Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement
To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups who...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Antibodies |
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| Online Access: | https://www.mdpi.com/2073-4468/12/2/36 |
| _version_ | 1797596405693415424 |
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| author | Zenjiro Sampei Christine Xing’er Koo Frannie Jiuyi Teo Ying Xiu Toh Taku Fukuzawa Siok Wan Gan Takeru Nambu Adrian Ho Kiyofumi Honda Tomoyuki Igawa Fariyal Ahmed Cheng-I Wang Katja Fink Junichi Nezu |
| author_facet | Zenjiro Sampei Christine Xing’er Koo Frannie Jiuyi Teo Ying Xiu Toh Taku Fukuzawa Siok Wan Gan Takeru Nambu Adrian Ho Kiyofumi Honda Tomoyuki Igawa Fariyal Ahmed Cheng-I Wang Katja Fink Junichi Nezu |
| author_sort | Zenjiro Sampei |
| collection | DOAJ |
| description | To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses. |
| first_indexed | 2024-03-11T02:50:56Z |
| format | Article |
| id | doaj.art-a2953071e1654c75af8815c87546bdba |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-03-11T02:50:56Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-a2953071e1654c75af8815c87546bdba2023-11-18T09:01:54ZengMDPI AGAntibodies2073-44682023-05-011223610.3390/antib12020036Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent EnhancementZenjiro Sampei0Christine Xing’er Koo1Frannie Jiuyi Teo2Ying Xiu Toh3Taku Fukuzawa4Siok Wan Gan5Takeru Nambu6Adrian Ho7Kiyofumi Honda8Tomoyuki Igawa9Fariyal Ahmed10Cheng-I Wang11Katja Fink12Junichi Nezu13Chugai Pharmaceutical Co., Ltd., Yokohama 244-8602, JapanChugai Pharmabody Research Pte. Ltd., Singapore 138623, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, SingaporeChugai Pharmaceutical Co., Ltd., Yokohama 244-8602, JapanChugai Pharmabody Research Pte. Ltd., Singapore 138623, SingaporeChugai Pharmaceutical Co., Ltd., Yokohama 244-8602, JapanChugai Pharmabody Research Pte. Ltd., Singapore 138623, SingaporeChugai Pharmaceutical Co., Ltd., Yokohama 244-8602, JapanChugai Pharmaceutical Co., Ltd., Yokohama 244-8602, JapanSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, SingaporeSingapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, SingaporeChugai Pharmaceutical Co., Ltd., Yokohama 244-8602, JapanTo combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.https://www.mdpi.com/2073-4468/12/2/36antibody engineeringFc engineeringanti-virus antibodycomplementC1qFcγ receptor |
| spellingShingle | Zenjiro Sampei Christine Xing’er Koo Frannie Jiuyi Teo Ying Xiu Toh Taku Fukuzawa Siok Wan Gan Takeru Nambu Adrian Ho Kiyofumi Honda Tomoyuki Igawa Fariyal Ahmed Cheng-I Wang Katja Fink Junichi Nezu Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement Antibodies antibody engineering Fc engineering anti-virus antibody complement C1q Fcγ receptor |
| title | Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement |
| title_full | Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement |
| title_fullStr | Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement |
| title_full_unstemmed | Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement |
| title_short | Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement |
| title_sort | complement activation by an anti dengue zika antibody with impaired fcγ receptor binding provides strong efficacy and abrogates risk of antibody dependent enhancement |
| topic | antibody engineering Fc engineering anti-virus antibody complement C1q Fcγ receptor |
| url | https://www.mdpi.com/2073-4468/12/2/36 |
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