Huang L, Liu X, Li J L, Chang J L, Liu G C, Yu X F, Zhang W Y
Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
Braz J Med Biol Res. 2015 May;48(5):420-6. doi: 10.1590/1414-431X20144298. Epub 2015 Mar 27.
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.
一种用于预防手足口病（HMFD）的肠道病毒71型（EV71）疫苗已上市，但尚不清楚EV71疫苗是否能交叉预防柯萨奇病毒（CV）感染。此外，尽管一种灭活的流行CVA16长春024（CC024）株候选疫苗在新生小鼠中有效，但CC024株会在肌肉和肺组织中引起严重病变。因此，需要一种致病性安全性更高的有效CV疫苗。本研究的目的是评估非流行CVA16 SHZH05株在体内的安全性和体外复制能力。通过不同细胞系中的细胞病变效应评估了流行CVA16株CC024、CC045、CC090和CC163以及非流行SHZH05株的复制能力。还在新生小鼠模型中评估了CC024和SHZH05株的复制能力和致病性。组织病理学和病毒载量分析表明，SHZH05株的体外复制能力与四种CC株相当。CC024株而非SHZH05株分布于多种组织中，并在新生小鼠中引起严重病变和死亡。CC024和SHZH05株在复制能力和体内致病性方面的差异可能源于病毒功能性多聚蛋白P1、P2和P3的核苷酸和氨基酸序列差异。我们的研究结果表明，非流行SHZH05株可能是一种比CC024株更安全的CV疫苗候选株。
