Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages

Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages Publisher Pubmed

Marcotte H¹ ; Cao Y^{2, 3} ; Zuo F¹ ; Simonelli L⁴ ; Sammartino JC⁵ ; Pedotti M⁴ ; Sun R¹ ; Cassaniti I⁵ ; Hagbom M⁶ ; Piralla A⁵ ; Yang J⁷ ; Du L¹ ; Percivalle E⁵ ; Bertoglio F⁸ Show All Authors

Marcotte H¹
Cao Y^{2, 3}
Zuo F¹
Simonelli L⁴
Sammartino JC⁵
Pedotti M⁴
Sun R¹
Cassaniti I⁵
Hagbom M⁶
Piralla A⁵
Yang J⁷
Du L¹
Percivalle E⁵
Bertoglio F⁸
Schubert M⁸
Abolhassani H¹
Sherina N¹
Guerra C⁴
Borte S^{9, 10}
Rezaei N¹¹
Kumagaibraesch M¹²
Xue Y¹³
Su C¹⁴
Yan Q¹⁵
He P¹⁵
Gronwall C¹⁶
Klareskog L^{16, 17}
Calzolai L¹⁸
Cavalli A⁴
Wang Q¹⁹
Robbiani DF⁴
Hust M⁸
Shi Z²⁰
Feng L¹⁵
Svensson L^{6, 21}
Chen L²²
Bao L^{23, 24}
Baldanti F^{5, 25}
Xiao J^{2, 14}
Qin C^{23, 24}
Hammarstrom L¹
Yang X⁷
Varani L⁴
Xie XS^{2, 3}
Panhammarstrom Q¹

Show Affiliations

1. Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, 17165, Sweden
2. Changping Laboratory, Beijing, 102206, China
3. School of Life Sciences, Biomedical Pioneering Innovation Center, Peking University, Beijing, 100871, China
4. Institute for Research in Biomedicine, Universita della Svizzera italiana, Bellinzona, 6500, Switzerland
5. Microbiology and Virology Department, Fondazione Istituto di ricovero e cura a carattere scientifico (IRCCS) Policlinico San Matteo, Pavia, 27100, Italy
6. Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linkoping University, Linkoping, 58185, Sweden
7. Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650023, China
8. Department of Medical Biotechnology, Institute of Biochemistry Biotechnology and Bioinformatics, Technische Universitat Braunschweig, Braunschweig, 38106, Germany
9. Department of Laboratory Medicine, Hospital St. Georg, Leipzig, 04129, Germany
10. ImmunoDeficiencyCenter Leipzig, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiency Diseases, Hospital St. Georg, Leipzig, 04129, Germany
11. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, 14194, Iran
12. Division of Transplantation Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, 14186, Sweden
13. Department of Immunology, Peking University Health Science Center, Beijing, 100191, China
14. State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China
15. State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China
16. Division of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, 17176, Sweden
17. Rheumatology Unit, Karolinska University Hospital, Stockholm, 17176, Sweden
18. European Commission, Joint Research Centre, Ispra, 21027, Italy
19. 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, Shanghai, 200032, China
20. State Key laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, 430071, China
21. Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Stockholm, 17177, Sweden
22. Guangzhou Laboratory, Guangzhou, 510005, China
23. 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, China
24. National Center of Technology Innovation for Animal Model, Beijing, 102206, China
25. Department of Clinical Surgical Diagnostic and Paediatric Sciences, University of Pavia, Pavia, 27100, Italy

Source: Proceedings of the National Academy of Sciences of the United States of America Published:2024

Abstract

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. © 2024 the Author(s).

