HealthDay News — An inactivated vaccine for enterovirus 71 (EV71) was safe and effective in children, results of a large phase 3 study indicate.
Overall, vaccine efficacy was 90% (95% CI: 67.1-96.9) for EV71-associated hand, foot and mouth disease and 80% (95% CI: 58.2%-90.8%) against any EV71 disease, Feng-Cai Zhu, MSc, of the Jiangsu Provincial Center for Disease Control and Prevention in Nanjing, China, and colleagues reported in Lancet.
The randomized double-blind placebo-controlled phase 3 trial, examined the safety, efficacy and immunogenicity of the alum-adjuvanted EV71 vaccine in 10,245 participants aged 6 to 35 months. The researchers randomly assigned 4,907 patients to receive the vaccine and 4,939 to receive placebo.
Serious adverse events occurred in 1.2% of children who received the vaccine vs. 1.5% of those who received placebo.
Since the EV71 was first described in the 1960s, there have been numerous outbreaks, accounting for more than 6 million cases and 2,000 fatalities. Hand, foot and mouth disease, consisting of rashes and blisters on the palms and soles and in the mouth, is the most common course of illness.
Some children experience nonspecific symptoms, including mild fever and respiratory infection, whereas others are asymptomatic. EV71 can also cause severe neurologic problems, such as aseptic meningitis and encephalitis.
Zhu and colleagues conducted the phase 3 study after results from earlier phase 1 and 2 studies suggested the vaccine was safe and immunogenic.
Children were enrolled from more than 500 hospitals and clinics. The vaccine, which contained EV71 genotype C4 and an alum adjuvant, was administered on days zero and 28, and children were observed again at months five, eight, 11 and 14 after vaccination. The researchers vaccinated fewer than 40% of children from each village to ensure that herd immunity would not develop. Active surveillance was performed from day 56 through month 14.
Parents were asked to bring any child with signs or symptoms of illness to the clinic promptly to have throat and rectal swabs and a blood tests performed to test for enteroviruses and other pathogens.
A total of 17,038 illnesses occurred in 7,328 children between March 2012 and March 2013. All confirmed EV71 cases were matched with five healthy controls to compare neutralizing antibody titers at day 56.
Among participants who had been administered the vaccine, there were three confirmed cases of EV71 hand, foot and mouth disease, and eight cases of any EV71-associated illness vs. 30 cases of hand, foot and mouth disease (P=0.0001) and 41 cases of EV71-associated illness (P<0.0001) in the placebo group, the researchers found.
None of the children in the vaccine group were hospitalized vs. eight children with hand, foot and mouth disease in the placebo group, one of whom also had oral herpes and encephalitis. This findings suggested a vaccine efficacy of 100% (95% CI: 41.6-100) for potentially severe or severe cases, the researchers noted.
The most common injection-site reactions were redness, pain and induration. Diarrhea and fever were the most frequent systemic adverse events, the researchers reported.
A total of two children each in both the vaccine and placebo groups died during the study period of unrelated causes. No deaths or serious adverse events were attributable to the vaccine.
“This exploratory analysis on the correlates of immunity is a substantial step forward; however, more evidence of its validity is needed,” the researchers wrote.
In an accompanying editorial, Nigel Crawford, MD, and Steve Graham, MD of the University of Melbourne in Australia noted the low morbidity and mortality associated with EV71.
Study limitations included testing only for EV71, which may have yielded lower vaccine efficacy if children were coinfected with other pathogens, and lack of baseline screening to exclude seropositive children, who would have already been immune to EV71. Another limitation was ot including children aged 6 months and younger, a population in whom EV71 can be particularly severe.
Crawford and Graham called for more studies to assess the vaccine at birth, and ages 2, 3 and 4 months to determine optimal protection.