Anti-NS1 antibodies induced by immunization with dendritic cell targeted hybrid monoclonal antibodies do not induce platelet dysfunction.

Abstract

Dengue fever causes a disease whose symptoms range from asymptomatic to more severe, that may even lead to death. During infection, the non-structural (NS) 1 protein is produced in infected cells and subsequently shed to the circulation. Anti-NS1 antibodies have been implicated in disease pathogenesis as well as in protection against lethal infection. Here we analysed the role of anti-NS1 antibodies elicited when the NS1 protein was specifically targeted to two distinct dendritic cell (DC) subsets by chimeric monoclonal antibodies (mAbs) that bind to the DC surface receptors DEC205 and DCIR2. BALB/c mice received two doses of DEC-NS1 or DCIR2-NS1 mAbs in the presence of an adjuvant. We observed that anti-NS1 antibodies induced by immunization with chimeric DEC-NS1 or DCIR2-NS1 mAbs did not cause significant pathology or were able to protect BALB/c mice from an intracranial DENV2 NGC strain challenge.