A novel combined vaccine based on monochimeric VLP co-displaying multiple conserved epitopes against enterovirus 71 and varicella-zoster virus

Vaccine. 2017 May 9;35(20):2728-2735. doi: 10.1016/j.vaccine.2017.03.065. Epub 2017 Apr 10.

Abstract

Chicken pox and hand, foot and mouth disease (HFMD) are two major infectious diseases that mainly affect infants and children, causing significant morbidity annually. Varicella-zoster virus (VZV) and enterovirus 71 (EV71), respectively, are the principal epidemic pathogens causing these two diseases. To investigate the possibility of developing a novel combined vaccine to prevent chicken pox and HFMD, we constructed three chimeric virus-like particles (VLPs) (termed HBc-V/1/2, HBc-2/V/1 and HBc-1/2/V) based on the hepatitis B core antigen (HBc) carrier that display epitopes derived from VZV-gE, EV71-VP1, and EV71-VP2 in a varied tandem manner. The chimeric HBc can self-assemble into VLPs with these three epitopes displayed on the surface of particles. Epitope-specific antibody characterization suggested that HBc-V/1/2 elicits a balanced antibody response toward these three epitopes, and no immune interference was observed between the three epitopes. Importantly, the anti-HBc-V/1/2 sera could simultaneously neutralize VZV and EV71 and cross-neutralize coxsackievirus A16 (CVA16), another major pathogen causing HFMD. Moreover, the anti-HBc-V/1/2 sera protected neonatal mice from lethal challenge of EV71 and CVA16. Collectively, our study not only demonstrated that HBc-V/1/2 is a promising candidate combined vaccine for HFMD and Chicken pox but also provides a novel strategy for the design of combined vaccines.

Keywords: Combined vaccine; Enterovirus 71; Neutralizing epitopes; Varicella-zoster virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Chickenpox / prevention & control*
  • Drug Carriers
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / immunology*
  • Epitopes / genetics
  • Epitopes / immunology*
  • Female
  • Hand, Foot and Mouth Disease / prevention & control*
  • Hepatitis B Core Antigens / genetics
  • Herpesvirus 3, Human / genetics
  • Herpesvirus 3, Human / immunology*
  • Mice, Inbred BALB C
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / genetics
  • Vaccines, Combined / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Carriers
  • Epitopes
  • Hepatitis B Core Antigens
  • Vaccines, Combined
  • Vaccines, Synthetic
  • Vaccines, Virus-Like Particle
  • Viral Vaccines