Transcutaneous immunization with a nontypeable Haemophilus influenzae dual adhesin-directed immunogen induces durable and boostable immunity.

Otitis media (OM) is a very common pediatric disease and nontypeable Haemophilus influenzae (NTHI) is the predominant causative agent. We've developed a chimeric immunogen, chimV4, that simultaneously targets two NTHI adhesins, OMP P5 and the type IV pilus. Transcutaneous immunization (TCI) via bandaid with chimV4 plus the adjuvant dmLT provides significant protection against experimental NTHI-induced OM in chinchilla models. Herein, we now examined the durability and boostability of the induced immune response. Bandaid immunization with chimV4+dmLT followed by two sequential middle ear challenges with NTHI resulted in rapid bacterial clearance and significantly accelerated disease resolution. Moreover, TCI with chimV4+dmLT significantly increased mature B-cell phenotypes and antibody-secreting cells within nasal-associated lymphoid tissues, a response that was further augmented upon TCI two months later. Thus, bandaid immunization induced durable and boostable immunity. The simplicity and non-invasive nature of TCI with chimV4+dmLT supports its utility as a highly effective additional immunization strategy for NTHI-induced OM.