Dengue NS1-specific antibody responses: Isotype distribution and serotyping in patients with dengue fever and dengue hemorrhagic fever

To understand the antibody responses to dengue (DEN) nonstructural 1 (NS1) glycoprotein and their roles in protective immunity or pathogenesis of deng ue fever (DF) and dengue hemorrhagic fever (DHF), we have analyzed the NS1- specific IgM, IgA and IgG antibodies from patients with DF and DHF. An isot ype-specific, indirect enzyme-linked immunosorbent assay (ELISA) was establ ished by coating a NS1-specific monoclonal antibody (MAb), D2/8-1, to captu re soluble NS1 antigens secreted in the culture supernatants of Vero cells infected with DEN virus. We observed strong anti-NS1 antibody responses in all of the convalescent sera of patients with DF and DHF. Similar NS1-speci fic isotypic and serotypic antibody responses were found in the sera from D F and DHF patients. The results showed that all DEN infections induced sign ificant NS1-specific IgG, whereas 75% and 60% of primary DF patients vs. 40 % and 90% of secondary DF patients produced IgM and IgA antibodies, respect ively. Specificity analysis showed that DEN NS1-specific IgG and IgA antibo dies cross-react strongly to Japanese encephalitis (JE) virus NS1 glycoprot ein, whereas DEN NS1-specific IgM antibodies do not crossreact to JE virus NS1 glycoprotein at ail. The serotype specificity of NS1-specific ISM, IgA and IgG were found to be 80%, 67% and 75% for primary infections, and 50%, 22% and 30% for secondary infections in positive samples of DF patients. Si milar pattern was found in DHF patients. The results showed that all of the DF and DHF patients produced significant NS1-specific antibodies. We did n ot observe direct correlation between the anti-NS1 antibody responses and D HF because sera from patients with DF and DHF showed similar anti- NS1 anti body responses. (C) 2000 Wiley-Liss, Inc.