Immunogenicity and safety of currently available Japanese encephalitis vaccines: A systematic review

Li, Xing; Ma, Shujuan; Xie, Li; Jiang, Lina; Zhou, Junhua; Xiong, Yiquan; Ding, Hong; Chen, Qing

doi:10.4161/21645515.2014.980197

Cited by 37 publications

(30 citation statements)

References 58 publications

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“…Since, the Aedes aegypti mosquito, the main YFV vector, is omnipresent in (sub)tropical Asia, YFV spill over to Asia and the establishment of epidemics involving urban transmission becomes increasingly realistic (8, 9). For JEV, two licensed vaccines are available, namely Ixiaro ® (inactivated vaccine) and JE-CVax (Imojev ® : YFV-17D-based chimeric live-attenuated vaccine; c-LAV) (10, 11). Another YFV-17D-based tetravalent c-LAV, namely against dengue (CYD-TDV, Dengvaxia ® ) has reached marketing licensure and is being introduced in some countries/regions.…”

mentioning

confidence: 99%

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

Mishra

Boudewijns

Schmid

et al. 2019

Preprint

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ABSTRACTRecent massive outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being not prepared against future YFV epidemics. Here we report that a live-attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev® that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific non-neutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV non-structural (NS) proteins. Our findings reveal the importance of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev® can confer protection against two flaviviruses. This dual protection has implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev® may already be protected against YFV should outbreaks ever occur on that continent as feared by WHO.IMPORTANCEEfficient and safe vaccines exist against yellow fever (e.g. YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses. However, vaccine supply cannot cope with an increasing demand posed by massive urban outbreaks in recent years. Here we report that JE-CVax/Imojev®, a YFV-17D-based chimeric Japanese encephalitis vaccine also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev® may be considered. Moreover, wider use of JE-CVax/Imojev® in Asia may lower the risk of the much-feared YFV spill over to the continent. More in general chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses can be considered dual vaccines, for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection [inherent to current dengue vaccines and dengue vaccine candidates] could be designed.

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mentioning

confidence: 99%

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

Mishra

Boudewijns

Schmid

et al. 2019

Preprint

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“…Commercially available JEV vaccines include a formalin‐inactivated vaccine produced in mouse brain and a live‐attenuated vaccine, SA14‐14‐2, produced in primary hamster kidney cell cultures, both of which perform efficiently . A JEV vaccine very recently approved by the Food and Drug Administration is produced in Vero cells, purified from virus‐infected cell supernatants and inactivated by formalin . JEV vaccines fall into four classes: inactivated mouse brain‐derived, inactivated cell culture‐derived, live‐attenuated and live recombinant (chimeric) vaccines .…”

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confidence: 99%

“…and a live-attenuated vaccine, SA14-14-2, produced in primary hamster kidney cell cultures, both of which perform efficiently (3). A JEV vaccine very recently approved by the Food and Drug Administration is produced in Vero cells, purified from virus-infected cell supernatants and inactivated by formalin (3).…”

mentioning

confidence: 99%

Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice

Lee

Kim

Lee

et al. 2016

Microbiology and Immunology

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The Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis. Although there are four classes of vaccines against JEV, all of them are administered by s.c or i.m injection. Here, the effectiveness of sublingual (s.l.) administration of a JEV live-attenuated vaccine or recombinant modified vaccinia virus Ankara (MVA) vaccine, including JEV prM/E, was investigated. The mice were immunized three times i.m. or s.c. One week after the final immunization by both s.l. and i.m. routes, the titers of IgG1 induced by the recombinant MVA vaccine were higher than those induced by the live-attenuated vaccine, whereas the titers of IgG2a induced by the live-attenuated vaccine were higher than those induced by the recombinant MVA vaccine. However, both vaccines induced neutralizing antibodies when given by either s.l. or i.m. routes, indicating that both vaccines induce appropriate Th1 and Th2 cell responses through the s.l. and i.m. routes. Moreover, both vaccines protected against induction of proinflammatory cytokines and focal spleen white pulp hyperplasia after viral challenge. Virus-specific IFN-γ CD4 and CD8 T cells appeared to increase in mice immunized via both s.l. and i.m. routes. Interestingly, virus-specific IL-17 CD4 T cells increased significantly only in the mice immunized via the s.l. route; however, the increased IL-17 did not affect pathogenicity after viral challenge. These results suggest that s.l. immunization may be as useful as i.m. injection for induction of protective immune responses against JEV by both live-attenuated and recombinant MVA vaccines.

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“…23 It is important to note that the rates of AEs reported with LAJEV are comparable to those reported with other JE vaccines. 42,43 A recent review quantifying the benefits of LAJEV vaccination concluded that since the inclusion of LAJEV in the national Chinese immunization program that provides all immunizations at no cost, the nationwide JE incidence has declined considerably and yielded significant economic and social benefits. 44 In 2001, South Korea was the first country outside of China to license LAJEV and since then, its national regulatory agency has conducted PMS studies 22 and concluded that LAJEV has an acceptable safety profile.…”

Section: Discussionmentioning

confidence: 99%

Use of the live attenuated Japanese Encephalitis vaccine SA 14–14–2 in children: A review of safety and tolerability studies

Ginsburg

Meghani

Halstead

et al. 2017

Human Vaccines & Immunotherapeutics

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Japanese encephalitis (JE) is the leading cause of viral neurological disease and disability in Asia. Some 50-80% of children with clinical JE die or have long-term neurologic sequelae. Since there is no cure, human vaccination is the only effective long-term control measure, and the World Health Organization recommends that at-risk populations receive a safe and effective vaccine. Four different types of JE vaccines are currently available: inactivated mouse brain-derived vaccines, inactivated Vero cell vaccines, live attenuated SA 14-14-2 vaccines and a live recombinant (chimeric) vaccine. With the rapidly increasing demand for and availability and use of JE vaccines, countries face an important decision in theselection of a JE vaccine. This article provides a comprehensive review of the available safety literature for the live attenuated SA 14-14-2 JE vaccine (LAJEV), the most widely used new generation JE vaccine. With well-established effectiveness data, a single dose of LAJEV protects against clinical JE disease for at least 5 years, providing a long duration of protection compared with inactivated mouse brain-derived vaccines. Since 1988, about 700 million doses of the LAJEV have been distributed globally. Our review found that LAJEV is well tolerated across a wide age range and can safely be given to children as young as 8 months of age. While serious adverse events attributable to LAJEV have been reported, independent experts have not found sufficient evidence for causality based on the available data.

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Immunogenicity and safety of currently available Japanese encephalitis vaccines: A systematic review

Cited by 37 publications

References 58 publications

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

A chimeric Japanese encephalitis vaccine protects against lethal yellow fever virus infection without inducing neutralizing antibodies

Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice

Use of the live attenuated Japanese Encephalitis vaccine SA 14–14–2 in children: A review of safety and tolerability studies

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