Development of varicella vaccine in Japan and future prospects.

In Japan, Dr. Michiaki Takahashi (1928-2013) successfully developed the first live attenuated varicella vaccine in the world. The virus used for this vaccine was varicella-zoster virus isolated from the vesicular fluid of a child with typical varicella and it was named the Oka strain after the family name of the child. In 1974, a patient with nephrosis developed varicella in the Pediatric Ward, and uninfected pediatric patients received varicella vaccine immediately. As a result, there were no cases of varicella in the other children and all of the vaccinated children acquired immunity to the disease. These results were published in the Lancet, demonstrating the safety and efficacy of varicella Oka strain vaccine for the first time. When clinical studies were conducted at the start of vaccine development, most of the subjects were pediatric patients with a high risk of contracting severe varicella. Therefore, the development process was different from that for other vaccines, since clinical studies are generally performed in healthy individuals. This vaccine was approved in Japan in 1986, and voluntary single-dose vaccination for children aged 1 year or older was started in 1987. However, the vaccination coverage rate remained low and the number of patients with varicella did not decrease significantly. Due to its voluntary status, the cost of vaccination was borne by the child's family and this was considered to be a reason for the low coverage rate. Moreover, although the vaccine achieved a good antibody response, the number of cases of breakthrough varicella (BV) was relatively high and showed an increasing trend that was also a concern. In order to increase the coverage rate and reduce BV, the Japanese government changed the varicella vaccination policy from voluntary to routine vaccination in October 2014. At the same time, a two-dose schedule was introduced that involved administration of the vaccine twice at an interval of at least 3 months up to the age of 3 years. At present, cases of varicella are only monitored at the pediatric sentinel clinics in Japan. Therefore, we need to establish a system to survey all patients, in order to demonstrate the efficacy of varicella vaccine based on detailed surveillance data. We also need to investigate the optimum timing of the second dose of the vaccine and the necessity for further booster vaccination. A combined live vaccine containing varicella vaccine has not yet been approved in Japan. Because of the greater convenience of combined vaccines, development and introduction of such a vaccine in the future would be desirable. Routine varicella vaccination is also expected to eventually reduce the occurrence of herpes zoster, although there are no supporting epidemiological data. The prevalence of herpes zoster has attracted attention, but it is necessary to develop a surveillance system for this disease. In March 2016, use of varicella vaccine to prevent herpes zoster in adults aged 50 years or older was approved in Japan, and the results of this policy change need to be assessed.