A Novel Rabies Vaccine Based on a Recombinant Parainfluenza Virus 5 Expressing Rabies Virus Glycoprotein

Chen, Zhenhai; Zhou, Ming; Gao, Xiaorong; Zhang, Guoqing; Ren, Guangxin; Gnanadurai, Clement W.; Fu, Zhen F.; He, Biao

doi:10.1128/jvi.02886-12

Cited by 49 publications

(43 citation statements)

References 33 publications

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“…Currently, kennel cough vaccines are mass produced by major veterinary vaccine companies. Fourth, a PIV5-vectored vaccine has been shown to be efficacious in animals (28)(29)(30)(31)(32). In our recent studies, we have found that a single-dose intranasal (i.n.)…”

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confidence: 99%

Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses

Gabbard

Mooney

et al. 2013

J Virol

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confidence: 99%

Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses

Gabbard

Mooney

et al. 2013

J Virol

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“…PIV5 can infect humans and animals without causing any known symptoms or diseases (3,4). It has been used as a vector for vaccine development (5)(6)(7)(8)(9)(10)(11).…”

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confidence: 99%

Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5

Yang

Zengel

Sun

et al. 2015

J Virol

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Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. IMPORTANCEWe identified two regions of the V protein that interact with NP and determined that one of these regions enhances viral RNA transcription via its interaction with NP. Our data suggest that a common host factor may be involved in the regulation of paramyxovirus replication and could be a target for broad antiviral drug development. Understanding the regulation of paramyxovirus replication will enable the rational design of vaccines and potential antiviral drugs. The family Paramyxoviridae belongs to the Mononegavirales and has two subfamilies, the Paramyxovirinae and the Pneumovirinae. The subfamily Paramyxovirinae contains five genera: Rubulavirus, Respirovirus, Morbillivirus, Avulavirus, and Henipavirus. The subfamily Pneumovirinae contains two genera: Pneumovirus and Metapneumovirus. This virus family includes many wellknown human and animal pathogens, such as mumps virus (MuV), which belongs to the genus Rubulavirus; Sendai virus (SeV) and human parainfluenza virus 3 (PIV3), which belong to the genus Respirovirus; measles virus (MV), which belongs to the genus Morbillivirus; and emerging viruses like Nipah virus (NiV), which belongs to the genus Henipavirus (1). Parainfluenza virus 5 (PIV5), formerly known as simian virus 5 (SV5) (2), is a prototypical paramyxovirus and belongs to the Rubulavirus genus in the Paramyxoviridae family. PIV5 can infect humans and animals without causing any known symptoms or diseases (3, 4). It has been used as a vector for vaccine development (5-11).The PIV5 genome consists of a nonsegmented negativestranded RNA which is encapsidated by the nucleocapsid (NP) protein (1). The viral RNA polymerase (vRNAP) complex that contains the large (L) protein and the phosphoprotein (P) transcribes the NP-encapsidated genome RNA into 5=-capped and 3=-polyadenylated mRNAs. vRNAP starts viral RNA synthesis at the 3= end of the genome, and it transcribes the genes into mRNAs in a sequential (and polar) manner by terminating and reinitiating transcription at each of the gene junctions (1). vRNAP also replicates the RNA genome by making an exact copy of the genome from negative-sense RNA to positive-sense RNA and from positive-sense RNA back to negative-sense RNA. Viral RNA transcription occurs first after infection to allow the production of viral proteins, and viral RNA replication follows (1). PIV5 is an enveloped virus and enters the cell by fusing with the plasma mem-

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“…It induces virus-neutralizing antibody and protects animals against subsequent RV infection [1,5,26]. As G is the major antigen of RV, various vaccines expressing G alone such as DNA-based rabies vaccines and live recombinant vectors have successfully elicited strong protective immune responses [6,8,28,29]. A modified G may induce a stronger immune reaction: administration of a DNA vaccine expressing ERA G with R333Q resulted in a higher VNA than the unmodified G [16].…”

Section: Discussionmentioning

confidence: 99%

“…Two weeks after the third vaccination, blood was collected for assay of NA to CDV (a) and RV (b). RV NA titer was converted to international units (IU) by comparison with a WHO standard serum Virus Genes RV G [6,8]. CDV also has shown its potential as an effective vaccine vector for RV [27].…”

Section: Discussionmentioning

confidence: 99%

A recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice

Wang

Ding

et al. 2015

Virus Genes

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Canine distemper virus (CDV) and rabies virus (RV) are two important pathogens of the dog. CDV, a member of the morbillivirus genus, has shown promise as an expression vector. The glycoprotein from RV is a main contributor to protective immunity and capable of eliciting the production of virus-neutralizing antibodies. In this study, we recovered an attenuated strain of canine distemper virus and constructed a recombinant virus, rCDV-RV-G, expressing a modified (R333Q) rabies virus glycoprotein (RV-G) of RV Flury strain LEP. RV-G expression by the recombinant viruses was confirmed. Furthermore, G was proved to be incorporated into the surface of CDV particles. While replication of the recombinant virus was slightly reduced compared with the parental CDV, it stably expressed the RV-G over ten serial passages. Inoculation of mice induced specific neutralizing antibodies against both RV-G and CDV. Therefore, the rCDV-RV-G has the potential as a vaccine that may be used to control rabies virus infection in dogs and other animals.

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A Novel Rabies Vaccine Based on a Recombinant Parainfluenza Virus 5 Expressing Rabies Virus Glycoprotein

Cited by 49 publications

References 33 publications

Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses

Single-Dose Vaccination of a Recombinant Parainfluenza Virus 5 Expressing NP from H5N1 Virus Provides Broad Immunity against Influenza A Viruses

Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5

A recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice

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