Enteroviruses: epidemic potential, challenges and opportunities with vaccines

Abstract

Enteroviruses (EVs) are the most prevalent viruses in humans. EVs can cause a range of acute symptoms, from mild common colds to severe systemic infections such as meningitis, myocarditis, and flaccid paralysis. They can also lead to chronic diseases such as cardiomyopathy. Although more than 280 human EV serotypes exist, only four serotypes have licenced vaccines. No antiviral drugs are available to treat EV infections, and global surveillance of EVs has not been effectively coordinated. Therefore, poliovirus still circulates, and there have been alarming epidemics of non-polio enteroviruses. Thus, there is a pressing need for coordinated preparedness efforts against EVs.This review provides a perspective on recent enterovirus outbreaks and global poliovirus eradication efforts with continuous vaccine development initiatives. It also provides insights into the challenges and opportunities in EV vaccine development. Given that traditional whole-virus vaccine technologies are not suitable for many clinically relevant EVs and considering the ongoing risk of enterovirus outbreaks and the potential for new emerging pathogenic strains, the need for new effective and adaptable enterovirus vaccines is emphasized.This review also explores the difficulties in translating promising vaccine candidates for clinical use and summarizes information from published literature and clinical trial databases focusing on existing enterovirus vaccines, ongoing clinical trials, the obstacles faced in vaccine development as well as the emergence of new vaccine technologies. Overall, this review contributes to the understanding of enterovirus vaccines, their role in public health, and their significance as a tool for future preparedness.

Keywords: EV outbreaks; EV surveillance; Enterovirus (EV); Vaccine development.

Fig. 1

Enterovirus genome organisation and capsid structure (not to scale). A enterovirus genome encodes a single polyprotein (regions P1-P3) comprising a main open reading frame (ORF). Additional recently discovered [3, 4] ORF2 overlaps with the main ORF at the 5’ end. The ORF2 is not found from rhinoviruses or EV-D68 [4] B enterovirus capsid is formed by the four viral structural proteins VP1-VP4 of which the VP4 is located at the inner capsid, C while VP1-VP3 form a pseudo T=3 symmetry unit (highlighted with neon green) which assembles into pentamers 12 of which in turn form the outer capsid

Fig. 2

Enterovirus replication cycle (schematic representation). After receptor attachment and internalization by endocytosis, the genome is uncoated. As positive stranded RNA viruses, enteroviruses utilise host-cell machinery in genome replication – the replication takes place in a replication organelle, which are composed of cellular membranes prompted by the infection. After assembly the mature virions are released by either lytic or non-lytic pathways

Fig. 3

The enterovirus vaccine landscape in clinical trials. Majority of enterovirus vaccine clinical trials are conducted for polio- and EV-A71 vaccines. In addition to those, single phase I clinical trial has been completed for CVB1 vaccine [79] (not shown in the figure). Based on www.clinicaltrials.cov search

Fig. 4

The enterovirus vaccine landscape prior to clinical trials. The figure depicts enterovirus vaccines in A preclinical trials and B enterovirus vaccine technologies in preclinical trials. Based on www.adisinsight.com search