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Published on: October 11, 2013
Screening of a potential coxsackievirus B4 vaccine strain through analysis of biological features
Wei Guo1,2, Xiang Li1, Junwei Chen1,3
1Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People's Republic of China.
Abstract:
Coxsackievirus B4 (CVB4) is a major pathogen involved in hand, foot, and mouth disease as well as aseptic meningitis, and is associated with type 1 diabetes mellitus. Currently, no effective antiviral drugs or vaccines are available for CVB4 infections. Drawing on successful experience with inactivated vaccines for enterovirus 71 and poliovirus, we developed an inactivated CVB4 vaccine based on Vero cells. The highly pathogenic CVB4 virus strain 140/CHN/2019, isolated from Vero cells and classified as genotype D, reflecting the circulating strains in China. Through three cycles of plaque assays and successive passages, the clone strain KM140-G01 could adapt to Vero cells and grew to a titer exceeding 10⁷ CCID50/mL. The experimentally inactivated CVB4 vaccine, developed from KM140-G01, effectively elicited high levels of neutralizing antibodies in BALB/c mice, with titers ranging from Log2 7.2 to 11.0 and effectively neutralized various clinical isolates (> Log210). Maternal antibodies provided 100% protection against a lethal challenge with CVB4 isolates in lactating BALB/c mice. Therefore, the KM140-G01 strain in this study is a viable new candidate for the development of a coxsackievirus B4 vaccine. The CVB4-infected neonatal mouse model should substantially facilitate CVB4 vaccine evaluation.
Insights
An inactivated Coxsackievirus B4 (CVB4) vaccine candidate, derived from the KM140-G01 strain, shows promise. This vaccine effectively induced neutralizing antibodies in mice and offers potential for CVB4 prevention.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Coxsackievirus B4 (CVB4) is a significant pathogen causing hand, foot, and mouth disease, aseptic meningitis, and type 1 diabetes.
- Current therapeutic options for CVB4 infections are limited, with no approved antiviral drugs or vaccines available.
Purpose of the Study:
- To develop and evaluate an inactivated Coxsackievirus B4 vaccine candidate.
- To assess the immunogenicity and protective efficacy of the candidate vaccine in preclinical models.
Main Methods:
- Development of an inactivated CVB4 vaccine using the Vero cell-adapted strain KM140-G01.
- Evaluation of vaccine immunogenicity through antibody titer measurements in BALB/c mice.
- Assessment of vaccine efficacy via lethal challenge studies and maternal antibody protection models.
Main Results:
- The CVB4 strain KM140-G01 was adapted to Vero cells, achieving high titers (>10⁷ CCID₅₀/mL).
- The inactivated vaccine elicited high levels of neutralizing antibodies (Log₂ 7.2–11.0) and neutralized diverse clinical isolates (>Log₂10).
- Maternal antibodies conferred 100% protection against lethal CVB4 challenge in neonatal mice.
Conclusions:
- The KM140-G01 strain is a viable candidate for developing a CVB4 vaccine.
- The developed inactivated CVB4 vaccine demonstrates significant immunogenic and protective potential.
- The CVB4 neonatal mouse model is suitable for future vaccine evaluations.
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