2007
DOI: 10.1128/cvi.00371-06
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Antibody Responses Are Generated to Immunodominant ELK/KLE-Type Motifs on the Nonstructural-1 Glycoprotein during Live Dengue Virus Infections in Mice and Humans: Implications for Diagnosis, Pathogenesis, and Vaccine Design

Abstract: Antibodies generated to the purified dengue type 2 virus (D-2V) nonstructural-1 (NS1) protein in mice and rabbits were compared with those generated to this protein in congeneic (H-2 class II) mouse strains and humans after D-2V infections. Unlike the profiles observed with the rabbits, similar antibody reaction profiles were generated by mice and humans with severe D-2V disease (dengue hemorrhagic fever [DHF]/dengue shock syndrome [DSS]). Many of these epitopes contained the core acidic-hydrophobic-basic (tri… Show more

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Cited by 60 publications
(104 citation statements)
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“…Statistical significance was P 0.05. infection may be related to inefficient detection of NS1 during secondary infections. [35][36][37][38] In summary, these results suggest that during primary infections, levels of circulating NS1 are higher in patients with DHF than in patients with DF. Nonetheless, our results and other results 18,20 also suggest that concentrations of circulating NS1 are affected by the infecting serotype and the immunologic status (i.e., primary or secondary infection) of the patient.…”
Section: Discussionmentioning
confidence: 72%
“…Statistical significance was P 0.05. infection may be related to inefficient detection of NS1 during secondary infections. [35][36][37][38] In summary, these results suggest that during primary infections, levels of circulating NS1 are higher in patients with DHF than in patients with DF. Nonetheless, our results and other results 18,20 also suggest that concentrations of circulating NS1 are affected by the infecting serotype and the immunologic status (i.e., primary or secondary infection) of the patient.…”
Section: Discussionmentioning
confidence: 72%
“…Indirect ELISAs and immunoblot assays using purified DENV-2 particles and the DENV-2 NS1 glycoprotein were described previously (7,10). For ELISA, optimal concentrations of purified DENV-2 particles (1/250 dilution; 0.58 g/ml) and DENV-2 eNS1 glycoprotein (2 to 3 g/ml) were diluted in 0.16%/0.29% (wt/vol) sodium carbonate/bicarbonate (pH 9.8), loaded at 50 l/well into ELISA plates (Immulon 2; Dynatech), and adsorbed overnight at 4°C.…”
Section: Methodsmentioning
confidence: 99%
“…Three other MAbs generated to the DENV-2 NS1 protein also recognized short sequential amino acid sequences. MAb 1C6.3 reacted more specifically with multiple KELK-type motifs present in either orientation (KELK/KLEK-type motifs), MAb 3D1.4 recognized the LX1 (113-YSWKTWG-119) epitope, and MAb 1G5.3 recognized the 24C (301-TTASGKLIT-309) epitope (7,9,12).…”
mentioning
confidence: 99%
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“…Furthermore, the anti-NS1 antibodies elicited at high titers during infection may form immune complexes with NS1, which trigger the inflammatory response and bind some coagulation elements to deregulate vascular permeability (13,14). Conversely, active or passive immunization with NS1 promotes the survival of DENVchallenged mice, making it an attractive target for vaccine development (15-17).…”
mentioning
confidence: 99%