Attenuation of coxsackievirus B3 by VP2 mutation and its application as a vaccine against virus-induced myocarditis and pancreatitis

Vaccine. 2009 Mar 18;27(13):1974-83. doi: 10.1016/j.vaccine.2009.01.008. Epub 2009 Jan 23.

Abstract

Coxsackievirus B3 (CVB3) is a common agent of viral myocarditis, a major cause of sudden cardiac death, and ultimately dilated cardiomyopathy. However, there is no vaccine in clinical use. In this study, we identified the conserved amino acid sequences in the C-terminal region of the VP2 of the coxsackievirus B group and some echoviruses. The mutant virus, YYFF, with phenylalanines substituted for two tyrosines in these conserved sequences was highly attenuated in vivo and could induce a high neutralizing antibody titer and a cytotoxic T-lymphocyte response against CVB3. Thereby, mutant-virus-immunized mice showed a 100% survival rate and protection against inflammation of the heart and pancreas after lethal dose challenge. Thus, this mutant virus is a good candidate for an attenuated CVB3 vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Conserved Sequence
  • Coxsackievirus Infections / complications
  • Coxsackievirus Infections / prevention & control*
  • Enterovirus / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Myocarditis / etiology
  • Myocarditis / prevention & control*
  • Myocarditis / virology
  • Neutralization Tests
  • Pancreatitis / etiology
  • Pancreatitis / prevention & control*
  • Pancreatitis / virology
  • Protein Structure, Tertiary
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, Attenuated / immunology
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • Vaccines, Attenuated
  • Viral Vaccines