Research progress on sequential immunization of two kinds of Japanese encephalitis vaccines

Japanese encephalitis (Japanese encephalitis,JE, referred to as Japanese encephalitis) is an acute natural foci disease transmitted by Japanese encephalitis virus (Japanese encephalitis virus,JEV) by mosquito vectors (mainly Culex trinaeniorhynchus in China), which mainly invades the central nervous system. It is the main cause of viral encephalitis in children in Asia. 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.

At present, there is no specific treatment for Japanese encephalitis virus, and vaccination is the main measure to prevent and control Japanese encephalitis. There are two kinds of Japanese encephalitis vaccines currently used in China, live attenuated Japanese encephalitis vaccine (JE-L) and inactivated Japanese encephalitis vaccine (JE-I). Due to objective reasons such as the recipient's own health status (such as vaccine adverse reactions, individual immune insufficiency) and subjective choice willingness, as well as vaccine supply and other factors, some subjects who have been vaccinated before but have not completed the whole course of one type of JE vaccine need to use another type of JE vaccine for sequential vaccination, I .e. different varieties or dosage forms of JE vaccine are used alternately.

Therefore, a series of studies on immunogenicity and safety evaluation of sequential vaccination of Japanese encephalitis vaccine have been carried out in China:

There are 4 domestic literatures on the sequential vaccination of Japanese encephalitis vaccine. Three of the literatures contributed important evidence to the safety evaluation, and it was clear that different Japanese encephalitis vaccine sequential vaccination had good safety. Two of the studies showed that the sequential group and the control group had good immunogenicity, and the antibody positive rate reached more than 95% (95.03-100) at 1 month after booster immunization, and the difference between the groups was not statistically significant.

Studies on immunization strategies for the sequential use of different Japanese encephalitis vaccines have also been conducted abroad:

Note: JE‑MB:Inactivated mouse brain‑derived JE vaccine, inactivated Japanese encephalitis vaccine based on rat brain tissue;

JE-VC: Vero cell-Inactivated derived JE vaccine, Vero cell-based inactivated JE vaccine;

JE-L:Live attenuated JE vaccine, live attenuated Japanese encephalitis vaccine;

JE-CV:Live attenuated chimeric JE vaccine, recombinant (chimeric) live attenuated Japanese encephalitis vaccine.

In terms of safety, different studies have shown that the adverse reactions caused by sequential immunization strategy are mainly mild to moderate reactions, which generally occur within 7 days after vaccination, and can be cured or alleviated for up to 3 days. Local adverse reactions were mainly redness and pain at the injection site (4%~ 57.7%), and systemic adverse reactions were mainly fever (8%~ 39.1%). In terms of immunogenicity, the level of neutralizing antibodies induced by different sequential immunization strategies of Japanese encephalitis vaccine was higher (GMT:398~9144) after 4 weeks of booster immunization. Although the positive conversion rate of some strategies was lower (40.8~53.7), the positive rate after booster immunization could reach more than 90%.

Summary of domestic and foreign Japanese encephalitis vaccine sequential inoculation has the following several situations: inactivated attenuated, attenuated inactivated, but also inactivated, attenuated attenuated. Although there are few studies on the immunogenicity and safety evaluation of different Japanese encephalitis vaccines at home and abroad, and the sample size is small, all studies show good safety and immunogenicity.

In principle, vaccination should follow the same type of vaccine from the same manufacturer to complete the whole vaccination. With the improvement of our society's informed consent and highly autonomous selection requirements for the vaccination process, the grass-roots practice often encounters the phenomenon that guardians choose different types of Japanese encephalitis vaccines for sequential vaccination due to various reasons (such as vaccine adverse reactions, individual immune insufficiency, conformity consciousness, epidemic season, short-term out of stock due to insufficient vaccine supply, etc.),Therefore, grass-roots practice is often faced with the need to consider sequential vaccination,Therefore, the research evidence at home and abroad was collected, and the current status of the use of JE vaccine and the research progress of sequential vaccination were combed to provide reference for JE vaccination.

References:

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.