2. Epitope Mapping of Neutralising Anti-Sars-Cov-2 Monoclonal Antibodies: Implications for Immunotherapy and Vaccine Design, Reviews in Medical Virology (2022)

3. Preclinical Assessment of a Recombinant Rbd-Fc Fusion Protein As Sars-Cov-2 Candidate Vaccine, European Journal of Microbiology and Immunology (2024)

4. Comparison of Immune Response Between Sars, Mers, and Covid-19 Infection, Perspective on Vaccine Design and Development, BioMed Research International (2021)

5. Heterologous Inactivated Virus/Mrna Vaccination Response to Bf.7, Bq.1.1, and Xbb.1, The Lancet Regional Health - Western Pacific (2023)

Experts (# of related papers)

View all Related Experts

Forough Golsaz Shirazi (2)

Mohammad Mehdi Amiri (2)

Style	Citing Format
MLA	Marcotte H, et al.. "Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages." Proceedings of the National Academy of Sciences of the United States of America, vol. 121, no. 3, 2024, pp. -.
APA	Marcotte H, Cao Y, Zuo F, Simonelli L, Sammartino JC, Pedotti M, Sun R, Cassaniti I, Hagbom M, Piralla A, Yang J, Du L, Percivalle E, Bertoglio F, Schubert M, Abolhassani H, Sherina N, Guerra C, Borte S, ... Panhammarstrom Q (2024). Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages. Proceedings of the National Academy of Sciences of the United States of America, 121(3), -.
Chicago	Marcotte H, Cao Y, Zuo F, Simonelli L, Sammartino JC, Pedotti M, Sun R, et al.. "Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages." Proceedings of the National Academy of Sciences of the United States of America 121, no. 3 (2024): -.
Harvard	Marcotte H et al. (2024) 'Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages', Proceedings of the National Academy of Sciences of the United States of America, 121(3), pp. -.
Vancouver	Marcotte H, Cao Y, Zuo F, Simonelli L, Sammartino JC, Pedotti M, et al.. Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages. Proceedings of the National Academy of Sciences of the United States of America. 2024;121(3):-.
BibTex	@article{ author = {Marcotte H and Cao Y and Zuo F and Simonelli L and Sammartino JC and Pedotti M and Sun R and Cassaniti I and Hagbom M and Piralla A and Yang J and Du L and Percivalle E and Bertoglio F and Schubert M and Abolhassani H and Sherina N and Guerra C and Borte S and Rezaei N and Kumagaibraesch M and Xue Y and Su C and Yan Q and He P and Gronwall C and Klareskog L and Calzolai L and Cavalli A and Wang Q and Robbiani DF and Hust M and Shi Z and Feng L and Svensson L and Chen L and Bao L and Baldanti F and Xiao J and Qin C and Hammarstrom L and Yang X and Varani L and Xie XS and Panhammarstrom Q}, title = {Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {3}, pages = {-}, year = {2024} }
RIS	TY - JOUR AU - Marcotte H AU - Cao Y AU - Zuo F AU - Simonelli L AU - Sammartino JC AU - Pedotti M AU - Sun R AU - Cassaniti I AU - Hagbom M AU - Piralla A AU - Yang J AU - Du L AU - Percivalle E AU - Bertoglio F AU - Schubert M AU - Abolhassani H AU - Sherina N AU - Guerra C AU - Borte S AU - Rezaei N AU - Kumagaibraesch M AU - Xue Y AU - Su C AU - Yan Q AU - He P AU - Gronwall C AU - Klareskog L AU - Calzolai L AU - Cavalli A AU - Wang Q AU - Robbiani DF AU - Hust M AU - Shi Z AU - Feng L AU - Svensson L AU - Chen L AU - Bao L AU - Baldanti F AU - Xiao J AU - Qin C AU - Hammarstrom L AU - Yang X AU - Varani L AU - Xie XS AU - Panhammarstrom Q TI - Conversion of Monoclonal Igg to Dimeric and Secretory Iga Restores Neutralizing Ability and Prevents Infection of Omicron Lineages JO - Proceedings of the National Academy of Sciences of the United States of America VL - 121 IS - 3 SP - EP - PY - 2024 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract