Evaluation of the protective immunity of a novel subunit fusion vaccine in a murine model of systemic MRSA infection

PLoS One. 2013 Dec 4;8(12):e81212. doi: 10.1371/journal.pone.0081212. eCollection 2013.

Abstract

Staphylococcus aureus is a common commensal organism in humans and a major cause of bacteremia and hospital acquired infection. Because of the spread of strains resistant to antibiotics, these infections are becoming more difficult to treat. Therefore, exploration of anti-staphylococcal vaccines is currently a high priority. Iron surface determinant B (IsdB) is an iron-regulated cell wall-anchored surface protein of S. aureus. Alpha-toxin (Hla) is a secreted cytolytic pore-forming toxin. Previous studies reported that immunization with IsdB or Hla protected animals against S. aureus infection. To develop a broadly protective vaccine, we constructed chimeric vaccines based on IsdB and Hla. Immunization with the chimeric bivalent vaccine induced strong antibody and T cell responses. When the protective efficacy of the chimeric bivalent vaccine was compared to that of individual proteins in a murine model of systemic S. aureus infection, the bivalent vaccine showed a stronger protective immune response than the individual proteins (IsdB or Hla). Based on the results presented here, the chimeric bivalent vaccine affords higher levels of protection against S. aureus and has potential as a more effective candidate vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibody Formation / immunology
  • Antigens, Bacterial / immunology
  • Chemokines / biosynthesis
  • Cloning, Molecular
  • Disease Models, Animal
  • Immunity*
  • Immunization
  • Immunoglobulin G / immunology
  • Male
  • Methicillin-Resistant Staphylococcus aureus / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Opsonin Proteins / immunology
  • Phagocytosis
  • Recombinant Fusion Proteins / immunology*
  • Spleen / immunology
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Vaccines / immunology*
  • T-Lymphocytes / immunology
  • Vaccines, Subunit / immunology*

Substances

  • Antibodies, Neutralizing
  • Antigens, Bacterial
  • Chemokines
  • Immunoglobulin G
  • Opsonin Proteins
  • Recombinant Fusion Proteins
  • Staphylococcal Vaccines
  • Vaccines, Subunit

Grants and funding

This research was supported by National Natural Science Foundation of China (Grant NO: 81172892) and by NSFC-NIH International Cooperation Grant (NO: 81261120396) and by Natural Science Foundation of Chongqing (Grant NO: CSTC2011jjA10071). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.