MID and UspA1/A2 of the human respiratory pathogen Moraxella catarrhalis, and interactions with the human host as basis for vaccine development.

Abstract

Moraxella catarrhalis IgD-binding protein MID is a 200 kDa autotransporter protein that exists as a oligomer and is governed at the transcriptional level. The majority of M. catarrhalis clinical isolates expresses MID. Two functional domains have been attributed to MID; MID764-913 functions as an adhesin and promotes the bacteria to attach to epithelial cells, whereas the IgD-binding domain is located within MID962-1200. In parallel, MID is stimulatory for B lymphocytes through the IgD B cell receptor. M. catarrhalis ubiquitous surface proteins A1 and A2 (UspA1/A2) are multifunctional outer membrane proteins that can bind complement and extracellular matrix proteins such as vitronectin and fibronectin. An interaction between the complement fluid phase regulator of the classical pathway, C4b binding protein (C4BP), and UspA1/A2 has also been observed. Moreover, UspA1/A2 has a unique feature to interfere with the innate immune system of complement by binding C3. Taken together, a growing body of knowledge on M. catarrhalis outer membrane proteins MID and UspA1/A2 and their precise interactions with the human host make them promising vaccine candidates in a future multicomponent vaccine.