A Vaccine to Prevent Enterovirus 71 Infections

Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease and herpangina — both of which involve painful vesicular eruptions, primarily in young children. The infection is usually self-limited and without residual disability. In some cases, however, there is significant central nervous system injury, multisystem disease, and even death. Most of the severe infections have occurred in the Asia–Pacific region, particularly in China, where large outbreaks have been described. Results of two randomized, placebo-controlled, double-blind, phase III trials of cell-culture–based inactivated EV71 subtype C4 vaccines have just been published.

In a manufacturer-sponsored trial conducted at 35 sites in Jiangsu Province, China, Zhu and colleagues randomized 10,077 healthy infants aged 6 to 35 months to receive two intramuscular injections of an alum-adjuvanted EV71 vaccine (developed by Sinovac Biotech) or placebo 4 weeks apart. During a 12-month surveillance period, 0.3% of vaccinees and 2.1% of controls developed EV71-associated disease, diagnosed by polymerase chain reaction (PCR) assay or viral isolation. In the intent-to-treat population, vaccine efficacy was 94.8% against such disease and 100% both in preventing EV71-associated hospitalization and in preventing neurologic complications. Among participants who received two vaccine doses, 98.8% developed protective titers of neutralizing antibodies by day 56. Adverse events were similar between the groups.

In a trial conducted in seven counties of the Guangxi Zhuang Autonomous Region, China, Li and colleagues and colleagues randomized 12,000 healthy children aged 6 to 71 months to receive two intramuscular injections of a different EV71 vaccine (developed by the Institute of Medical Biology, Chinese Academy of Medical Sciences) or placebo with a 4-week interval between doses. In the subgroup tested for immunogenicity, 100% of those who received two doses showed seroconversion at day 56. Over the course of two epidemic seasons, vaccine efficacy against PCR-confirmed EV71-associated hand, foot, and mouth disease was 97.4% in the intent-to-treat population. The only severe cases (2, with 1 death) occurred in placebo recipients. Adverse events were generally mild (e.g., fever, pain at the injection site) and were more common in vaccinees.