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作者

Zhang, Zhenjie Dong, Zhaopeng Wang, Qian Carr, Michael J. Li, Juan Liu, Tao Li, Dong Shi, Weifeng

作者单位

Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical University, Taian 271000, China

刊名

Vaccine

年份

2018

卷号

Vol.36 No.46

页码

7095-7104

ISSN

0264-410X;1873-2518

关键词

Balanced protective immunity Bivalent vaccine Coxsackievirus A10 Coxsackievirus A6 Maternal antibody

摘要

Highlights • A bivalent CVA6 and CVA10 vaccine induced systemic antibody titers comparable to those of monovalent vaccines. • The bivalent vaccine could induce strong antigen-specific polyfunctional T cell immune responses. • Passive transfer of antisera from vaccinated mice protected recipient mice against virus challenge. • Maternal antibody could afford protection against challenge with homologous or heterologous CVA6, CVA10, or CVA6/CVA10. • There was no immunological interference between th...更多

Highlights • A bivalent CVA6 and CVA10 vaccine induced systemic antibody titers comparable to those of monovalent vaccines. • The bivalent vaccine could induce strong antigen-specific polyfunctional T cell immune responses. • Passive transfer of antisera from vaccinated mice protected recipient mice against virus challenge. • Maternal antibody could afford protection against challenge with homologous or heterologous CVA6, CVA10, or CVA6/CVA10. • There was no immunological interference between the CVA6 and CVA10 components of the bivalent vaccine. Abstract Coxsackievirus A6 and CVA10 are two of the major pathogens associated with hand, foot and mouth disease in children. The majority of CVA6 and CVA10 infections result in mild, self-limiting episodes in pediatric populations; however, in some cases, can proceed to severe neurological disease and death. Efforts to mitigate viral transmission to decrease the morbidity and mortality associated with infection would be greatly strengthened by the availability of an efficacious CVA6 and CVA10 bivalent vaccine. Here we report the immunogenicity and protective efficacy of a bivalent combination vaccine comprised of formaldehyde-inactivated, whole-virus CVA6 and CVA10. We demonstrate that subcutaneous delivery of the bivalent vaccine can induce antigen-specific systemic immune responses, particularly the induction of polyfunctional T cells, which elicit active immunization to achieve a protection rate of >80% in the infected neonatal mice. Furthermore, passive transfer of the antisera from vaccinated mice potently protected recipient mice against CVA6 and CVA10 challenge. Importantly, the bivalent vaccine could induce high levels of IgG and neutralizing antibodies in adult female mice and the maternal antibody transmitted to the recipient mice played an important role in controlling homotypic and heterotypic CVA6 and CVA10 infections and viral replication in vivo. Collectively, these findings indicate that there is no immunological interference between the two antigens with respect to their ability to induce virus-specific immune responses, and thus provides proof-of-concept for further development of multivalent vaccines for broad protection against HFMD.收起

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