Vaccine development against dengue and Japanese encephalitis: report of a World Health Organization meeting

Chambers, Thomas J.; Tsai, Theodore F.; Pervikov, Yuri; Monath, Thomas P.

doi:10.1016/s0264-410x(97)00195-3

Cited by 74 publications

(42 citation statements)

References 6 publications

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“…Recent approaches include the use of inactivated whole-virion vaccines (23), synthetic peptides (5,121,122), subunit vaccines (31,101,140), vector expression, recombinant live vector systems (23,102), infectious cDNA clone-derived vaccines (16,25,79,80,82,93,113), and naked DNA (24,84). The last two approaches appear to be the most promising.…”

Section: Vaccine Developmentmentioning

confidence: 99%

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Dengue and Dengue Hemorrhagic Fever

Gubler¹

1997

Tropical Infectious Diseases

633

756

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Section: Vaccine Developmentmentioning

confidence: 99%

“…The development of naked DNA vaccines is in its infancy but shows great promise (24). This area has been recently reviewed (23,144). Despite the promising progress, it is unlikely that an effective, safe, and economical dengue vaccine will be available in the near future.…”

Section: Vaccine Developmentmentioning

confidence: 99%

Dengue and Dengue Hemorrhagic Fever

Gubler¹

1997

Tropical Infectious Diseases

633

756

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“…The development of a vaccine against DEN is considered a high priority by the World Health Organization. 3 The pathogenesis of DHF drives the design of DEN vaccines. DHF is an immunopathological disease, which occurs primarily in individuals who have sustained a prior infection with one of the DEN serotypes and are exposed to another, heterologous serotype.…”

Section: Introductionmentioning

confidence: 99%

Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All

Guirakhoo

Kitchener²,

Morrison³

et al. 2006

Human Vaccines

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188

136

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A randomized double-blind Phase I Trial was conducted to evaluate safety, tolerability, and immunogenicity of a yellow fever (YF)-dengue 2 (DEN2) chimera (ChimeriVax™-DEN2) in comparison to that of YF vaccine (YF-VAX ® ). Forty-two healthy YF naïve adults randomly received a single dose of either ChimeriVax™-DEN2 (high dose, 5 log plaque forming units [PFU] or low dose, 3 log PFU) or YF-VAX ® by the subcutaneous route (SC). To determine the effect of YF preimmunity on the ChimeriVax TM -DEN2 vaccine, 14 subjects previously vaccinated against YF received a high dose of ChimeriVax™-DEN2 as an open-label vaccine. Most adverse events were similar to YF-VAX ® and of mild to moderate intensity, with no serious side-effects. One hundred percent and 92.3% of YF naïve subjects inoculated with 5.0 and 3.0 log 10 PFU of ChimeriVax TM -DEN2, respectively, seroconverted to wt DEN2 (strain 16681); 92% of subjects inoculated with YF-VAX ® seroconverted to YF 17D virus but none of YF naïve subjects inoculated with ChimeriVax-DEN2 seroconverted to YF 17D virus. Low seroconversion rates to heterologous DEN serotypes 1, 3 and 4 were observed in YF naïve subjects inoculated with either ChimeriVax™-DEN2 or YF-VAX ® . In contrast, 100% of YF immune subjects inoculated with ChimeriVax™-DEN2 seroconverted to all 4 DEN serotypes. Surprisingly, levels of neutralizing antibodies to DEN 1, 2 and 3 viruses in YF immune subjects persisted after 1 year. These data demonstrated that (1) the safety and immunogenicity profile of the ChimeriVax™-DEN2 vaccine is consistent with that of YF-VAX ® , and (2) preimmunity to YF virus does not interfere with ChimeriVax TM -DEN2 immunization, but induces a long lasting and cross neutralizing antibody response to all 4 DEN serotypes. The latter observation can have practical implications toward development of a dengue vaccine.

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“…In addition, molecular biological studies on the JEV genome indicate that expression of the premembrane (prM) and E genes in mammalian cells leads to the production of small, capsidless, noninfectious virus-like particles (VLP) that possess the E antigen (E-VLP), and its conformation-dependent protective epitopes are almost equivalent to those of the authentic E antigen in JEV virions (29-31, 44, 50). Thus, some attempts to develop second-generation JE vaccines have focused on the efficient production of the E-VLP antigen.A recombinant vaccinia virus expressing cDNA encoding the prM and E proteins was a promising JE vaccine candidate; it produced extracellular E-VLP in cell cultures and induced neutralizing antibodies and protective immunity against JEV in vaccinated mice and rabbits (6,26,31,50). Phase I human trials tested with NYVAC-JEV, a recombinant vaccinia virus constructed from an attenuated vaccinia virus strain, or with ALVAC-JEV, based on a canarypox virus vector, however, revealed their low immunogenicity, in particular, lower humoral immune responses in vaccinia-preimmune recipients (26,28,37 …”

