Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production

Tao, Lihong; Ge, Jinying; Wang, Xijun; Wen, Zhiyuan; Zhai, Hongyue; Tao, Hua; Zhao, Bolin; Kong, Dongni; Yang, Chinglai; Bu, Zhigao

doi:10.1186/1743-422x-8-454

Cited by 21 publications

(10 citation statements)

References 18 publications

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“…The improvement of immunogenicity and the loss of pathogenicity make SPBNGA-GA an excellent candidate strain for a modified live vaccine. Tao et al [80] established the reverse genetic system for the LEP strain and produced recombinant LEP virus (rLEP-G) carrying two identical G genes. The VNA titer of the inactivated vaccine produced by rLEP-G in mice and dogs was significantly higher than that of the LEP-derived vaccine.…”

Section: The Development Of Attenuated Rabies Vaccinesmentioning

confidence: 99%

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems

Yin

Wang

Mao

et al. 2021

Viruses

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Rabies is a lethal zoonotic disease caused by lyssaviruses, such as rabies virus (RABV), that results in nearly 100% mortality once clinical symptoms appear. There are no curable drugs available yet. RABV contains five structural proteins that play an important role in viral replication, transcription, infection, and immune escape mechanisms. In the past decade, progress has been made in research on the pathogenicity of RABV, which plays an important role in the creation of new recombinant RABV vaccines by reverse genetic manipulation. Here, we review the latest advances on the interaction between RABV proteins in the infected host and the applied development of rabies vaccines by using a fully operational RABV reverse genetics system. This article provides a background for more in-depth research on the pathogenic mechanism of RABV and the development of therapeutic drugs and new biologics.

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Section: The Development Of Attenuated Rabies Vaccinesmentioning

confidence: 99%

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems

Yin

Wang

Mao

et al. 2021

Viruses

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“…Cistrons encoding the structural envelope proteins, which are the principal targets of protective neutralizing immunity, are located in the second-or third-to-last positions of the genomes of paramyxoviruses, resulting in relatively low expression levels (16). Envelope protein expression can be augmented by increasing the copy number of their coding cistrons and/or by moving these cistrons proximally within the viral genome (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). To develop an MV vaccine containing a greater immunogenic stimulus within the standard WHO-approved dosage, we constructed two recombinant MVs that express an additional copy of the hemagglutinin (H) protein in a membrane-bound or soluble form from the second position of a Moraten strain-equivalent genome, resulting in increased expression and incorporation or secretion of H while maintaining replicative fitness and stability.…”

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confidence: 99%

Generation of a More Immunogenic Measles Vaccine by Increasing Its Hemagglutinin Expression

