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