Construction and biological characterization of artificial recombinants between a wild type flavivirus (Kunjin) and a live chimeric flavivirus vaccine (ChimeriVax-JE)

Пугачев, К. В.; Schwaiger, Jens; Brown, Nathan; Zhang, Zhenxi; Catalan, John; Mitchell, Frederick S.; Ocran, Simeon W.; Rumyantsev, Alexander A.; Khromykh, Alexander A.; Monath, Thomas P.; Guirakhoo, Farshad

doi:10.1016/j.vaccine.2007.07.016

Cited by 16 publications

(8 citation statements)

References 44 publications

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“…These results are consistent with the previous observations that chimeras exhibited growth characteristics similar to those of the viruses contributing structural protein genes (5,41), indicating that the reduction in plaque size and replication efficiency for ChinDENV compared to JEV are likely to be determined partly by the donor prM-E genes. In addition, the chimerization itself has been proved to contribute to the attenuation of chimeras (10,(42)(43)(44)(45)(46)(47)(48)(49)(50). Notably, the chimeric virus ChinDENV replicated efficiently in Vero and PHK cells, both of which are certified for vaccine production.…”

Section: Discussionmentioning

confidence: 99%

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

Deng

Yang

et al. 2013

J Virol

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The development of a safe and efficient dengue vaccine represents a global challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated flavivirus have been well developed as vaccine candidates by using reverse genetics. In this study, based on the full-length infectious cDNA clone of the well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed and constructed by replacement with the premembrane and envelope genes of dengue 2 virus. The recovered chimeric virus showed growth and plaque properties similar to those of the parental DENV in mammalian and mosquito cells. ChinDENV was highly attenuated in mice, and no viremia was induced in rhesus monkeys upon subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation phenotype after serial 15 passages in cultured cells. A single immunization with various doses of ChinDENV elicited strong neutralizing antibodies in a dose-dependent manner. When vaccinated monkeys were challenged with wild-type DENV, all animals except one that received the lower dose were protected against the development of viremia. Furthermore, immunization with Chin-DENV conferred efficient cross protection against lethal JEV challenge in mice in association with robust cellular immunity induced by the replicating nonstructural proteins. Taken together, the results of this preclinical study well demonstrate the great potential of ChinDENV for further development as a dengue vaccine candidate, and this kind of chimeric flavivirus based on JE vaccine virus represents a powerful tool to deliver foreign antigens.

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Section: Discussionmentioning

confidence: 99%

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

Deng

Yang

et al. 2013

J Virol

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“…This creates a selective pressure to accumulate mutants that restore viral fitness by adapting heterologous genomic parts to each other, potentially leading to a loss of attenuation. The accumulation of mutations and genetic stability of flaviviruses were previously reported (Dunster et al, 1999;Laassri et al, 2011;Pugachev et al, 2004;Pugachev et al, 2002;Pugachev et al, 2007).…”

mentioning

confidence: 87%

Microarray Techniques for Evaluation of Genetic Stability of Live Viral Vaccines

Laassri¹,

Cherkasova²,

Abu‐Asab³

et al. 2012

Viral Genomes - Molecular Structure, Diversity, Gene Expression Mechanisms and Host-Virus Interactions

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“…In contrast to some other plus-strand RNA viruses, such as alphaviruses and picornaviruses, flaviviruses are not prone to recombination in nature or experimental settings [50,51]. In addition, several studies that examined “the worst-case scenario” of recombination between ChimeriVax vaccines and wild type JE, Kunjin, DEN4, SLE and YF Asibi viruses indicated that such recombinants, if they ever emerged, would have biological characteristics closer to the highly attenuated YF 17D parent than existing flavivirus pathogens and would be unlikely to successfully compete with endemic flaviviruses for survival in nature [52,53,54]. …”

Section: Environmental Risk Assessmentmentioning

confidence: 99%

Preclinical and Clinical Development of a YFV 17 D-Based Chimeric Vaccine against West Nile Virus

Dayan

Пугачев

Bevilacqua

et al. 2013

Viruses

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Substantial success has been achieved in the development and implementation of West Nile (WN) vaccines for horses; however, no human WN vaccines are approved. This review focuses on the construction, pre-clinical and clinical characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed of a yellow fever (YF) 17D virus in which the prM-E envelope protein genes are replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF 17D in mice and rhesus and cynomolgus monkeys. The vaccine elicited neutralizing antibody titers after inoculation in hamsters and monkeys and protected immunized animals from lethal challenge including intracerebral inoculation of high dose of WN NY99 virus. Safety, viremia and immunogenicity of ChimeriVax-WN02 were assessed in one phase I study and in two phase II clinical trials. No safety signals were detected in the three clinical trials with no remarkable differences in incidence of adverse events (AEs) between vaccine and placebo recipients. Viremia was transient and the mean viremia levels were low. The vaccine elicited strong and durable neutralizing antibody and cytotoxic T cell responses. WN epidemiology impedes a classical licensure pathway; therefore, innovative licensure strategies should be explored.

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Construction and biological characterization of artificial recombinants between a wild type flavivirus (Kunjin) and a live chimeric flavivirus vaccine (ChimeriVax-JE)

Cited by 16 publications

References 44 publications

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

Microarray Techniques for Evaluation of Genetic Stability of Live Viral Vaccines

Preclinical and Clinical Development of a YFV 17 D-Based Chimeric Vaccine against West Nile Virus

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