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Updated: Aug 8, 2025
Generation of Escape Variants of Neutralizing Influenza Virus Monoclonal Antibodies
Published on: August 29, 2017
Potently neutralizing human mAbs against the zoonotic pararubulavirus Sosuga virus
Helen M Parrington1, Nurgun Kose2, Erica Armstrong2
1Department of Pathology, Microbiology and Immunology.
Abstract:
Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human mAbs from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated 6 mAbs recognizing the functional attachment protein hemagglutinin-neuraminidase (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all targeted the globular head of the HN protein and could be organized into 4 competition-binding groups that exhibited epitope diversity. The anti-F mAbs can be divided into pre- or postfusion conformation-specific categories and further into 8 competition-binding groups. The only Ab in the panel that did not display neutralization activity was the single postfusion-specific anti-F mAb. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in 1 of the HN competition-binding groups possessing ultrapotent (<1 ng/mL) half-maximal inhibitory virus neutralization values. These findings provide insight into the molecular basis for human Ab recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization.
Insights
Researchers identified potent human monoclonal antibodies (mAbs) targeting the Sosuga virus (SOSV) hemagglutinin-neuraminidase (HN) and fusion (F) proteins. These antibodies demonstrate significant neutralization capabilities, offering insights for SOSV therapeutic development.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Sosuga virus (SOSV) is an emerging paramyxovirus with limited research on its pathogenesis and immunity.
- No specific therapeutics or vaccines are currently available for SOSV infections.
- Understanding the human immune response to SOSV is crucial for developing countermeasures.
Purpose of the Study:
- To discover and characterize human monoclonal antibodies (mAbs) from a survivor of SOSV infection.
- To investigate the neutralizing potential of these mAbs against SOSV.
- To elucidate the epitope targets on SOSV surface proteins (HN and F) recognized by human antibodies.
Main Methods:
- Isolation of memory B cells from the sole known human survivor of SOSV infection.
- Generation and characterization of monoclonal antibodies (mAbs) against SOSV hemagglutinin-neuraminidase (HN) and fusion (F) proteins.
- Epitope mapping and competition-binding assays to determine antibody binding sites.
- Viral neutralization assays to assess the functional activity of isolated mAbs.
Main Results:
- Successfully isolated 6 anti-HN and 18 anti-F human mAbs.
- Anti-HN mAbs targeted the globular head, showing epitope diversity across 4 groups.
- Anti-F mAbs recognized pre- or postfusion conformations, categorized into 8 groups.
- Most anti-HN mAbs exhibited potent virus neutralization, with some achieving ultrapotent activity (<1 ng/mL IC50).
- A single postfusion-specific anti-F mAb lacked neutralization activity.
Conclusions:
- Human memory B cells from an SOSV survivor can yield potent neutralizing antibodies.
- The hemagglutinin-neuraminidase (HN) protein is a primary target for highly effective neutralizing antibodies against SOSV.
- Findings provide a molecular basis for understanding paramyxovirus antibody recognition and neutralization, informing future therapeutic strategies.