Julik

Valle

2016

J Virol

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Imported measles virus (MV) outbreaks are maintained by poor vaccine responders and unvaccinated people. A convenient but more immunogenic vaccination strategy would enhance vaccine performance, contributing to measles eradication efforts. We report here the generation of alternative pediatric vaccines against MV with increased expression of the H protein in the background of the current MV vaccine strain. We generated two recombinants: MVvac2-H2, with increased full-length H expression resulting in a 3-fold increase in H incorporation into virions, and MVvac2-Hsol, vectoring a truncated, soluble form of the H protein that is secreted into the supernatants of infected cells. Replication fitness was conserved despite the duplication of the H cistron for both vectors. The modification to the envelope of MVvac2-H2 conferred upon this virus a measurable level of resistance to in vitro neutralization by MV polyclonal immune sera without altering its thermostability. Most interestingly, both recombinant MVs with enhanced H expression were significantly more immunogenic than their parental strain in outbred mice, while MVvac2-H2 additionally proved more immunogenic after a single, human-range dose in genetically modified MV-susceptible mice. IMPORTANCEMeasles incidence was reduced drastically following the introduction of attenuated vaccines, but progress toward the eradication of this virus has stalled, and MV still threatens unvaccinated populations. Due to the contributions of primary vaccine failures and too-young-to-be-vaccinated infants to this problem, more immunogenic measles vaccines are highly desirable. We generated two experimental MV vaccines based on a current vaccine's genome but with enriched production of the H protein, the main MV antigen in provoking immunity. One vaccine incorporated H at higher rates in the viral envelope, and the other secreted a soluble H protein from infected cells. The increased expression of H by these vectors improved neutralizing responses induced in two small-animal models of MV immunogenicity. The enhanced immunogenicity of these vectors, mainly from the MV that incorporates additional H, suggests their value as potential alternative pediatric MV vaccines. Despite the existence of an effective vaccine, measles virus (MV) infections remain an insidious threat to global health. After decades of reduction in measles-related mortality due to vaccination, this has stalled at between 110,000 and 120,000 deaths/year since 2012. Approximately 20 million people are infected by measles each year, with significant morbidity and up to 1% mortality (1). In 2014, the United States saw the highest number of annual measles cases since native transmission was declared locally eliminated in 2000 (2) and experienced a large multistate outbreak in the first months of 2015 (3).Protecting young infants against measles is an important goal to attain to improve the current MV vaccine (4). The highest fatality rates due to MV infection occur in infants Ͻ1 year of age (5). Ironically, incre...

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“…Scientists attempt to improve vaccine quality by developing epitope-based and nucleic acid-based vaccines, virus-like particles, simian adenovirus-based vaccines, and chimeric rabies vaccines [20][21][22][23]. Consequently, certain efforts have been made successfully to improve the virus immunogenicity by concentrating on gene duplications [14,24]. The glycoprotein of the rabies virus has a fundamental role in virus attachment and infectivity as well as inducing the host's antiviral immune response [25,26]; therefore, an increase in the virus glycoprotein can inherently enhance the host defense mechanism.…”

Section: Discussionmentioning

confidence: 99%

The Double Glycoprotein Rabies Virus Strain Shows Increased Propagation Rate and Boosted Immunogenicity.

Alamdary

Gholami

Azizi

et al. 2022

Preprint

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Background Rabies is a neurotropic virus that causes about 59000 deaths worldwide annually. The most effective means to control and prevent rabies is prevention through proper pre- and post-exposure vaccination. Glycoprotein (G) is one of five structural proteins of the rabies virus and has a pivotal role in host immunity against the virus. This research has evaluated the results of incorporating an additional copy of the glycoprotein gene in the rabies virus genome on the immunogenicity and propagation rate of the recombinant virus. Methods . A PCR amplified copy of the G gene was previously inserted into the genome of the rabies virus PV strain. The recombinant virus glycoprotein expression was compared with the PV strain. The propagation rate of the recombinant virus in cell culture and its immunogenicity in BALB/c mice were assessed. The rapid fluorescent focus inhibition test (RFFIT) was used to analyze the virus-neutralizing antibodies (VNAs) in the mice sera. Results The addition of an extra G gene between the G and L genes was verified in the rescued recombinant virus. The virus strain carrying two G (dG) showed significantly higher virus titers and glycoprotein expression levels in cell culture and also induced higher titers of VNAs when applied in mice as an experimental vaccine. Conclusion Our results suggest that duplication of the G gene in the PV virus genome between G, and L genes leads to increased G expression level, higher virus propagation rates and improved VNA induction. The recombinant dG strain might be characterized for application in rabies vaccine production, and it can also be used to study different cellular pathways related to the rabies virus cycle.

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Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production

Cited by 21 publications

References 18 publications

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems

Research Advances on the Interactions between Rabies Virus Structural Proteins and Host Target Cells: Accrued Knowledge from the Application of Reverse Genetics Systems

Generation of a More Immunogenic Measles Vaccine by Increasing Its Hemagglutinin Expression

The Double Glycoprotein Rabies Virus Strain Shows Increased Propagation Rate and Boosted Immunogenicity.

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