Global Vaccine Safety

Safety of SA 14-14-2 Japanese encephalitis (JE) vaccine

Extract from report of GACVS meeting of 9-10 June 2005, published in the WHO Weekly Epidemiological Record on 15 July 2005

GACVS considered recent data on the safety profile of live attenuated SA 14-14-2 JE vaccine, provided in a number of expert presentations to the Committee. Live attenuated SA 14-14-2 JE vaccine constitutes more than 50% of the global production of all JE vaccines. The anticipated global demand for JE vaccine in 2012 is expected to exceed the present requirement twofold. Even though several new vaccine candidates are in development, their production and distribution remain uncertain for the time being.

The current production of live attenuated SA 14-14-2 vaccine exceeds 50 million doses annually, most of which are used in China. Neuroattenuation of the virulent JE SA 14-14-2 strain is reported to be based on 57 nucleotide changes and 24 amino acid substitutions, suggesting that reversion to neurovirulence of the vaccine strain would be highly unlikely. Vaccine production is in accordance with WHO technical specifications, including detailed screening for adventitious viruses. Data reported from several studies have shown vaccine efficacy to be between 80% and 99% following single-dose vaccination and 98% or greater with 2 doses of the vaccine. In a comparative observational study of approximately 26 000 subjects in China undergoing routine immunization with JE vaccine, the most common reactions were fever, rash and vomiting. There was no increased risk of serious adverse events within 30 days of vaccination. Data presented to GACVS, covering a 20-year period from 1979 to 1998, contained no reported cases of vaccine-associated JE. Preliminary data on co-administration of the SA-14-14-2 JE vaccine with measles vaccine have been reassuring.

Information is available from both passive and active post-marketing surveillance in the Republic of Korea, where the SA 14-14-2 vaccine was first licensed in 2001. Of 522 vaccinated children actively monitored for adverse events for 4 weeks after vaccination, approximately 10% developed fever higher than 38 °C and a cough. Redness and swelling at the site of injection were observed in less than 1%. These findings are consistent with those reported from China.

GACVS took note of the work of the Program for Appropriate Technology in Health (PATH) – Japanese Encephalitis Project (JE Project), conducted in collaboration with WHO and other partners, in accelerating availability of a safe, effective and affordable JE vaccine in endemic countries in Asia. The SA 14-14-2 vaccine is especially important in this regard. GACVS noted that studies planned in collaboration with the PATH JE Project aim at addressing short- and long-term efficacy and safety, with special reference to co-administration with measles vaccine and evaluating the degree of viraemia in vaccinees.

GACVS acknowledged the excellent safety and efficacy profile of the SA 14-14-2 vaccine but nonetheless recommended more detailed study of the following: the safety profile in special risk groups including immunocompromised people and pregnant women; whether viral shedding occurs in vaccinees and the potential implications of such shedding; further analysis of sequential or co-administration of JE and measles vaccines; the interchangeability of inactivated and live JE vaccines; the safety of vaccine administration to infants aged under 1 year; and the implications for the efficacy and safety of the vaccine in infants with maternal antibodies against JE virus.