Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection

Schwartz, Jennifer A.; Buonocore, Linda; Roberts, Anjeanette; Suguitan, Amorsolo L.; Kobasa, Darwyn; Kobinger, Gary P.; Feldmann, Heinz; Subbarao, Kanta; Rose, John K.

doi:10.1016/j.virol.2007.04.021

Cited by 54 publications

(82 citation statements)

References 41 publications

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“…In order to examine the effect of L111F mutation on the release of the virus particles from the infected cells, we first checked the burst sizes of the new M mutants and compared them to that of the wild-type rVSV Ind strain. First, the burst sizes of the viruses were determined in BHK 21 cells at 10 h postinfection with a virus MOI of 3 at both permissive (31°C) and semipermissive (37°C) temperatures. The rVSV Ind (GL) and rVSV Ind (GML) mutants produced 100-fold less infectious virus particles at 37°C than at 31°C, demonstrating the temperature sensitivity of the mutants in the release of virus particles at 37°C (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…The temperature sensitivities of the newly generated M mutants of rVSV NJ were examined by infecting BHK 21 The mutations in the M gene were introduced by site-directed mutagenesis using the megaprimer PCR method, and the PCR products were cloned into PacI and NotI sites to replace the wild-type M gene in both rVSV Ind and rVSV NJ . The format used shows the original amino acid before the number followed by the mutated amino acid after the number.…”

Section: Resultsmentioning

confidence: 99%

“…rVSVs with the G gene deleted (⌬G) and with single-cycle replication in regular cells and in the animal host were developed, and the ⌬G rVSV was amplified in the VSV G protein-expressing cell line (20)(21)(22). This approach renders approximately a 2-log reduction of virus production, and it may produce inadequate quantities of virus for the preparation of live recombinant virus vaccines, should the vaccination require a high dose of virus.…”

Section: Esicular Stomatitis Virus (Vsv) Is a Rapidly Replicating Vmentioning

confidence: 99%

“…BSR T7/5 cells (30) were obtained from K. K. Conzelmann. The BHK 21 cells constitutively expressing bacteriophage T7 RNA polymerase were grown in DMEM containing 5% FBS and 500 g/ml G418 (Invitrogen).…”

Section: Cellsmentioning

confidence: 99%

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Creation of Matrix Protein Gene Variants of Two Serotypes of Vesicular Stomatitis Virus as Prime-Boost Vaccine Vectors

Kim

Hong

et al. 2015

J Virol

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To take advantage of live recombinant vesicular stomatitis viruses (rVSVs) as vaccine vectors for their high yield and for their induction of strong and long-lasting immune responses, it is necessary to make live vaccine vectors safe for use without losing their immunogenicity. We have generated safer and highly efficient recombinant VSV vaccine vectors by combining the M51R mutation in the M gene of serotype VSV-Indiana (VSV Ind ) with a temperature-sensitive mutation (tsO23) of the VSV Ind Orsay strain. In addition, we have generated two new serotype VSV-New Jersey (VSV NJ ) vaccine vectors by combining M48R and M51R mutations with G22E and L110F mutations in the M gene, rVSV NJ (G22E M48R M51R) [rVSV NJ (GMM)] and VSV NJ (G22E M48R M51R L110F) [rVSV NJ (GMML)]. The combined mutations G21E, M51R, and L111F in the M protein of VSV Ind significantly reduced the burst size of the virus by up to 10,000-fold at 37°C without affecting the level of protein expression. BHK 21 cells and SH-SY5Y human neuroblastoma cells infected with rVSV Ind (GML), rVSV NJ (GMM), and rVSV NJ (GMML) showed significantly reduced cytopathic effects in vitro at 37°C, and mice injected with 1 million infectious virus particles of these mutants into the brain showed no neurological dysfunctions or any other adverse effects. In order to increase the stability of the temperaturesensitive mutant, we have replaced the phenylalanine with alanine. This will change all three nucleotides from UUG (leucine) to GCA (alanine). The resulting L111A mutant showed the temperature-sensitive phenotype of rVSV Ind (GML) and increased stability. Twenty consecutive passages of rVSV Ind (GML) with an L111A mutation did not convert back to leucine (UUG) at position 111 in the M protein gene. V esicular stomatitis virus (VSV) is a rapidly replicating virus.Eventually humoral and cellular immune responses against VSV are elicited in the animal host, like any other viral vectors (1-3). Animals infected with VSV develop immune responses within 2 weeks and start to neutralize the VSV (1). This hinders the efficacy of boost immunizations for vaccination with the same vector. Serotype-specific antibodies against the viral surface glycoprotein G neutralize VSV. Two different serotypes of VSV, VSV-Indiana (VSV Ind ) and VSV-New Jersey (VSV NJ ), show 50% amino acid homologies in glycoprotein G (4). Antibodies raised against one serotype of VSV do not neutralize the other serotype of VSV (5). Accordingly, other investigators have used VSV Ind with its own surface glycoprotein G and VSV Ind carrying the G gene from other serotypes as a vaccine vector (6, 7).VSV causes self-limiting disease in animals such as pigs, cows, and horses, whereby vesicular lesions on the mouth, nose, teats, and hooves are cleared in a couple of weeks after the onset (8).Although it is very rare, human infections with VSV have been reported mostly in animal care workers, veterinarians, and laboratory personnel who were in close contact with the diseased animals or with the viruses (9-11)....

