Blockade-of-Binding Activities toward Envelope-Associated, Type-Specific Epitopes as a Correlative Marker for Dengue Virus-Neutralizing Antibody
Issued Date
2023-08-17
Resource Type
eISSN
21650497
Scopus ID
2-s2.0-85168242022
Pubmed ID
37409936
Journal Title
Microbiology spectrum
Volume
11
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Microbiology spectrum Vol.11 No.4 (2023) , e0091823
Suggested Citation
Keelapang P., Kraivong R., Pulmanausahakul R., Sriburi R., Prompetchara E., Kaewmaneephong J., Charoensri N., Pakchotanon P., Duangchinda T., Suparattanagool P., Luangaram P., Masrinoul P., Mongkolsapaya J., Screaton G., Ruxrungtham K., Auewarakul P., Yoksan S., Malasit P., Puttikhunt C., Ketloy C., Sittisombut N. Blockade-of-Binding Activities toward Envelope-Associated, Type-Specific Epitopes as a Correlative Marker for Dengue Virus-Neutralizing Antibody. Microbiology spectrum Vol.11 No.4 (2023) , e0091823. doi:10.1128/spectrum.00918-23 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88850
Title
Blockade-of-Binding Activities toward Envelope-Associated, Type-Specific Epitopes as a Correlative Marker for Dengue Virus-Neutralizing Antibody
Author(s)
Author's Affiliation
Siriraj Hospital
Faculty of Medicine, Chiang Mai University
University of Oxford
Faculty of Medicine, Khon Kaen University
Chulabhorn Royal Academy
Khon Kaen University
Thailand National Center for Genetic Engineering and Biotechnology
Institute of Molecular Biosciences, Mahidol University
Nuffield Department of Medicine
Faculty of Medicine, Chulalongkorn University
Faculty of Medicine, Chiang Mai University
University of Oxford
Faculty of Medicine, Khon Kaen University
Chulabhorn Royal Academy
Khon Kaen University
Thailand National Center for Genetic Engineering and Biotechnology
Institute of Molecular Biosciences, Mahidol University
Nuffield Department of Medicine
Faculty of Medicine, Chulalongkorn University
Other Contributor(s)
Abstract
Humans infected with dengue virus (DENV) acquire long-term protection against the infecting serotype, whereas cross-protection against other serotypes is short-lived. Long-term protection induced by low levels of type-specific neutralizing antibodies can be assessed using the virus-neutralizing antibody test. However, this test is laborious and time-consuming. In this study, a blockade-of-binding enzyme-linked immunoassay was developed to assess antibody activity by using a set of neutralizing anti-E monoclonal antibodies and blood samples from dengue virus-infected or -immunized macaques. Diluted blood samples were incubated with plate-bound dengue virus particles before the addition of an enzyme-conjugated antibody specific to the epitope of interest. Based on blocking reference curves constructed using autologous purified antibodies, sample blocking activity was determined as the relative concentration of unconjugated antibody that resulted in the same percent signal reduction. In separate DENV-1-, -2-, -3-, and -4-related sets of samples, moderate to strong correlations of the blocking activity with neutralizing antibody titers were found with the four type-specific antibodies 1F4, 3H5, 8A1, and 5H2, respectively. Significant correlations were observed for single samples taken 1 month after infection as well as samples drawn before and at various time points after infection/immunization. Similar testing using a cross-reactive EDE-1 antibody revealed a moderate correlation between the blocking activity and the neutralizing antibody titer only for the DENV-2-related set. The potential usefulness of the blockade-of-binding activity as a correlative marker of neutralizing antibodies against dengue viruses needs to be validated in humans. IMPORTANCE This study describes a blockade-of-binding assay for the determination of antibodies that recognize a selected set of serotype-specific or group-reactive epitopes in the envelope of dengue virus. By employing blood samples collected from dengue virus-infected or -immunized macaques, moderate to strong correlations of the epitope-blocking activities with the virus-neutralizing antibody titers were observed with serotype-specific blocking activities for each of the four dengue serotypes. This simple, rapid, and less laborious method should be useful for the evaluation of antibody responses to dengue virus infection and may serve as, or be a component of, an in vitro correlate of protection against dengue in the future.