Development of Novel Vaccines against Enterovirus-71

Abstract

The hand, foot and mouth disease is caused by a group of Enteroviruses such as Enterovirus 71 (EV-A71) and Coxsackievirus CV-A5, CV-A8, and CV-A16. Mild symptoms of EV-A71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents against EV-A71 to prevent further fatalities. Research groups have developed experimental inactivated vaccines, recombinant Viral Protein 1 (VP1) vaccine and virus-like particles (VLPs). The inactivated EV-A71 vaccine is considered the safest viral vaccine, as there will be no reversion to the infectious wild type strain. The recombinant VP1 vaccine is a cost-effective immunogen, while VLPs contain an arrangement of epitopes that can elicit neutralizing antibodies against the virus. As each type of vaccine has its advantages and disadvantages, increased studies are required in the development of such vaccines, whereby high efficacy, long-lasting immunity, minimal risk to those vaccinated, safe and easy production, low cost, dispensing the need for refrigeration and convenient delivery are the major goals in their design.

Keywords: Enterovirus 71; foot and mouth disease; hand; inactivated vaccine; viral like particles.

Figure 1

Structure and genome of Enterovirus 71. The capsid consists of 60 protomers, each consisting of four polypeptides that comprise the structural proteins: VP1, VP2, VP3, and VP4 and are encoded by the P1 region of the genome. The P2 and P3 regions encode for seven non-structural proteins: 2A–2C and 3A–3D (the EV-A71 genome is represented by the green line, followed by poly-A residues at the 3′UTR). Reproduced from ViralZone, with permission from Swiss Institute of Bioinformatics [12].

Figure 2

Vesicles on the foot, mouth and palm area of children infected with hand, foot and mouth disease (HFMD). Adapted from the Dermatologic Image Database, Department of Dermatology, University of Iowa College of Medicine, USA, 1996 (http://tray.dermatology.uiowa.edu/ImageBase). (Permission granted by University of Iowa) [19].