Dissecting antibody-dependent enhancement modulation by Fc-modified cross-neutralizing human monoclonal antibody
Our novel Fc-modified antibody LALA-B3B9 (Leu234Ala/Leu235Ala mutations), exhibited neutralizing activity against all dengue virus serotypes without triggering ADE activity at any antibody concentration. This outcome was similar to that observed with the previously developed Fc-modified N297Q-B3B9 antibody (N297Q mutation). We further evaluated the effect of complement protein on the enhancing and neutralizing activities of our Fc-modified antibodies. The results showed that LALA-B3B9 and N297Q-B3B9 HuMAbs were complement-independent, meaning that the reduced binding between complement protein (C1q) and the Fc portion of the antibody left the neutralizing and enhancing activities unchanged. Additionally, both LALA-B3B9 and N297Q-B3B9 HuMAbs demonstrated the suppression-of-enhancement activity in K562 cells induced by human anti-DENV serum antibodies. Overall, this study highlights the main advantages of our EDII-specific HuMAbs in inhibiting <i>in vitro</i> ADE, indicating that they are promising candidates for future dengue treatment.
Authors
- Pannamthip Pitaksajjakul (ORCID: https://orcid.org/0000-0003-2088-6999)
- Rochanawan Sootichote
- Pongrama Ramasoota (ORCID: https://orcid.org/0000-0003-3097-5733)
- Sujitra Keadsanti
- Tadahiro Sasaki (ORCID: https://orcid.org/0000-0003-3473-3803)
- Wilarat Puangmanee
- Atsushi Yamanaka (ORCID: https://orcid.org/0000-0002-2757-2792)
- Subenya Injampa
- Surachet Benjathummarak (ORCID: https://orcid.org/0000-0003-2959-6728)
Institutions
- Mahidol University (TH)
- Mahidol Oxford Tropical Medicine Research Unit (TH)
- King Mongkut's Institute of Technology Ladkrabang (TH)
- The University of Osaka (JP)
Publication Details
- Journal
- PeerJ
- Published
- 2025-11-19
- DOI
- https://doi.org/10.7717/peerj.20329
- Primary Topic
- Monoclonal and Polyclonal Antibodies Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00