Oral immunization with recombinant enterovirus 71 VP1 formulated with chitosan protects mice against lethal challenge

Virol J. 2014 May 6:11:80. doi: 10.1186/1743-422X-11-80.

Abstract

Background: Enterovirus 71 (EV71) is the etiologic agent of hand-foot-and-mouth disease (HFMD) in the Asia-Pacific region, Many strategies have been applied to develop EV71 vaccines but no vaccines are currently available. Mucosal immunization of the VP1, a major immunogenic capsid protein of EV71, may be an alternative way to prevent EV71 infection.

Results: In this study, mucosal immunogenicity and protect function of recombinant VP1 protein (rVP1) in formulation with chitosan were tested and assessed in female ICR mouse model. The results showed that the oral immunization with rVP1 induced VP1-specific IgA antibodies in intestine, feces, vagina, and the respiratory tract and serum-specific IgG and neutralization antibodies in vaccinated mice. Splenocytes from rVP1-immunized mice induced high levels of Th1 (cytokine IFN-γ), Th2 (cytokine IL-4) and Th3 (cytokine TGF-β) type immune responses after stimulation. Moreover, rVP1-immunized mother mice conferred protection (survival rate up to 30%) on neonatal mice against a lethal challenge of 103 plaque-forming units (PFU) EV71.

Conclusions: These data indicated that oral immunization with rVP1 in formulation with chitosan was effective in inducing broad-spectrum immune responses and might be a promising subunit vaccine candidate for preventing EV71 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Administration, Oral
  • Animals
  • Antibodies, Neutralizing / analysis
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / analysis
  • Antibodies, Viral / blood
  • Chitosan / administration & dosage*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enterovirus A, Human / genetics
  • Enterovirus A, Human / immunology*
  • Enterovirus Infections / immunology
  • Enterovirus Infections / prevention & control*
  • Female
  • Immunity, Mucosal
  • Immunoglobulin A / analysis
  • Immunoglobulin G / blood
  • Leukocytes, Mononuclear / immunology
  • Mice, Inbred ICR
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Spleen / immunology
  • Survival Analysis
  • Vaccination / methods*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Structural Proteins / genetics
  • Viral Structural Proteins / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Immunoglobulin A
  • Immunoglobulin G
  • Recombinant Proteins
  • Vaccines, Synthetic
  • Viral Structural Proteins
  • Viral Vaccines
  • Chitosan