprotein gene was deleted (VSVΔG) in four of the viruses, VSVΔG-CHIKV, VSVΔG-H5N1, VSVΔG-Nipah F, and VSVΔG-Nipah G. VLV was generated from the Semliki Forest virus RNA replicon encoding VSV G and the four nonstructural proteins of SFV but none of the SFV structural proteins (37,39). All four recombinants have been tested as possible vaccine vectors (38,(44)(45)(46)(47)(48)(49). Three additional recombinant VSVs were used for control purposes; all three have been previously used to test intracranial safety (18,41,50).…”

Section: Resultsmentioning

confidence: 99%

“…Having different VSV recombinants each expressing only one Nipah glycoprotein, however, appears safe. Nonspreading VSVΔG-Nipah F or VSVΔG-Nipah G, used separately, generated a protective immune response against Nipah virus (47,48) and in the absence of ongoing replication would be substantially safer and more viable than the combined VSVΔG-Nipah FϩG.…”

Section: Discussionmentioning

confidence: 99%

“…VSVΔG-Nipah FϩG is a combination of the two replicationincompetent VSVs that each express a single Nipah glycoprotein, F or G. This was done by adding together the two replication-incompetent viruses (VSVΔG-Nipah F plus VSVΔG-Nipah G). Whereas each separately does not propagate, together the two recombinants complement each other and generate a replication-competent chimeric virus pair that expresses both VSV F and G on the virus surface (47,48) when both viruses infect the same cell. Each of the two chimeric viruses was initially pseudotyped with the VSV glycoprotein by expanding the respective virus in cells that express the VSV glycoprotein on the surface.…”

Section: Methodsmentioning

confidence: 99%

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Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain

Pol

Mao

Chattopadhyay

et al. 2017

J Virol

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Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein (G) gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here, we test 4 chimeric viruses in the brain, including those in which glycoprotein genes from Nipah, chikungunya (CHIKV), and influenza H5N1 viruses were substituted for the VSV glycoprotein gene. We also test a virus-like vesicle (VLV) in which the VSV glycoprotein gene is expressed from a replicon encoding the nonstructural proteins of Semliki Forest virus. VSVΔG-CHIKV, VSVΔG-H5N1, and VLV were all safe in the adult mouse brain, as were VSVΔG viruses expressing either the Nipah F or G glycoprotein. In contrast, a complementing pair of VSVΔG viruses expressing Nipah G and F glycoproteins were lethal within the brain within a surprisingly short time frame of 2 days. Intranasal inoculation in postnatal day 14 mice with VSVΔG-CHIKV or VLV evoked no adverse response, whereas VSVΔG-H5N1 by this route was lethal in most mice. A key immune mechanism underlying the safety of VSVΔG-CHIKV, VSVΔG-H5N1, and VLV in the adult brain was the type I interferon response; all three viruses were lethal in the brains of adult mice lacking the interferon receptor, suggesting that the viruses can infect and replicate and spread in brain cells if not blocked by interferon-stimulated genes within the brain. IMPORTANCE Vesicular stomatitis virus (VSV) shows considerable promise both as a vaccine vector and as an oncolytic virus. The greatest limitation of VSV is that it is highly neurotropic and can be lethal within the brain. The neurotropism can be mostly attributed to the VSV G glycoprotein. Here, we test 4 chimeric viruses of VSV with glycoprotein genes from Nipah, chikungunya, and influenza viruses and nonstructural genes from Semliki Forest virus. Two of the four, VSVΔG-CHIKV and VLV, show substantially attenuated neurotropism and were safe in the healthy adult mouse brain. VSVΔG-H5N1 was safe in the adult brain but lethal in the younger brain. VSVΔG Nipah FϩG was even more neurotropic than wild-type VSV, evoking a rapid lethal response in the adult brain. These results suggest that while chimeric VSVs show promise, each must be tested with both intranasal and intracranial administration to ensure the absence of lethal neurotropism.

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Recent Advances in Combating Nipah Virus Disease

Chorawala,

Pandya,

Shah

et al. 2024

Rising Contagious Diseases

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Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters

Cited by 66 publications

References 35 publications

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain

Recent Advances in Combating Nipah Virus Disease

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