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Immunogenicity and protective efficacy of inactivated coxsackievirus B4 viral particles
Tingfeng Wang1,2, Chiyuan Wang1, Lili Pang2
1Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, People's Republic of China.
Insights
New inactivated Coxsackievirus B4 (CVB4) vaccines, using F-particles and E-particles, effectively generate neutralizing antibodies and protect mice from lethal CVB4 infection. This research advances potential CVB4 vaccines.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Coxsackievirus B4 (CVB4) causes severe diseases like type 1 diabetes and myocarditis in millions of children globally.
- Currently, no preventive vaccine exists for CVB4 infections.
Purpose of the Study:
- To develop and evaluate inactivated viral particle vaccines for Coxsackievirus B4.
- To assess the immunogenicity and protective efficacy of two distinct inactivated CVB4 vaccine candidates.
Main Methods:
- Preparation of two types of inactivated CVB4 particles: F-particle (mature virion) and E-particle (empty capsid).
- Immunization of mice with inactivated CVB4 particles.
- Measurement of neutralizing antibody responses.
- Evaluation of protective efficacy through passive antibody transfer and lethal CVB4 challenge.
Main Results:
- Both inactivated F-particle and E-particle vaccines potently elicited neutralizing antibodies in mice.
- Passive transfer of antisera against both F-particle and E-particle conferred complete protection against lethal CVB4 challenge.
- E-particle vaccines showed slightly lower neutralizing antibody titers after the third immunization compared to F-particle vaccines.
Conclusions:
- Inactivated CVB4 F-particle and E-particle vaccines demonstrate significant immunogenicity and protective efficacy in a mouse model.
- Neutralizing antibodies play a critical role in protective immunity against CVB4.
- These findings provide crucial data to accelerate the development of effective inactivated CVB4 vaccines.
Abstract:
Coxsackievirus B4 (CVB4) is associated with a range of acute and chronic diseases such as hand, foot, and mouth disease, myocarditis, meningitis, pancreatitis, and type 1 diabetes, affecting millions of young children annually around the world. However, no vaccine is currently available for preventing CVB4 infection. Here, we report the development of inactivated viral particle vaccines for CVB4. Two types of inactivated CVB4 particles were prepared from CVB4-infected cell cultures as vaccine antigens, including F-particle (also called mature virion) consisting of VP1, VP3, VP2, and VP4 subunit proteins, and E-particle (also called empty capsid) which is made of VP1, VP3, and uncleaved VP0. Both the inactivated CVB4 F-particle and E-particle were able to potently elicit neutralizing antibodies in mice, despite slightly lower neutralizing antibody titres seen with the E-particle vaccine after the third immunization. Importantly, we demonstrated that passive transfer of either anti-F-particle or anti-E-particle sera could completely protect the recipient mice from lethal CVB4 challenge. Our study not only defines the immunogenicity and protective efficacy of inactivated CVB4 F-particle and E-particle but also reveals the central role of neutralizing antibodies in anti-CVB4 protective immunity, thus providing important information that may accelerate the development of inactivated CVB4 vaccines.
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