JAPANESE ENCHEPHALITIS VACCINES - Immunization
 
JAPANESE ENCHEPHALITIS VACCINES
Last Updated : 3/25/2016
Sayenna Uduman*, M I Sahadulla**, Raja Lakshmi***
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JE Vaccine Prevention:
There is little evidence to support a reduction in JE disease burden from interventions other than the vaccination of humans. WHO recommends strong JE prevention and control activities, including immunization in all regions where the disease is a recognized public health priority. Even if the number of JE-confirmed cases is low, vaccination should be considered where there is a suitable environment for JE virus transmission.
An ideal vaccine should be safe, cheap and easy to administer and should generate neutralizing antibodies capable of protecting against JE virus infection. There are 4 main types of JE vaccines currently in use: inactivated mouse brain-derived vaccines, inactivated Vero cell-derived vaccines, live attenuated vaccines, and recombinant vaccines.
The IAP Advisory Committee on Vaccines and Immunization Practices (ACVIP, 2013) recommends considering JE Vaccine for high-risk children under special circumstances indicating JE is a major pediatric health problem, in India.
The CDC recommends vaccine for travelers who plan to spend a month or longer in areas with endemic infection during the virus transmission season. The risk of infection for most travelers to Asia is low but varies on the basis of destination, duration, season, and activities. For some travelers who will be in high-risk settings, vaccination can further reduce the risk for infection. Information on the location of JE virus transmission and detailed information on vaccine recommendations and adverse events can be obtained from the CDC (wwwnc.cdc.gov/travel/).
• Only one JE vaccine is available commercially for use in the United States. An inactivated Vero cell culture-derived vaccine (IXIARO [JE-VC], distributed in the US by Novartis Vaccines and Diagnostics Inc., Cambridge, MA) is licensed for people 2 months of age or older in a 2-dose administered 28 days apart as primary vaccination series.
• Children 2 months through 24 months of age receive 0.25 ml. Adults and children beyond 2 years of age receive 0.5ml. Adults may require a booster dose at 1 year or longer after the primary dose vaccination and before travelling to potential JE virus exposure.
• No efficacy data exist for JE-VC. No safety concerns have been identified
• The vaccine confers no herd immunity because humans are not the primary hosts.
Several groups of vaccines are available currently, in India. The formalin-inactivated vaccines have been safe and effective against JE virus for at least 30 years. Of these, the most widely produced and internationally distributed is the mouse-brain derived inactivated vaccine. The efficacy and the strain from which these are produced are given in Table 1.

Table 1 - Vaccines that are in use against Japanese encephalitis.
Vaccine type JE virus strain Comments
Inactivated    
1. Inactivated mouse brain
Hamster kidney cells derived
Vero-cell culture derived formalin inactivated
Nakayama and Beijing-1, grown in suckling mouse brain
based on the Beijing-3 strain
using P20778 (Indian isolate)
WHO approved vaccine; a seroconversion rate of 80 to 90% with an efficacy rate of 91%.
Has relatively fewer side effects and is easy to manufacture. In an extensive randomized field trial in China, its efficacy was found to range between 76% and 90%.
Has induced high titers of neutralizing antibodies in mice after two injections.
Attenuated    
Live attenuated primary hamster kidney cells SA 14-14-2 In large-scale case–control studies in China has shown >90% protection after two doses with an interval of one year. The IAP ACVIP reviewed the performance of SA-14-14-2 JE vaccine in India since its launch in 2006. According to a recent case control study this vaccine efficacy has been around 60% in Uttar Pradesh and around 70% in Assam.


Formalin Inactivated mouse brain vaccine; have been in use over many years. Children required 3 primary doses followed by booster dose annually. Lasting immunity and adverse allergic reactions are the major concern and that has led to the development of newer and improved vaccines.

Hamster kidney cell-culture-derived inactivated vaccine: This vaccine is based on the Beijing-3 strain of JEV and has been in use in China since 1967 with a clinical efficacy rate ranged between 76% and 90%. Recently, vero-cell culture derived formaldehyde inactivated vaccine using P20778 (Indian isolate) have produced high titers of anti-JEV antibodies in animal models and these findings needed further confirmation in clinical trials.

In recent years a Vero cell-derived purified inactivated JE vaccine–JENVAC, is the first vaccine to be manufactured in the public-private partnership mode between the Indian Council of Medical Research and Bharat Biotech. The clinical trials, showed superior safety and immunogenicity, in comparison to live attenuated vaccine The most significant benefit of the JENVAC is that it can be administered during an epidemic as it is a highly purified and inactivated vaccine. A phase III clinical trials showed 98.7 per cent sero-protection 28 days after the first dose and 99.8 per cent sero-protection 28 days after the second dose.

Live attenuated vaccine based on cell culture based: Studies on the 2-dose administration of attenuated vaccine in the primary immunization schedule appeared to be highly immunogenic and safe. A case control study in Nepal had shown an efficacy rate of 98% with a single vaccine dose administration and the long term efficacy of this observation is required. .

Other JE vaccines that include a live, attenuated “chimeric” vaccine which uses a yellow fever vaccine virus strain as its backbone (ChimeriVax-JE, manufactured by Acambis); a recombinant protein based vaccines, and DNA vaccines. These vaccines have better immunogenicity and lesser vaccine adverse reactions.

Conclusions:
Approved vaccines are available to prevent serious encephalitis infection for children 2 months of age and older JE vaccine is recommended for travelers to Asia who plan to spend at least a month in areas where infection is highly prevalent WHO recommends that JE vaccination be integrated into national immunization schedules in areas where the encephalitis disease is recognized as a major public health concern. Apart from mosquito bite control, JE disease control may be possible by a well-planned immunization policies supported by regional disease surveillance system, especially for India.

References

Contributor Information and Disclosures

Sayenna Uduman*, M I Sahadulla**, Raja Lakshmi***
*MD, FAAP Visiting Professor, Infection Control Committee & ID Division of the KIMS
Thiruvananthapuram, Kerala, India

**CMD, ID Division- KIMS.
***Consultant ID, ICC Chair – KIMS


First Created : 3/25/2016

References

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