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Esicular Stomatitis Virus (Vsv) Is a Rapidly Replicating Vmentioning

confidence: 99%

Section: Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Creation of Matrix Protein Gene Variants of Two Serotypes of Vesicular Stomatitis Virus as Prime-Boost Vaccine Vectors

Kim

Hong

et al. 2015

J Virol

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“…On one hand, it is possible that some cytotoxic properties still remain with this virus. On the other hand, the possibility that IFN-independent innate immune mechanisms exist that were able to restrict VSV replication cannot be excluded.VSVDG replicons have been used successfully as experimental vaccine vectors (Kahn et al, 2001;Kalhoro et al, 2009;Kapadia et al, 2008;Majid et al, 2006;Publicover et al, 2005;Roberts et al, 1999a;Schwartz et al, 2007). These replicon vaccines express the wild-type M protein and are highly cytotoxic.…”

mentioning

confidence: 99%

Fusion-active glycoprotein G mediates the cytotoxicity of vesicular stomatitis virus M mutants lacking host shut-off activity

Hoffmann

Gerber

et al. 2010

Journal of General Virology

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The cytopathogenicity of vesicular stomatitis virus (VSV) has been attributed mainly to the host shut-off activity of the viral matrix (M) protein, which inhibits both nuclear transcription and nucleocytoplasmic RNA transport, thereby effectively suppressing the synthesis of type I interferon (IFN). The M protein from persistently VSV-infected cells was shown to harbour characteristic amino acid substitutions (M51R, V221F and S226R) implicated in IFN induction. This study demonstrates that infection of human fibroblasts with recombinant VSV containing the M51R substitution resulted in IFN induction, whereas neither the V221F nor the S226R substitution effected an IFN-inducing phenotype. Only when V221F was combined with S226R were the host shut-off activity of the M protein abolished and IFN induced, independently of M51R. The M33A substitution, previously implicated in VSV cytotoxicity, did not affect host shutoff activity. M-mutant VSV containing all four amino acid substitutions retained cytotoxic properties in both Vero cells and IFN-competent primary fibroblasts. Infected-cell death was associated with the formation of giant polynucleated cells, suggesting that the fusion activity of the VSV G protein was involved. Accordingly, M-mutant VSV expressing a fusion-defective G protein or with a deletion of the G gene showed significantly reduced cytotoxic properties and caused long-lasting infections in Vero cells and mouse hippocampal slice cultures. In contrast, a G-deleted VSV expressing wild-type M protein remained cytotoxic. These findings indicate that the host shut-off activity of the M protein dominates VSV cytotoxicty, whilst the fusion-active G protein is mainly responsible for the cytotoxicity remaining with M-mutant VSV. INTRODUCTIONVesicular stomatitis virus (VSV) is a prototype member of the family Rhabdoviridae. The virus genome is composed of a non-segmented, single-strand, negative-sense RNA encoding five genes, which are arranged in a module-like, non-overlapping manner. The RNA genome combines with the nucleoprotein N, the phosphoprotein P and the large protein L to form the helical ribonucleoprotein (RNP) complex. This complex is connected to the envelope via the matrix protein M, which binds to both the N protein and the inner leaflet of the lipid-bilayer membrane (Dancho et al., 2009). The M protein plays a key role in VSV morphogenesis and budding (Jayakar et al., 2004).The VSV envelope contains a single-type transmembrane glycoprotein (G), which has receptor-binding and fusion activities. Following uptake of the virion by receptormediated endocytosis and acidification of the endosome, the G protein can perform fusion between the membranes of the viral envelope and the endosome. This results in the release of the RNP complex into the cytosol, where transcription and replication take place. In addition to its role in virus entry, the G protein is important for efficient virus budding and release (Jeetendra et al., 2003).VSV shows a very broad cell tropism and replicates rapidly in various c...

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Measles

2009

Current Topics in Microbiology and Immunology

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Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection

Cited by 54 publications

References 41 publications

Creation of Matrix Protein Gene Variants of Two Serotypes of Vesicular Stomatitis Virus as Prime-Boost Vaccine Vectors

Creation of Matrix Protein Gene Variants of Two Serotypes of Vesicular Stomatitis Virus as Prime-Boost Vaccine Vectors

Fusion-active glycoprotein G mediates the cytotoxicity of vesicular stomatitis virus M mutants lacking host shut-off activity

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