Haemophilus influenzae vaccine candidate outer membrane protein P6 is not conserved in all strains

Arthur Chang1, Ravinder Kaur, Lea Vacca Michel

  • 1Rochester General Hospital, Rochester General Research Institute, Center for Infectious Diseases and Immunology, Rochester, NY, USA.

Human Vaccines
|February 3, 2011
PubMed

Insights

Nontypeable Haemophilus influenzae P6 protein, a vaccine candidate, shows variations in structure among children. This finding challenges the assumption of P6 protein conservation in respiratory isolates.

Area of Science:

  • Microbiology
  • Immunology
  • Vaccine Development

Background:

  • Nontypeable Haemophilus influenzae (NTHi) is a significant pathogen, particularly in children.
  • The P6 outer membrane protein of NTHi is considered a conserved antigen and a potential vaccine candidate.
  • Conservation of P6 among H. influenzae strains is crucial for its vaccine efficacy.

Purpose of the Study:

  • To investigate the sequence and structural integrity of the P6 protein in NTHi isolates from children.
  • To determine if the P6 protein is truly conserved across NTHi strains causing respiratory infections and otitis media in pediatric populations.

Main Methods:

  • Analysis of P6 protein sequences from 151 NTHi isolates obtained from children (6-30 months old).
  • Identification of sequence mutations, non-homologous variations, and amino acid substitutions in the P6 protein.
  • Characterization of variants, including those affecting the binding site of a major antigenic epitope.

Main Results:

  • 14 out of 151 (9.3%) NTHi isolates exhibited variant P6 protein sequences.
  • One isolate showed mutations in the P6 binding site for monoclonal antibody 7F3, targeting a key epitope.
  • Eight isolates (5.3%) presented non-homologous variations potentially altering protein structure; five others had substitutions at critical residue sites.

Conclusions:

  • The P6 outer membrane protein of NTHi is not invariant in its structure among pediatric respiratory isolates.
  • Observed P6 variations may impact the effectiveness of P6-based vaccines.
  • Further research is needed to understand the implications of P6 structural diversity for NTHi pathogenesis and vaccine design.