Publication: A mouse monoclonal antibody against dengue virus type 1 mochizuki strain targeting envelope protein domain II and displaying strongly neutralizing but not enhancing activity
Issued Date
2013-12-01
Resource Type
ISSN
10985514
0022538X
0022538X
Other identifier(s)
2-s2.0-84887157759
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Virology. Vol.87, No.23 (2013), 12828-12837
Suggested Citation
Atsushi Yamanaka, Tomohiro Kotaki, Eiji Konishi A mouse monoclonal antibody against dengue virus type 1 mochizuki strain targeting envelope protein domain II and displaying strongly neutralizing but not enhancing activity. Journal of Virology. Vol.87, No.23 (2013), 12828-12837. doi:10.1128/JVI.01874-13 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/31822
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
A mouse monoclonal antibody against dengue virus type 1 mochizuki strain targeting envelope protein domain II and displaying strongly neutralizing but not enhancing activity
Author(s)
Other Contributor(s)
Abstract
Dengue fever and its more severe form, dengue hemorrhagic fever, are major global concerns. Infection-enhancing antibodies are major factors hypothetically contributing to increased disease severity. In this study, we generated 26 monoclonal antibodies (MAbs) against the dengue virus type 1 Mochizuki strain. We selected this strain because a relatively large number of unique and rare amino acids were found on its envelope protein. Although most MAbs showing neutralizing activities exhibited enhancing activities at subneutralizing doses, one MAb (D1-IV-7F4 [7F4]) displayed neutralizing activities without showing enhancing activities at lower concentrations. In contrast, another MAb (D1-V-3H12 [3H12]) exhibited only enhancing activities, which were suppressed by pretreatment of cells with anti-FcγRIIa. Although antibody engineering revealed that antibody subclass significantly affected 7F4 (IgG3) and 3H12 (IgG1) activities, neutralizing/enhancing activities were also dependent on the epitope targeted by the antibody. 7F4 recognized an epitope on the envelope protein containing E118 (domain II) and had a neutralizing activity 10- to 1,000-fold stronger than the neutralizing activity of previously reported human or humanized neutralizing MAbs targeting domain I and/or domain II. An epitope-blocking enzyme-linked immunosorbent assay (ELISA) indicated that a dengue virus-immune population possessed antibodies sharing an epitope with 7F4. Our results demonstrating induction of these antibody species (7F4 and 3H12) in Mochizuki-immunized mice may have implications for dengue vaccine strategies designed to minimize induction of enhancing antibodies in vaccinated humans. © 2013, American Society for Microbiology.