Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents infection of Omicron lineages.
Autor: | Marcotte H; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden., Cao Y; Changping Laboratory, Beijing 102206, People's Republic of China.; School of Life Sciences, Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, People's Republic of China., Zuo F; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden., Simonelli L; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Sammartino JC; Microbiology and Virology Department, Fondazione Istituto di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia 27100, Italy., Pedotti M; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Sun R; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden., Cassaniti I; Microbiology and Virology Department, Fondazione Istituto di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia 27100, Italy., Hagbom M; Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden., Piralla A; Microbiology and Virology Department, Fondazione Istituto di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia 27100, Italy., Yang J; Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650023, People's Republic of China., Du L; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden., Percivalle E; Microbiology and Virology Department, Fondazione Istituto di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia 27100, Italy., Bertoglio F; Department of Medical Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig 38106, Germany., Schubert M; Department of Medical Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig 38106, Germany., Abolhassani H; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden., Sherina N; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden., Guerra C; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Borte S; Department of Laboratory Medicine, Hospital St. Georg, Leipzig 04129, Germany.; ImmunoDeficiencyCenter Leipzig, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency Diseases, Hospital St. Georg, Leipzig 04129, Germany., Rezaei N; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran 14194, Iran., Kumagai-Braesch M; Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm 14186, Sweden., Xue Y; Department of Immunology, Peking University Health Science Center, Beijing 100191, People's Republic of China., Su C; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, People's Republic of China., Yan Q; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, People's Republic of China., He P; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, People's Republic of China., Grönwall C; Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm 17176, Sweden., Klareskog L; Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm 17176, Sweden.; Rheumatology Unit, Karolinska University Hospital, Stockholm 17176, Sweden., Calzolai L; European Commission, Joint Research Centre, Ispra 21027, Italy., Cavalli A; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Wang Q; Key Laboratory of Medical Molecular Virology (Ministry of Education/National Health Commission/Chinese Academy of Medical Sciences), Shanghai Institute of Infectious Disease and Biosecurity, School of Basic Medical Sciences, Fudan University, 200032 Shanghai 200032, People's Republic of China., Robbiani DF; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Hust M; Department of Medical Biotechnology, Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig 38106, Germany., Shi Z; State Key laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, People's Republic of China., Feng L; State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, People's Republic of China., Svensson L; Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden.; Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Stockholm 17177, Sweden., Chen L; Guangzhou Laboratory, Guangzhou 510005, People's Republic of China., Bao L; Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, National Health Commission Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, People's Republic of China.; National Center of Technology Innovation for Animal Model, Beijing 102206, People's Republic of China., Baldanti F; Microbiology and Virology Department, Fondazione Istituto di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia 27100, Italy.; Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia 27100, Italy., Xiao J; Changping Laboratory, Beijing 102206, People's Republic of China.; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, People's Republic of China., Qin C; Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, National Health Commission Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100021, People's Republic of China.; National Center of Technology Innovation for Animal Model, Beijing 102206, People's Republic of China., Hammarström L; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden., Yang X; Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650023, People's Republic of China., Varani L; Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona 6500, Switzerland., Xie XS; Changping Laboratory, Beijing 102206, People's Republic of China.; School of Life Sciences, Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, People's Republic of China., Pan-Hammarström Q; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, Sweden. |
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Jazyk: | angličtina |
Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jan 16; Vol. 121 (3), pp. e2315354120. Date of Electronic Publication: 2024 Jan 09. |
DOI: | 10.1073/pnas.2315354120 |
Abstrakt: | The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot sufficiently boost the mucosal secretory IgA response in uninfected individuals, particularly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgA1 antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibodies, dimeric and secretory IgA1 antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgA1 form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secretory IgA delivered by nasal administration may potentially be exploited for the treatment and prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs. Competing Interests: Competing interests statement:Y.C. and X.S.X. are listed as inventors on a patent on DXP-604 antibody (PCT/CN2021/093305) for Peking University. H.M., Y.C., L.H., X.S.X., and Q.P.-H. have filed a patent on DXP-604 IgA antibodies. All other authors declare that they have no competing interests. |
Databáze: | MEDLINE |
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