Summary auto-generated
This study identifies a new protective antibody epitope on the measles virus hemagglutinin (H) protein. Researchers generated monoclonal antibodies that recognize amino acids 244-250 (SELSQLS) of the H protein, a linear neutralizing epitope distinct from previously known sites. These antibodies uniquely prevent viral fusion without blocking initial virus binding to cells, contrasting with most other H-specific antibodies that inhibit binding. The epitope was mapped using synthetic peptides and truncation analysis. Notably, all four antibodies (BH47, BH59, BH103, BH129) provided complete protection against lethal measles challenge in mice, even at low doses. Competition assays demonstrated this site is topographically and functionally separate from another known epitope (HNE), suggesting it may represent an interface between the H and F fusion proteins. The proximity to amino acid 243, involved in CD46 receptor downregulation, hints at a functional connection to receptor interaction. These findings suggest the newly described epitope could be valuable for developing peptide-based subunit vaccines against measles.
Key findings
- A linear neutralizing epitope (H244-250: SELSQLS) on measles virus hemagglutinin was identified using monoclonal antibodies that prevent viral fusion without blocking initial virus binding
- These fusion-inhibiting antibodies are topographically and functionally distinct from previously known hemagglutinin epitopes, suggesting a specific interface with the fusion protein
- Monoclonal antibodies to this epitope provided complete protection against lethal measles encephalitis challenge in mice across multiple dose levels
- The epitope is a short linear sequence that can be recognized by synthetic peptides, making it a promising candidate for peptide-based subunit vaccine design
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Abstract
The haemagglutinin protein (H) of measles virus (MV) binds to susceptible cells and collaborates with the fusion protein (F) to mediate fusion of the virus with the cell membrane. Binding and fusion activity of the virus can be monitored by haemagglutination and haemolysis, respectively, of monkey erythrocytes. Most monoclonal antibodies (MAbs) with haemolysis inhibiting activity (HLI+) are either MV-F specific and do not inhibit haemagglutination (HI-), or they bind to MV-H and are HI+ by interfering with virus binding. We describe here a small panel of H-specific MAbs (BH47, BH59, BH103, BH129) which bind to a new linear neutralizing epitope, H244-250 (SELSQLS; NE domain), and which prevent virus-cell fusion (HLI+) but not virus binding (HI-). These antibodies also protect against MV encephalitis in an animal model. They do not compete with an HLI+/HI+ antibody (BH216) which binds to the haemagglutinin noose epitope (HNE). The antibodies described here and the HNE-specific antibodies are functionally distinct and define two topographically non-overlapping interfaces, supposedly with a bias towards the host cell MV-receptor and the fusion protein respectively. The proximity of the CD46 downregulating amino acid Arg-243 may suggest a functional link between the domain described here and the CD46 binding domain. This new protective linear site is also of potential interest for the design of a subunit-based vaccine.