A 5‐year molecular epidemiology survey of human enterovirus 71 before vaccine application in Yunnan Province, China

Abstract

Enterovirus A71 (EV‐A71) infection is known to cause hand, foot, and mouth disease (HFMD). Last year, an inactivated EV‐A71 whole virus vaccine was used to prevent this disease in Yunnan, China. To obtain a viral genetic background for evaluating vaccine protection and monitor the adaptive evolution of the virus after the vaccination, a 5‐year molecular epidemiology survey was performed before the vaccination. Twenty‐six EV‐A71 strains were separated from 561 stool specimens of patients with serious HFMD. The whole‐genomic sequences of these strains were sequenced. Phylogenetic trees were constructed, and the mutation spectra were analyzed based on these viral sequences. There was no obvious mutation for the circular EV‐A71 strains of the same year. Pathogenic EV‐A71 strains may arise from a “subgroup” randomly each year. Whole‐genomic analyses showed that a hotspot nonsynonymous substitution potentially affecting the immunogenicity of vaccines was found in the 2A gene, but not in genes of the viral capsid proteins, and the genetic diversity of whole viral genomes associated with the incidence of HFMD. Therefore, it will be valuable to monitor the genome‐wide changes of EV‐A71 to detect the adaptive mutations affecting immunogenicity or perform investigations using genetic diversity as a parameter.

Isolation and characterization of a novel clade of coxsackievirus B2 associated with hand, foot, and mouth disease in Southwest China

“…Sequence alignment and phylogenetic analyses were conducted using MEGA 7.0 software 22 . On the basis of entire VP1 sequences of CVB2 available in GenBank and one sequence in this study, the phylogeny of CVB2 was constructed.…”

“…Sequence alignment and phylogenetic analyses were conducted using MEGA 7.0 software. 22 On the basis of entire VP1 sequences of CVB2 available in GenBank and one sequence in this study, the phylogeny of CVB2 was constructed. In the phylogenetic tree, some sequences with the same country and temporal origin that were closely related were removed to obtain a simple and clear phylogenetic tree.…”

The Immungenicity and Cross-Neutralizing Activity of Enterovirus 71 Vaccine Candidate Strains

“…In 2004-2005, C4 replaced the B4 sub-genotype as the main genotype in Taiwan [10]. In mainland China, C4 has remained the predominant subgenotype since its first isolation in 1997 [3,11,12].…”