Synergistic Interactions of Anti-NS1 Monoclonal Antibodies Protect Passively Immunized Mice from Lethal Challenge with Dengue 2 Virus
Erik A. Henchala b, Laraine S. Henchalb, Jacob J. Schlesingerc
- aDepartment of Virology, U.S. Army Medical Component, Armed Forces Research Institute of the Medical Sciences, Bangkok, Thailand
- bDepartment of Virology, U.S. Army Medical Component, Armed Forces Research Institute of the Medical Sciences, 315/6 Rajavithi Road, Bangkok 10400, Thailand
- cDepartment of Medicine, Rochester General Hospital and the University of Rochester School of Medicine and Dentistry, Rochester, New York 14621, U.S.A
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Abstract
Non-neutralizing, serotype-specific anti-NS1 monoclonal antibodies partially protected passively immunized mice from lethal dengue 2 virus intracerebral challenge. There was no apparent correlation between complement-fixing activity and protective capacity among individual anti-NS1 monoclonal antibodies. Immunization with specific combinations of non-protective or partially protective antibodies resulted in prolonged survival or reduced mortality. Solid protection, equal to that achieved after immunization with neutralizing polyclonal antibody, was achieved only with an antibody pair which individually fixed complement to high titre with homologous virus. Some groups of mice had increased morbidity after immunization with combinations of protective monoclonal antibodies that bind to overlapping epitopes. These results may affect the design of recombinant dengue vaccines which may require the inclusion of serotype-specific antigenic domains.
TL;DRNon-neutralizing, serotype-specific anti-NS1 monoclonal antibodies partially protected passively immunized mice from lethal dengue 2 virus intracerebral challenge and some groups of mice had increased morbidity after immunization with combinations of protective monoconal antibodies that bind to overlapping epitopes. (Semantic Scholar)