Summary
NTHi is a highly adapted human commensal and opportunistic lower
airway pathogen possessing multi-function virulence factors exhibiting
efficient adherence, immune evasion and nutrient scavenging properties.
These allow it to invade cells and form biofilms in order to survive
within the lungs of children with CSLD. The molecular pathogenesis ofNTHi is not fully understood and large knowledge gaps exist over
its mechanistic role in progressive lung disease. Identifying critical
cellular pathways and, including host-pathogen cross-talk and
interactions with other lung microbes, are crucial for developing novel
therapeutic agents and vaccine candidates (Box).132NTHi vaccines are an active area of research, but NTHi strains
have both marked genetic heterogeneity from recombination with otherNTHi and phase-variability, and no vaccine candidate is ready for
large field trials. Two recent, relatively small vaccine trials, one in
children with CSLD targeting NTHi protein D in the
PHiD-CV vaccine and another in adults with COPD targeting threeNTHi surface proteins, failed to meet their primary outcome of
reducing exacerbations, despite both demonstrating good immunogenicity
highlighting that further mechanistic studies are needed involvingNTHi and patients with CSLD.133,134