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Review
. 2022 Dec 22;24(1):169.
doi: 10.3390/ijms24010169.

Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines

Xinglong Zhang  1 , Yifan Zhang  1 , Heng Li  1 , Longding Liu  1
Affiliations
Review

Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines

Xinglong Zhang et al. Int J Mol Sci. .

Abstract

Hand-foot-and-mouth disease (HFMD) is an infectious disease of children caused by more than 20 types of enteroviruses, with most cases recovering spontaneously within approximately one week. Severe HFMD in individual children develops rapidly, leading to death, and is associated with other complications such as viral myocarditis and type I diabetes mellitus. The approval and marketing of three inactivated EV-A71 vaccines in China in 2016 have provided a powerful tool to curb the HFMD epidemic but are limited in cross-protecting against other HFMD-associated enteroviruses. This review focuses on the epidemiological analysis of HFMD-associated enteroviruses since the inactivated EV-A71 vaccine has been marketed, collates the progress in the development of multivalent enteroviruses vaccines in different technical routes reported in recent studies, and discusses issues that need to be investigated for safe and effective HFMD multivalent vaccines.

Keywords: HFMD; multivalent vaccines; systemic immunity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The epidemiological data of HFMD. (a) The number of HFMD cases in China from 2008 to 2021 and the ranking of its morbidity among C infectious diseases. The data in the figure are cited from www.chinacdc.cn (accessed on 10 October 2022). (b) The fatality rate of HFMD in China from 2008 to 2021 and its ranking among category C infectious diseases. The data in the figure are cited from www.chinacdc.cn (accessed on 10 October 2022). (c) The rate of severe HFMD illnesses before and after the first inactivated EV-A71 vaccine was approved in China. The data in the figure are cited from [23]. (d) Seropositivity rates of different HFMD-associated enteroviruses in Vietnam and Korea. The data in the figure are cited from [24,25].
Figure 2
Figure 2
Seropositivity rates of different HFMD-associated enteroviruses in the whole of China along with the Chengdu and Kunming areas, 2013–2020. (a) Seropositivity rates of different HFMD-associated enteroviruses in the whole of China, 2013–2019. The data in the figure are cited from [26]. (b) Seropositivity rates of different HFMD-associated enteroviruses in Chengdu, Sichuan province, China. The data in the figure are cited from [27]. (c) Seropositivity rate of different HFMD-associated enteroviruses before EV-A71 inactivated vaccine vaccination in Kunming, Yunnan Province, China. The data in the figure are cited from [28]. (d) Seropositivity rate of different HFMD-associated enteroviruses after EV-A71 inactivated vaccine in Kunming, Yunnan Province, China. The data in the figure are cited from [29].
Figure 3
Figure 3
The potential mechanism that intradermal immunization is more effective than intramuscular immunization. Image created with BioRender (https://biorender.com/, accessed on 10 October 2022).
Figure 4
Figure 4
A series of potential methods to get more balanced immune responses and a broader spectrum of protective immune responses in development of multivalent HFMD vaccines. Image created with BioRender (https://biorender.com/, accessed on 10 October 2022).
See this image and copyright information in PMC

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