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Published on: December 19, 2020
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.
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.
Abstract:
An outer membrane protein of nontypeable Haemophilus influenzae (NTHi), P6, is a vaccine candidate because it has been characterized as conserved among all H. influenzae strains. Among 151 isolates from children, age 6 to 30 months, evaluating NTHi nasopharyngeal (NP) and oropharyngeal (OP) colonization and tympanocentesis confirmed acute otitis media we identified 14 strains (9.3%) that had variant protein sequences of P6. One atypical omp P6 isolate had sequence mutations in the binding site of a proposed major antigenic epitope of omp P6 identified by monoclonal antibody 7F3. Eight strains (5.3%) had non-homologous variations in amino acids that could result in significant changes to the protein structure of P6, and 5 other strains had amino acid substitutions at four previously described key residue sites. These results show that NTHi omp P6 is not invariant in its structure among respiratory isolates from children.
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