Immunization with Haemophilus influenzae Hap adhesin protects against nasopharyngeal colonization in experimental mice

J Infect Dis. 2002 Oct 15;186(8):1115-21. doi: 10.1086/344233. Epub 2002 Sep 16.

Abstract

Nontypeable Haemophilus influenzae is a common cause of respiratory tract disease and initiates infection by colonizing the nasopharynx. The H. influenzae Hap adhesin is an autotransporter protein that was discovered because it promotes intimate interaction with human epithelial cells. Hap contains an extracellular domain called Hap(s) that has adhesive and protease activity and an outer membrane domain called Hap(beta) that serves to present Hap(s) on the surface of the cell. Hap(s) purified from nontypeable H. influenzae strain P860295 was used to immunize BALB/c mice intranasally. Immunization stimulated significant mucosal and serum anti-Hap(s) antibody titers, which were augmented by the addition of mutant cholera toxin (CT-E29H) as an adjuvant. Immunization was associated with a marked reduction in the density of nasopharyngeal colonization when mice were challenged with a heterologous strain of nontypeable H. influenzae. These results suggest that intranasal immunization with Hap formulated with CT-E29H may be a valuable vaccine strategy for the prevention of nontypeable H. influenzae disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / immunology
  • Bacterial Adhesion / immunology
  • Bacterial Outer Membrane Proteins / administration & dosage
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Blotting, Western
  • Cell Line
  • Cloning, Molecular
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / immunology
  • Haemophilus Infections / immunology*
  • Haemophilus Infections / prevention & control*
  • Haemophilus influenzae / immunology*
  • Immunity, Mucosal / immunology
  • Immunization
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Inbred BALB C
  • Nasopharynx / immunology*
  • Nasopharynx / microbiology*
  • Serine Endopeptidases*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Outer Membrane Proteins
  • Hap protein, Hemophilus influenzae
  • Immunoglobulin A
  • Immunoglobulin G
  • Serine Endopeptidases