Update on non-typeable Haemophilus influenzae-mediated disease and vaccine development.

INTRODUCTION: Non-typeable Haemophilus influenzae (NTHi) has attracted more interest in recent years due to an increased prevalence of infections caused by the pathogen. This upsurge is at least partly ascribed to the introduction of the pneumococcal conjugated vaccines that has resulted in an aetiological shift in NTHi's favor with respect to upper respiratory tract infections. Moreover, an increased antimicrobial resistance has been associated with the pathogen, a fact that further strengthens the case for novel vaccine development. AREAS COVERED: A background to NTHi-mediated diseases and pathogenesis is outlined. The literature in the field of NTHi vaccine antigens and clinical trials is reviewed with focus on data added to scientific databases in the last two years. Various vaccine development strategies are conceptually discussed. EXPERT COMMENTARY: Several promising vaccine antigens have been defined in recent years. A multicomponent protein-based vaccine, potentially boosted with extracellular vesicles, would constitute a suitable path going forward. Of note, however, a clinical trial investigating the efficacy of a combined NTHi/Moraxella catarrhalis vaccine to prevent infections in chronic obstructive pulmonary disease (COPD) patients has been initiated. But, as this clinical trial has not yet concluded, and its results are thus unknown, investigations of NTHi pathogenesis must determinedly continue.