High-molecular-weight adhesin 2 (HMW2)

High-molecular-weight adhesin 2 (HMW2) is a major surface-exposed glycoprotein and adhesin found in approximately 75-80% of nontypeable Haemophilus influenzae (NTHi) strains [1, 5]. It functions as a human-adapted lectin that mediates the initial attachment of the bacteria to the respiratory epithelium by specifically binding to 2-6 linked sialic acid glycans [4, 6]. This adherence is an essential first step in the pathogenesis of NTHi-related diseases, including otitis media, sinusitis, and pneumonia [8, 9]. HMW2 is highly immunogenic and serves as a primary target for the host's serum antibody response during natural infection [3, 20]. Due to its vital role in colonization and high prevalence, HMW2 is a prominent candidate for the development of subunit and DNA vaccines [11, 14]. Experimental evidence suggests that targeting HMW2 can induce protective immunity through both opsonophagocytic antibodies and IL-17A-mediated T-cell responses [5, 19]. However, therapeutic development faces challenges such as phase variation and antigenic heterogeneity among different bacterial strains [4, 13]. Current research focuses on identifying conserved motifs within the binding domains to ensure broad-spectrum protection across diverse NTHi isolates [13].

Other names

HMW2AHMW-2High-molecular-weight protein 2HMW2 protein

Vaccines and antibodies targeting HMW2 work by blocking bacterial adherence to host respiratory epithelial cells, promoting opsonophagocytosis, and inducing protective T-cell (IL-17A) responses to prevent colonization and subsequent infection.