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

Zika virus(ZIKV)and dengue virus(DENV)belong to the family Flaviviridae and are mainly transmitted by Aedes aegypti mosquitoes.The outbreak of ZIKV in 2015 caused global concern,and subsequently the epidemic of ZIKV gradually expanded and overlapped with dengue virus.Dengue prM antibodies have been shown to be the primary antibodies with strong cross-reactivity mediating the antibody-dependent enhancement(ADE)of dengue virus.Recent studies have found that patients with a history of prior dengue virus infection can exhibit more severe clinical symptoms secondary to ZIKV infection,such as neonatal microcephaly and neurological impairment such as Guillain-Barre syndrome(GBS).There are still no specific antiviral drugs or effective vaccines to prevent ZIKV infection.Anti-idiotypic antibodies(AID)are antibodies induced by unique antigenic determinants on antibody molecules in homozygous or heterozygous species or in vivo,which recognize the antigenic epitopes of the original antibody and have high specificity and sensitivity.In our previous study,dengue prM anti-unique antibodies(prM-AIDs)were prepared and validated in an in vivo and vitro model to effectively inhibit the ADE effect of dengue prM antibodies mediated by dengue prM generated between dengue virus serotypes,and subsequently it was hypothesized that dengue prM-AIDs could have a similar effect on the ADE effect of ZIKV infection based on the high similarity between dengue and ZIKV.In this study,we verified that dengue patient serum and a commercial dengue prM monoclonal antibody could cross-react with ZIKV by ELISA and IF A.This indicates that the dengue prM antibody can effectively promote the infection of K562 cells by ZIKV at appropriate concentrations.The animal model of ZIKV ADE based on C57BL/6 was constructed.The ADE effect was determined by observing the pathological changes in the major organs,detecting the virus copy number in the blood of mice and the cytokine level in the serum,and statistical survival analysis.It was further verified in an in vivo model that the dengue prM antibody could effectively enhance ZIKV replication and activate natural immunity in vivo,the mechanism of action of which may be mediated by the Fc receptor.Subsequently,more potent prM-AIDs were obtained by immunizing New Zealand rabbits with murine-derived dengue prM monoclonal antibodies,and the protective effect of prM-AIDs against ZIKV infection was evaluated on cellular and animal models that had been previously constructed using prM-AIDs.The experimental results demonstrate that prM-AID can inhibit the ADE effect of ZIKV mediated by dengue prM antibody in vitro and in vivo,providing new ideas for the treatment of severe ZIKV disease,and the development of ZIKV vaccines.