From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mou
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REVIEW
From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease (HFMD) Xiangchuan He1 • Miaomiao Zhang1 • Chen Zhao1 • Peiyong Zheng2 • Xiaoyan Zhang1
•
Jianqing Xu1
Received: 22 April 2020 / Accepted: 25 August 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract Hand, foot, and mouth disease (HFMD) recently emerged as a global public threat. The licensure of inactivated enterovirus A71 (EV-A71) vaccine was the first step in using a vaccine to control HFMD. New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage. The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines. The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes. The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a crossprotective antibody response. Keywords Hand, foot, and mouth disease (HFMD) Inactivated whole virus vaccine Virus-like particles Multivalent vaccines Chimeric vaccines
Introduction Human hand-foot-and-mouth disease (HFMD) caused several large outbreaks across the Asian-Pacific region, and it represents a global public health issue. Several viruses were identified as the primary HFMD-related pathogens, and this list includes enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), CV-A6 and CV-A10, which all belong to the genus Enterovirus within the Picornaviridae family (Fang and Liu 2018). HFMD frequently occurs in children under five years old, and it is generally characterized by vesicular exanthema with self-limitation. There appears to be a link between the range of clinical & Jianqing Xu [email protected] & Xiaoyan Zhang [email protected] 1
Shanghai Public Health Clinical Center and Institutes of Biomedical Science, Shanghai Medical College, Fudan University, Shanghai 201508, China
2
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
manifestations and serotype differences, with some EVA71 infections resulting in severe complications, including brainstem encephalitis, aseptic meningitis, acute flaccid paralysis, cardiopulmonary failure, or death, but other serotypes generally showing mild symptoms (Lin et al. 2019). Historically, EV-A71 and CV-A16 primarily accounted for the global HFMD outbreaks; however, other serotypes are gradually gaining dominance due to the broad inoculation of and protection by inactivated EV-A71 vaccines. Indeed, CV-A6 displaced EV-A71 and CV-A16 as the predominant serotype in 2013 in Shanghai, and CVA10 has gradually become the dominating HFMD-related enterovirus (Song et al. 2017;
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