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Screening of a new candidate coxsackievirus B1 vaccine strain based on its biological characteristics.

ABSTRACT: Coxsackievirus B1 (CVB1) is one of the significant pathogens causing viral myocarditis, hand, foot, and mouth disease (HFMD), and aseptic meningitis, and it has been associated with type 1 diabetes (T1DM). No effective antiviral drugs against CVB1 infection or preventive vaccines are available. Due to the success of two inactivated vaccines against enterovirus 71 and poliovirus, an inactivated Vero cell-based CVB1 vaccine could be developed. In this study, we isolated a high-growth CVB1 virus strain KM7 in Vero cells and developed a Vero-adapted vaccine candidate strain KM7-X29 via three rounds of plaque purification and serial passages. The KM7-X29 strain was grouped into the GII sub-genotype, which belonged to the Chinese epidemic strain and grew to a titer of more than 10⁷ CCID50/ml in Vero cells. The inactivated CVB1 vaccine produced by the KM7-X29 strain induced an effective neutralizing antibody response in BALB/c mice, and maternal antibodies were able to provide a 100% protective effect against lethal challenges with a CVB1 strain in suckling BALB/c mice. Thus, the KM7-X29 strain might be used as a new candidate coxsackievirus B1 vaccine strain. The neonatal murine model of CVB1 infection will contribute to the development of the CVB1 vaccine.

SUBMITTER: Zhang M

PROVIDER: S-EPMC10369069 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Screening of a new candidate coxsackievirus B1 vaccine strain based on its biological characteristics.

Zhang Ming M Xu Danhan D Liu Yuhan Y Wang Xiaohui X Xu Lilan L Gao Na N Feng Changzeng C Guo Wei W Ma Shaohui S

Frontiers in microbiology 20230712

Coxsackievirus B1 (CVB1) is one of the significant pathogens causing viral myocarditis, hand, foot, and mouth disease (HFMD), and aseptic meningitis, and it has been associated with type 1 diabetes (T1DM). No effective antiviral drugs against CVB1 infection or preventive vaccines are available. Due to the success of two inactivated vaccines against enterovirus 71 and poliovirus, an inactivated Vero cell-based CVB1 vaccine could be developed. In this study, we isolated a high-growth CVB1 virus st ...[more]

PMID: 37502400

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Project description:BackgroundEnterovirus A (EV-A), such as enterovirus A71 (EV-A71), generally causes hand, foot, and mouth disease (HFMD). However, limited studies focused on uncommon enterovirus serotypes such as coxsackievirus A12 (CV-A12). This study aimed to provide evidence to determine the molecular characteristics of a CV-A12 strain isolated in Zhejiang province, China.MethodsIn routine surveillance of HFMD, we identified a child case with CV-A12 infection in 2019 in Zhejiang province, China. Enterovirus was examined by using real-time reverse transcription-PCR (qRT-PCR). A partial VP1 sequence was amplified to determine the serotype, and then a full-length CV-A12 genome was sequenced. Nucleotide and amino acid similarity was calculated with those CV-A12 strains available in GenBank. Recombination was detected using RDP 4 and SimPlot. Furthermore, phylogenetic analysis was conducted by using BEAST 1.10, and protein modeling was performed with I-TASSER webserver.ResultsA full-length CV-A12 genome PJ201984 was isolated in a Chinese child with HFMD. The similarities with complete coding sequences of the CV-A12 strains in GenBank ranged between 79.3-100% (nucleotide) and 94.4-100% (amino acid), whereas it was 88.7-100.0% (nucleotide) and 97.2-100% (amino acid) when excluding the CV-A12 prototype strain Texas-12. In PJ201984, amino acid variations were more divergent in P2 and P3 regions than those in P1; the majority of those variations in VP1 (13/15) and VP4 (7/8) were similar to those documented in recently isolated CV-A12 strains in China. Furthermore, recombination was identified in P2 region, which involved a CV-A5 strain collected in China. Phylogenetic analysis revealed that PJ201984 clustered together with multiple CV-A12 strains isolated in China and the Netherlands during 2013-2018, as compared to another cluster consisting of CV-A12 strains in China and France during 2009-2015. Additionally, protein models of VP1 and VP4 in PJ201984 were well predicted to be similar to VP1 protein of EV-A71 and VP4 protein of coxsackievirus A21, respectively.ConclusionsThe full-length CV-A12 genome was characterized to have common recombination in P2 region and be phylogenetically related to those CV-A12 strains isolated in recent years, suggesting a continual spread in China. It warrants strengthening the routine surveillance for uncommon enterovirus serotypes, particularly on possible recombination and variation.

Project description:Feline calicivirus (FCV) is one of the most important pathogens causing upper respiratory tract diseases in cats, posing a serious health threat to these animals. At present, FCV is mainly prevented through vaccination, but the protective efficacy of vaccines in China is limited. In this study, based on the differences in capsid proteins of isolates from different regions in China, as reported in our previous studies, seven representative FCV epidemic strains were selected and tested for their viral titers, virulence, immunogenicity, and extensive cross-protection. Subsequently, vaccine strains were selected to prepare inactivated vaccines. The whole-genome sequencing and analysis results showed that these seven representative FCV strains and 144 reference strains fell into five groups (A, B, C, D, and E). The strains isolated in China mainly fall into groups C and D, exhibiting regional characteristics. These Chinese isolates had a distant evolutionary relationship and low homology with the current FCV-255 vaccine strain. The screened FCV-HB7 and FCV-HB10 strains displayed desirable in vitro culture characteristics, with the highest virus proliferation titers (109.5 TCID50/mL) at 36 h post inoculation at a dose of 0.01 MOI. All five cats infected intranasally with FCV-HB7 or FCV-HB10 strains showed obvious clinical symptoms of FCV. The symptoms of cats infected with the FCV-HB7 strain were more severe than those infected with the FCV-HB10 strain. Both the single-strain inactivated immunization and combined bivalent inactivated vaccine immunization of FCV-HB7 and FCV-HB10 induced high neutralizing antibody titers in five cats immunized. Moreover, bivalent inactivated vaccine immunization protected cats from FCV-HB7 and FCV-HB10 strains. The cross-neutralizing antibody titer against seven representative FCV epidemic strains achieved by combined bivalent inactivated vaccine immunization was higher than that achieved by single-strain immunization, which was much higher than that achieved by commercial vaccine FCV-255 strain immunization. The above results suggest that the FCV-HB7 and FCV-HB10 strains screened in this study have great potential to become vaccine strains with broad-spectrum protective efficacy. However, their immune protective efficacy needs to be further verified by multiple methods before clinical application.

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Screening of a new candidate coxsackievirus B1 vaccine strain based on its biological characteristics.

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Screening of a new candidate coxsackievirus B1 vaccine strain based on its biological characteristics.

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