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Updated: Feb 14, 2026
07:55
Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
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Monoclonal IgM antibodies mediate potent complement neutralization by targeting cell-derived epitopes on enveloped
Markus H Kainulainen1, Jessica R Harmon1, Éric Bergeron1
1Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Mbio
|February 13, 2026
Summary
Innate immunity, specifically IgM antibodies, can neutralize enveloped viruses like Ebola by targeting host gangliosides. This natural defense mechanism is crucial for understanding viral infection outcomes and immune responses.
Area of Science:
- Immunology
- Virology
- Biochemistry
Background:
- Serum heat treatment is standard for studying adaptive antibody neutralization, removing complement system effects.
- Innate immune responses, though non-specific, can significantly influence viral infection outcomes.
- Observed significant variation in Ebola virus and other enveloped virus neutralization by complement in naïve serum donors.
Purpose of the Study:
- To investigate the mechanism behind the observed variation in virus neutralization by complement in naïve individuals.
- To identify the specific epitope targeted by neutralizing IgM antibodies.
- To understand the role of cell-derived moieties in virus neutralization.
Main Methods:
- Studied complement-mediated neutralization of enveloped viruses, including Ebola virus.
- Isolated and characterized three monoclonal IgM antibodies from neutralization screens.
- Probed antibodies against arrayed glycans to identify the target epitope; used ganglioside synthesis inhibitors.
Main Results:
- Complement activation via the classical pathway, initiated by serum IgM, mediated virus neutralization.
- Neutralizing IgM antibodies targeted the ganglioside GM2.
- Virus propagation with a ganglioside synthesis inhibitor rendered it resistant to anti-GM2 neutralization.
Conclusions:
- Host-derived gangliosides on enveloped viruses can be recognized by potent neutralizing IgM antibodies in immunologically naïve individuals.
- Cellular factors incorporated into viral lipid envelopes can serve as targets for antibody-mediated immune surveillance.
- Findings highlight the importance of cell-derived markers on virions in natural antiviral immunity.
Keywords:
B-cell epitopeEbola virusIgM antibodyantibody specificitybroadly neutralizing antibodiescomplementfalse-positive reactionsgangliosideneutralizing antibodiesMore Related Videos
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