Five-year immunity persistence following immunization with inactivated enterovirus 71 type (EV71) vaccine in healthy children: A further observation

Abstract

The longevity of antibodies induced by inactivated enterovirus 71 type (EV71) vaccine is not well studied. To estimate the immunity persistence following two-dose vaccination of EV71 vaccine, a five-year follow-up study was conducted as an extension of a Phase III clinical trial. In this study, a sub-cohort of volunteers who was eligible for enrollment and randomly administrated either 2 dose EV71 vaccine or placebo in the phase III clinical trial was selected, and then further observed 64 months post the 1st vaccination. 211 Subjects (106 vaccine subjects and 105 placebo subjects) who provided a full series of blood samples (at all the sampling points) were included in the final analyzed population. Seropositive rate (SR) and geometric mean titer (GMT) of the neutralizing antibodies (NAb) was calculated to detect the dynamic profiles of EV71 vaccine-induced immunogenicity. SR at the 5th year remained 94.34% in the vaccine subjects, with a GMT of 141.42. The SR was 71.43% in the placebo subjects, with a GMT of 71.83. Despite natural infection consistently promoted the NAb increase in the placebo subjects, the SR and GMT in vaccine subjects remained significantly higher than that in the placebo subjects at all the sampling points. The inactivated EV71 vaccine-induced immunity had a good persistence, within 5 years following the primary vaccination.

Trial registration: ClinicalTrials.gov NCT03281174.

Keywords: children; immunogenicity; inactivated enterovirus 71 type vaccine; neutralizing antibody; persistence.

Figures

Figure 1.

Dynamic profiles of EV71-NAb seropositive rates during a 5-year follow-up period in healthy children immunized with EV71 vaccine or placebo. Blood samples from 211 participants, who provided a full series of blood samples within the 5-year follow up period were collected to evaluate the production of EV71 NAb. These children were 6–35 months old at the enrollment of the initial study and about 6–8 years at the last observed time point. (a) by the cutoff value of 1:8 (b) by the cutoff value of 1:16 (c) by the cutoff value of 1:32. The bar indicates the 95% confidence interval.

Figure 2.

Dynamic profiles of EV71-NAb GMT during a 5-year follow-up period in healthy children immunized with the EV71 vaccine or placebo. Blood samples from 211 participants, who provided a full series of blood samples within the 5-year follow up period, were collected to evaluate the production of EV71 NAb. These children were 6–35 months old at the enrollment of the initial study and about 6–8 years at the last observed time point. (a) in all the 211 subjects (b) in the EV71-NAb seropositive (NAb≥1:8) subjects. The bar indicates the 95% confidence interval.

Figure 3.

The dynamic profiles of EV71 NAb titer distribution during a 5-year follow up period in healthy children immunized with the EV71 vaccine or placebo. Blood samples from 211 participants, who provided a full series of blood samples within the 5-year follow up period were collected to evaluate the production of EV71 NAb. These children were 6–35 months old at the enrollment of the initial study and about 6–8 years at the last observed time point. (a) month 2 (b) month 8 (c) month 14. (d) month 26. (e) month 64. Reverse distributions were displayed, the y axes indicate the proportion of subjects with a NAb titer no less than a certain titer.

Figure 4.

Definitions of different analysis sets in the initial phase III clinical trial and its follow-up studies. FAS and PPS indicates Full Analysis Set and Per Protocol Set respectively. The dataset marked by the dashed box was the final analyzed set in this study. *During the extended follow-up period in this study (month26-month64), neither herpangina nor extra vaccination was found, and 16 HFMD case (8 in vaccine group and 8 in placebo group) were found through the retrospective survey, but no associated pathogen information was obtained.