High-molecular-weight adhesin 1 (HMW1)

High-molecular-weight adhesin 1 (HMW1) is a surface-exposed protein found in approximately 75-80% of nontypeable Haemophilus influenzae (NTHi) strains [2.1.2, 2.2.1]. It is a critical virulence factor that mediates bacterial attachment to human respiratory epithelial cells by binding to sialylated glycoproteins, particularly those with alpha 2-3-linked sialic acid [2.3.4, 3.1.2]. HMW1 is a member of the two-partner secretion (TPS) system and undergoes unique N-linked glycosylation by the cytoplasmic enzyme HMW1C, a modification essential for its stability and surface tethering [2.3.1, 2.3.2]. Due to its prominent role in the initial stages of colonization and its high immunogenicity, HMW1 is a major target of the human immune response and a leading candidate for the development of vaccines against NTHi-related diseases such as acute otitis media and pneumonia [2.2.2, 3.2.1]. While experimental vaccines targeting HMW1 have shown promise in animal models, the significant sequence variation between strains and the potential for phase variation present challenges for achieving broad-spectrum protection [3.1.1, 3.2.2]. Experimental strategies focus on using HMW1 as a vaccine antigen to induce protective antibodies that block adherence and promote opsonophagocytic killing of the bacteria [3.1.5, 3.2.4].

Other names

HMW1 proteinHigh-molecular-weight protein 1HMW1AHMW1 adhesin

Vaccine antigens induce protective antibodies that block bacterial adherence and promote opsonophagocytic killing; anti-adhesive agents block the interaction between HMW1 and host sialylated glycoproteins [2.2.2, 3.2.4].