Analysis of cross-reactive antibodies recognizing the fusion loop of envelope protein and correlation with neutralizing antibody titers in Nicaraguan dengue cases.
Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. The envelope (E) protein of DENV is the major target of neutralizing antibodies (Abs). Previous studies have shown that a significant proportion of anti-E Abs in human serum after DENV infection recognize the highly conserved fusion loop (FL) of E protein. The role of anti-FL Abs in protection against subsequent DENV infection versus pathogenesis remains unclear. A human anti-E monoclonal Ab was used as a standard in a virion-capture ELISA to measure the concentration of anti-E Abs, [anti-E Abs], in dengue-immune sera from Nicaraguan patients collected 3, 6, 12 and 18 months post-infection. The proportion of anti-FL Abs was determined by capture ELISA using virus-like particles containing mutations in FL, and the concentration of anti-FL Abs, [anti-FL Abs], was calculated. Neutralization titers (NT50) were determined using a previously described flow cytometry-based assay. Analysis of sequential samples from 10 dengue patients revealed [anti-E Abs] and [anti-FL Abs] were higher in secondary than in primary DENV infections. While [anti-FL Abs] did not correlate with NT50 against the current infecting serotype, it correlated with NT50 against the serotypes to which patients had likely not yet been exposed ("non-exposed" serotypes) in 14 secondary DENV3 and 15 secondary DENV2 cases. These findings demonstrate the kinetics of anti-FL Abs and provide evidence that anti-FL Abs play a protective role against "non-exposed" serotypes after secondary DENV infection.
Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, United States of America.
Chih-Yun
CY
Lai
Katherine L
KL
Williams
Yi-Chieh
YC
Wu
Sarah
S
Knight
Angel
A
Balmaseda
Eva
E
Harris
Wei-Kung
WK
Wang
D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D008297:Male; D009500:Neutralization Tests; D009527:Nicaragua; D014760:Viral Fusion Proteins / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014760:Viral Fusion Proteins