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Updated: Jan 10, 2026
04:47
A Method to Assess Fc-mediated Effector Functions Induced by Influenza Hemagglutinin Specific Antibodies
Published on: February 23, 2018
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Dissecting antibody-dependent enhancement modulation by Fc-modified cross-neutralizing human monoclonal antibody
Subenya Injampa1, Surachet Benjathummarak2, Sujitra Keadsanti2
1Faculty of Medicine, King Mongkut's Institute of Technology, Ladkrabang, Bangkok, Thailand.
Peerj
|November 24, 2025
Summary
Researchers developed a novel human monoclonal antibody, LALA-B3B9, that neutralizes all four dengue virus serotypes without causing antibody-dependent enhancement (ADE). This antibody shows promise for dengue treatment by inhibiting ADE in vitro.
Area of Science:
- Immunology
- Virology
- Therapeutic antibody development
Background:
- Dengue virus (DENV) infection poses a significant global health threat, with secondary infections potentially worsening due to antibody-dependent enhancement (ADE).
- ADE involves sub-neutralizing antibodies increasing viral infection severity by activating immune cells and complement.
- Current therapeutic options, especially fully human monoclonal antibodies, for dengue are lacking.
Purpose of the Study:
- To develop and characterize a novel human monoclonal antibody (HuMAb) capable of neutralizing all four DENV serotypes without inducing ADE.
- To evaluate the therapeutic potential of engineered HuMAbs, specifically LALA-B3B9, in preclinical models of dengue.
- To assess the impact of Fc modifications on antibody effector functions and therapeutic efficacy.
Main Methods:
- Generation of LALA-mutated human monoclonal antibody clone B3B9 (LALA-B3B9 HuMAb).
- Assessment of neutralizing and ADE activities using ADE assays with varying antibody concentrations and complement proteins.
- Evaluation of therapeutic efficacy via in vitro suppression-of-enhancement assays using K562 cells and patient-derived anti-DENV antibodies.
Main Results:
- The LALA-B3B9 HuMAb demonstrated potent neutralizing activity against all four DENV serotypes without inducing ADE.
- Fc-modified antibodies (LALA-B3B9 and N297Q-B3B9) showed complement-independent activity, with reduced C1q binding not affecting neutralization or enhancement.
- Both LALA-B3B9 and N297Q-B3B9 HuMAbs effectively suppressed ADE induced by human anti-DENV serum antibodies in vitro.
Conclusions:
- Fc-modified human monoclonal antibodies, such as LALA-B3B9, are effective in neutralizing DENV and inhibiting ADE.
- These antibodies offer a promising strategy for passive immunotherapy against dengue, potentially overcoming ADE-related complications.
- Further development of these engineered antibodies could lead to novel therapeutic interventions for dengue fever.
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