Current status of global use of Japanese encephalitis vaccine

Japanese encephalitis (Japanese encephalitis,JE, Japanese encephalitis for short), also known as Japanese encephalitis, commonly known as "encephalitis", is a natural focus disease caused by Japanese encephalitis virus. It is transmitted by mosquito vectors and distributed in Asia. It is popular in summer and autumn. Japanese encephalitis mostly has an acute onset, which often manifests as sudden high fever, chills, headache, myalgia, angular arch reflex, mental confusion, acute flaccid paralysis can occur, and about 75% of children have convulsion symptoms. The disease can rapidly develop into severe encephalitis with mental disorders, systemic or focal neurological abnormalities, gradual decline in consciousness or even coma, severe patients often need to use a ventilator, about 30% of severe patients have residual sequelae, and the mortality rate is about 20% ~ 30%. At present, about 3.4 billion people in the world are in the epidemic area of Japanese encephalitis. Due to its high mortality and disability rate, Japanese encephalitis is an important public health problem in the world, especially in Southeast Asia and Western Pacific.

JE virus is mainly transmitted by Culex mosquitoes, and there is an animal cycle in proliferating hosts such as pigs and birds. Culex tritaeniorhynchus is the most important vector, which breeds in ponds and rice fields and bites mainly at night. Due to the presence of an animal host, JE virus cannot be eliminated, but universal vaccination of humans in endemic areas can potentially control JE.

According to the World Health Organization (WHO) position paper on Japanese encephalitis vaccine (2016), there are about 15 kinds of Japanese encephalitis vaccine based on type 3 JEV in various countries in the world, which can be classified into 4 categories, including inactivated Japanese encephalitis vaccine (mouse brain tissue), inactivated Japanese encephalitis vaccine (Vero cell), live attenuated Japanese encephalitis vaccine (hamster kidney cell) and live attenuated Japanese encephalitis vaccine (recombinant chimeric), among them, the vaccine of mouse brain tissue culture is recommended by WHO to be replaced by other kinds of vaccine due to safety problems. Europe, North America, Japan and other countries and regions mainly approved and used inactivated Japanese encephalitis vaccine (Vero cells).

Japan and South Korea, as developed countries with high-risk epidemic areas of Japanese encephalitis, have accumulated rich experience in the process of prevention and control. Japan first discovered cases of Japanese encephalitis in 1871. In 1956, Japan incorporated mouse brain tissue Japanese encephalitis vaccine (JE-MB)(Nakayama strain) into its children's immunization program. Later, it was found that JE-MB could cause characteristic delayed allergic reactions (0.8-6.3/100000 doses), etc. Therefore, it was improved to safer Vero cell cultured inactivated vaccine (JE-VC)(Beijing-1 strain) in 2010. South Korea and Japan have made similar progress. In 2000, a 5-dose JE-MB immunization strategy was adopted: 3-dose basic immunization (1-2 years old) and 2-dose booster immunization (6-13 years old). After being approved for marketing by the Korea Food and Drug Administration in JE-CV 2015, it gradually began to spread with the advantage of 2 doses (≥ 1 year old, 1-2 years apart).

Europe and North America belong to the low-risk or non-epidemic areas of Japanese encephalitis, so the United States, Britain, Northern Europe and other developed countries in Europe and the United States have not included Japanese encephalitis vaccine into the immunization program. Only tourists or long-term residents in Japanese encephalitis epidemic areas are recommended to be vaccinated with inactivated Japanese encephalitis vaccine (JE-VC) or recombinant chimeric vaccine (JE-CV). The vaccination procedure varies with the age and risk of basic immunization, strengthen the immune 1~2 needle.

China, Japan, South Korea, Cambodia, Laos, Myanmar, Nepal, Sri Lanka, Thailand and Vietnam have all launched national vaccination against Japanese encephalitis. The inoculation scheme is shown in the table below.

At present, there are two kinds of Japanese encephalitis vaccine used in China:

One is a live attenuated Japanese encephalitis vaccine (JE-L) based on primary hamster kidney cell culture, which was launched in 1988. The immunization procedure is to vaccinate one dose at the age of 8 months and one dose at the age of 2 years. The other is Vero cell culture-based inactivated Japanese encephalitis vaccine (JE-I) approved and marketed in 2008. Its immunization procedure is to vaccinate two doses at the age of 8 months (with an interval of 7-10 days) and one dose at the age of 2 and 6 years.

The inactivated Japanese encephalitis vaccine and the live attenuated Japanese encephalitis vaccine are the Japanese encephalitis vaccines recommended by the state. Some physical conditions are not suitable for the use of live vaccines available inactivated vaccines. China's existing Japanese encephalitis inactivated vaccine production process does not add antibiotics, formaldehyde, gelatin, preservatives, the first Japanese encephalitis vaccine liquid dosage form does not add preservatives, the safety indicators are up to or better than the pharmacopoeia standard, the product quality reaches the "international advanced, domestic leading" level, is a new generation of pure and safe Japanese encephalitis inactivated vaccine, can be applied to antibiotic allergy, immune deficiency, immune function is low or receiving immune suppression treatment of the special population, the applicable population is more extensive.

1. Deng Xuan, et al. Research progress on sequential immunization of live attenuated Japanese encephalitis vaccine and inactivated Japanese encephalitis vaccine [J]. Chin J Preventive Medicine, 2022,56(5):554-560.

2. World Health Organization position paper on epidemic encephalitis B

3. National Health Commission. "National Immunization Procedures and Instructions for Children with Immunization Regulations and Vaccines (2021 Edition)"