Abstract
An enterovirus 71 (EV71) vaccine for the prevention of hand, foot, and mouth disease (HMFD) is available, but it is not known whether the EV71 vaccine cross-protects against Coxsackievirus (CV) infection. Furthermore, although an inactivated circulating CVA16 Changchun 024 (CC024) strain vaccine candidate is effective in newborn mice, the CC024 strain causes severe lesions in muscle and lung tissues. Therefore, an effective CV vaccine with improved pathogenic safety is needed. The aim of this study was to evaluate the in vivo safety and in vitro replication capability of a noncirculating CVA16 SHZH05 strain. The replication capacity of circulating CVA16 strains CC024, CC045, CC090 and CC163 and the noncirculating SHZH05 strain was evaluated by cytopathic effect in different cell lines. The replication capacity and pathogenicity of the CC024 and SHZH05 strains were also evaluated in a neonatal mouse model. Histopathological and viral load analyses demonstrated that the SHZH05 strain had an in vitro replication capacity comparable to the four CC strains. The CC024, but not the SHZH05 strain, became distributed in a variety of tissues and caused severe lesions and mortality in neonatal mice. The differences in replication capacity and in vivo pathogenicity of the CC024 and SHZH05 strains may result from differences in the nucleotide and amino acid sequences of viral functional polyproteins P1, P2 and P3. Our findings suggest that the noncirculating SHZH05 strain may be a safer CV vaccine candidate than the CC024 strain.
Highlights
Hand, foot, and mouth disease (HFMD) mainly affects infants and children, and occasionally occurs in adults worldwide
The results demonstrated that the SHZH05 strain and the Changchun 024 (CC024), CC045, CC090, and CC163 strains induced similar cytopathic effect (CPE) in Vero and baby hamster kidney (BHK) cells at 96 h post-infection (Figure 1)
Strain (Figure 4C,F,I) or of mock infected neonatal mice (Figure 4A,D,G). These results demonstrate that the CC024 strain had a strong tropism for muscle and lung tissues and was responsible for the severe lesions in these tissues, but that the SHZH05 strain did not have a muscle tropism or cause any lesions in this neonatal mouse model
Summary
Foot, and mouth disease (HFMD) mainly affects infants and children, and occasionally occurs in adults worldwide. Several major outbreaks have occurred in Southeast Asia in recent decades [1]. CVA16 infections can lead to severe complications, such as aseptic meningitis, encephalitis, lethal myocarditis, and pneumonia [3,4,5,6]. Coinfection with CVA16 and EV71 increases genetic recombination between the two viruses, making control of HFMD epidemics even more complex and difficult [7]. Such a coinfection may have been responsible for an HFMD outbreak in Fuyang, Anhui Province, China in 2008 [1]
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