The Protective Role Of Anti-idiotype Antibodies Specific To PrM Antibody Against Dengue Virus Infection

Dengue virus(DENV),a flaviviridae,comprises four related but antigenically distinct DENV serotypes(DENV1-4)with positive single-stranded RNA genome.Dengue virus co-circulates as four serotypes(DENV1-4).Primary infection only leads to self-limited dengue fever.But secondary infection with another serotype carries a higher risk of increased disease severity,causing life-threatening dengue hemorrhagic fevwer/dengue shock syndrome(DHF/DSS).Serotype cross-reactive antibodies facilitate DENV infection in Fc-receptor-bearing cells by promoting virus entry via Fcγ receptors(FcγR),a process known as antibody dependent enhancement(ADE).Most studies suggested that enhancing antibodies were mainly specific to the structural premembrane protein(prM)of DENV.In this study,interestingly,we found that a rabbit polyantiody against DENV-2 displayed neutralizing not enhancing activity to DENV-1.Besides,the result of qRT-PCR and flow cytometry confirmed that both DENV-2 infected human serum(anti-DENV-2)and DENV-2 prM monoclonal antibody(prM m Ab)could significantly enhance DENV-1 infection in K562 cells.Then we developed anti-idiotypic antibodies(prM-AIDs)specific to prM mAb by immunization to Balb/c mice.Results showed that prM-AIDs were capable to dramatically diminished ADE induced by prM mAb through decreasing 90% viral replication.To further confirm the anti-ADE effect of prM-AIDs in vivo,an interferon-α and γ receptor-deficient mice(AG6)was used to be a mouse model for DENV1 infection.Viral load in blood cells was detected by qRT-PCR,while live virus particles in plasma was detected by plaque assay.Platelets were counted under common microscope,and alanine aminotransferase(ALT),interleukin 10(IL-10)in the plasma were detected by ELISA at day 3 post infection.We found that DENV-2 prM mAb indeed caused a higher DENV-1 titre as well as interleukin-10(IL-10)and alanine aminotransferase(ALT),similar to clinical ADE symptoms.But when we transferred prM-AIDs to DENV-1 challenged AG6 mice,the viral titer,IL-10 and ALT were obviously decreased to the negative control level.Of note,the number of platelets in peripheral blood of prM-AIDs group were significantly increased at day 3 post infection with DENV-1 compared that of prM-mAb group.These results confirmed that our prM-AIDs could prevent ADE not only in vitro but also in vivo,sμggested that anti-idiotypic antibodies might be a new choice to be considered to treat DENV infection.