Short‐Term Safety of Live Attenuated Japanese Encephalitis Vaccine (SA14–14–2): Results of a Randomized Trial with 26,239 Subjects

Abstract

The short-term safety of an effective and inexpensive new live attenuated Japanese encephalitis vaccine (SA14-14-2) was studied in a randomized trial, using block randomization. Of 26,239 children who were enrolled, half received the vaccine and half served as controls. Subjects were prospectively followed for 30 days for severe adverse events, such as encephalitis, meningitis, and ''all-cause'' hospitalization. No cases of encephalitis or meningitis occurred in either group. The upper 95% confidence limit for adverse events not occurring among subjects receiving their first dose was 4.1/ 10,000. Risk ratios and 95% confidence intervals for other adverse events were 0.70 (0.43-1.15) for all-cause hospitalization, 0.91 (0.37-2.22) for seizure, and 0.79 (0.56-1.11) for fever lasting §3 days. These data attest to the short-term safety of the SA14-14-2 virus strain and the hamster kidney cell substrate.Japanese encephalitis (JE) is an important public health probwith a three-dose primary vaccination series recommended and yearly boosters administered in some countries. Thus, the exlem throughout a vast region of Asia. Conservative estimates place the annual incidence at ú35,000 cases, mostly in children pense and inconvenience of mouse brain-derived JE vaccine hinder immunization efforts. Adding to this difficulty has been [1]. Among these, ú10,000 die of JE, and an equal number develop permanent neurologic sequelae. JE is caused by a flathe occurrence of rare hypersensitivity and neurologic reactions, including encephalitis and encephalopathy, that have vivirus that circulates in zoonotic cycles involving many vertebrate species and is transmitted to humans by the bite of several been associated temporally (although not necessarily causally) with the existing vaccine [3]. mosquito species. Because of its zoonotic cycle, prospects for eradicating JE from the environment are dim, and universalIn 1988, an inexpensive (US $.75/dose) live attenuated primary hamster kidney-derived JE vaccine (SA14-14-2) was childhood vaccination is likely to remain essential for its control in the foreseeable future. licensed in China [4]. Prior to licensure, trials conducted in highly endemic areas indicated 95% efficacy after a single dose A killed mouse brain-derived JE vaccine with 91% efficacy (95% confidence interval [CI], 70%-97%) [2] that is manufac- [1,5]. A recent case-control study conducted in an area less endemic for JE showed 80% effectiveness (95% CI, tured by Biken (Osaka, Japan) is available internationally, although in insufficient quantities to meet the need worldwide.44%-93%) after one dose and 97.5% effectiveness (95% CI, 86%-99.6%) after two doses administered 1 year apart [6]. Similar mouse brain-derived vaccines are produced in limited quantities by manufacturers in other countries. The price of Some information concerning the safety of this vaccine is known. Results of a nonexperimental cohort study of the candiJapanese-produced JE vaccine in Asia is about US $5/dose, date vaccine were published in the Chinese li...

Adverse Events Following Live JE Vaccination: An Observational Study

“…This is comparable to the observation of Liu ZL et al [10] where 4.9% in a population of 266 children experienced fever 6.9% of vaccinees from Bellary and 14.7% from Burdwan experienced fever in the first week after vaccination. Xin et al did not come across fever during the 1 st 2 weeks in the 47 children aged 5-6 years who received the vaccine [11].…”

Japanese Encephalitis: Epidemiology and Current Perspectives in Vaccines

“…Since then rigorous studies have shown good safety. A large randomised controlled trial in China with 26,239 subjects (13,266 vaccinated children) showed similar relative risk of adverse events (hospitalisation, seizures, fever) in the vaccinated and unvaccinated groups after 30 days follow up and no severe adverse or neurological events were observed [68]. Two further studies including one in South Korea have shown no severe adverse events and a low rate of mild events-fever, rash, irritability loss of appetite in around 10% [66] 3 .…”

“…So far the vaccine has remained attenuated in animal studies and viraemia induced by vaccination is likely to be below threshold for infection to mosquitos [29]. Furthermore, the vaccine has a good safety and efficacy record in clinical studies (Table 3) [13,[61][62][63][64][65][66][67][68][69][70][71].…”

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

“…It resulted in a significant reduction of JE incidence rate in Japan and Taiwan. 8 Due to the occurrence of a single case of acute disseminated encephalomyelitis temporally associated with JE-VAX prompted the major manufacturer (BIKEN Ò , distributed as JE-VAX by Sanofi Pasteur, Lyon, France) to discontinue production and all remaining doses expired in May 2011. 9 However, MBJEV produced by the Thai Governmental Pharmaceutical Organization (TGPO) is currently available in Thailand, which has been introduced into the National Immunization Program (NIP) since 1990.…”

“…JE-CV is a recombinant vaccine based on a chimeric of JEV and yellow fever virus 17D vaccine strain (YFV17D). 8 The vaccine was constructed by replacing the prM and E-encoding cDNA of yellow fever virus (YFV) with that of the live-attenuated SA14-14-2 strain of JEV. 15,16 It was approved in Australia and Thailand in 2010.…”