title: Matrix protein-specific IgA antibody inhibits measles virus replication by intracellular neutralization.
abstract: Measles virus (MV) is still an imposing threat to public health. The matrix (M) protein has been shown not only to function as a structure block in the assembled MV virions, but also to regulate viral RNA synthesis, playing an important role in MV's replication and assembly. In the present study, we generated a panel of IgG monoclonal antibodies (MAbs) against M protein and successfully obtained one IgA MAb (5H7) from the IgG panel. Employing the polarized Vero cells grown in the two-chamber transwell model, we investigated whether M-specific 5H7 IgA MAb could suppress MV's replication and assembly. The data presented indicate that, while failing to show the activities of traditional neutralization and immune exclusion, M-specific IgA MAb was able to effectively inhibit viral replication by intracellular neutralization (78%), supporting the notion that the M protein is important for MV assembly and replication and implying that the M protein was an effective target antigen. The data also showed that MV had a long entry and assembly phase during viral replication, providing an extended window for IgA intervention. The colocalization of M proteins and M-specific 5H7 IgA MAbs demonstrated that the intracellular neutralization was due to the direct binding of the M-specific 5H7 IgA MAbs to the M proteins. In summary, the present study has added another example showing that IgA antibodies targeting internal viral antigens could proactively participate in mucosal immune protection by intracellular neutralization and has provided evidence that M protein might be included as a target antigen in future MV vaccine design.
authors.affiliation: Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Dihan
authors.initials: D
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Yaoqing
authors.initials: Y
authors.lastname: Chen
authors.forename: Benxia
authors.initials: B
authors.lastname: He
authors.forename: Jingyi
authors.initials: J
authors.lastname: Yang
authors.forename: Haobo
authors.initials: H
authors.lastname: Tu
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Huimin
authors.initials: H
authors.lastname: Yan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002522:Chlorocebus aethiops; D007070:Immunoglobulin A / Q000276:immunology*; D008459:Measles virus / Q000276:immunology* / Q000502:physiology*; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D014763:Viral Matrix Proteins