Ubiquitous surface protein A2 (UspA2)

Ubiquitous surface protein A2 (UspA2) is a critical outer membrane protein and virulence factor of the Gram-negative bacterium Moraxella catarrhalis [1, 4]. It belongs to the family of trimeric autotransporter adhesins (TAAs) and forms a characteristic lollipop-shaped structure on the bacterial surface [4, 7]. UspA2 plays a dual role in pathogenesis by mediating adhesion to host extracellular matrix proteins, such as laminin and fibronectin, and providing resistance to the host's innate immune system [9, 11, 12]. Specifically, it confers serum resistance by binding to complement inhibitors like C4b-binding protein (C4BP), vitronectin, and Factor H, thereby preventing complement-mediated lysis [13, 15]. Due to its essential role in bacterial survival and its presence in nearly all clinical isolates, UspA2 is a primary target for vaccine development and monoclonal antibody therapies aimed at preventing otitis media in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults [1, 2, 4]. Investigational vaccines and fusion proteins targeting UspA2 work by inducing bactericidal antibodies or displacing complement inhibitors to enhance bacterial clearance [1, 13].

Other names

UspA2Ubiquitous surface protein A2UspA2HOca proteinOligomeric coiled-coil adhesinTrimeric autotransporter adhesin UspA2

Vaccines containing UspA2 induce bactericidal antibodies that promote complement-mediated killing and inhibit bacterial adhesion to host tissues [1, 2]. Monoclonal antibodies and fusion proteins target UspA2 to neutralize its function, displace host complement inhibitors (such as Factor H or C4BP), and enhance opsonophagocytosis or complement-mediated lysis of the bacteria [4, 13].