mentioning

confidence: 99%

“…Vaccination is the only effective way to prevent flavivirus infection in humans and domestic animals. Inactivated JEV and tick-borne encephalitis virus vaccines and attenuated yellow fever virus vaccine are in widespread production and use, whereas other flavivirus vaccines are under development or in human trials (6,26,37). The only licensed JE vaccine, JE-VAX, which is distributed commercially and available internationally, is formalin-inactivated JEV prepared from a number of JEV-infected mouse brains.…”

mentioning

confidence: 99%

Stable High-Producer Cell Clone Expressing Virus-Like Particles of the Japanese Encephalitis Virus E Protein for a Second-Generation Subunit Vaccine

Kojima

Yasuda

Asanuma

et al. 2003

J Virol

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We produced and characterized a cell clone (J12#26 cells) that stably expresses Japanese encephalitis virus (JEV) cDNA, J12, which encodes the viral signal peptide, premembrane (prM), and envelope (E) proteins (amino acid positions 105 to 794). Rabbit kidney-derived RK13 cells were transfected with a J12 expression plasmid, selected by resistance to marker antibiotics, and cloned by two cycles of a limiting-dilution method in the presence of antibiotics, a procedure that prevents the successful generation of E-producing cell clones. J12#26 cells secreted virus-like particles containing the authentic E antigen (E-VLP) into the culture medium in a huge enzyme-linked immunosorbent assay-equivalent amount (2.5 g per 10 4 cells) to the internationally licensed JE vaccine JE-VAX. E-VLP production was stable after multiple cell passages and persisted over 1 year with 100% expressing cells without detectable cell fusion, apoptosis, or cell death, but was suspended when the cells grew to 100% confluency and contact inhibition occurred. Mice immunized with the purified J12#26 E-antigen without adjuvant developed high titers of neutralizing antibodies for at least 7 months and 100% protection against intraperitoneal challenge with 5 ؋ 10 6 PFU of JEV when examined according to the JE vaccine standardization protocol. These results suggest that the recombinant E-VLP antigen produced by the J12#26 cell clone is an effective, safe, and low-cost second-generation subunit JE vaccine.Japanese encephalitis virus (JEV), a member of the flavivirus family, is the causative agent of Japanese encephalitis (JE), which is a pandemic infectious disease of major public health importance in Asia (9, 48). Vaccination is the only effective way to prevent flavivirus infection in humans and domestic animals. Inactivated JEV and tick-borne encephalitis virus vaccines and attenuated yellow fever virus vaccine are in widespread production and use, whereas other flavivirus vaccines are under development or in human trials (6,26,37). The only licensed JE vaccine, JE-VAX, which is distributed commercially and available internationally, is formalin-inactivated JEV prepared from a number of JEV-infected mouse brains. The brain-derived whole virion vaccine is costly to manufacture and carries potential risks of allergic reactions to brain basic proteins or contamination by mouse prion proteins, and there are biosafety issues of manufacturing an infectious pathogen. Thus, the development of second-generation JE vaccines that are not derived from the brain, do not involve infectious JEV, and are of low cost is a top priority.The 53-kDa envelope (E) glycoprotein of JEV has an important role in virus adhesion and entry into target cells through receptor binding (20,34) and, therefore, in inducing neutralizing antibodies that protect hosts against JEV infection (8,24,32,36). The protective epitopes on the E antigen are suggested to be formed in highly conformational structures of JEV virions (20, 34) based on antigenic analyses with panels of monoclonal ant...

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Vaccine development against dengue and Japanese encephalitis: report of a World Health Organization meeting

Cited by 74 publications

References 6 publications

Dengue and Dengue Hemorrhagic Fever

Dengue and Dengue Hemorrhagic Fever

Live Attenuated Chimeric Yellow Fever Dengue Type 2 (ChimeriVax™-DEN2) Vaccine: Phase I Clinical Trial for Safety and Immunogenicity: Effect of Yellow Fever Pre-immunity in Induction of Cross Neutralizing Antibody Responses to All

Stable High-Producer Cell Clone Expressing Virus-Like Particles of the Japanese Encephalitis Virus E Protein for a Second-Generation Subunit Vaccine

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