Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages

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Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages

Marcotte, Harold (author): Karolinska Institutet,Karolinska Inst, Sweden

Cao, Yunlong (author): Changping Lab, Peoples R China; Peking Univ, Peoples R China

Zuo, Fanglei (author): Karolinska Inst, Sweden

Simonelli, Luca (author): Univ Svizzera italiana, Switzerland

Sammartino, Jose Camilla (author): Fdn Ist Ricovero & Cura Carattere Sci IRCCS Policl, Italy

Pedotti, Mattia (author): Univ Svizzera italiana, Switzerland

Sun, Rui (author): Karolinska Institutet,Karolinska Inst, Sweden

Cassaniti, Irene (author): Fdn Ist Ricovero & Cura Carattere Sci IRCCS Policl, Italy

Hagbom, Marie (author): Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten

Piralla, Antonio (author): Fdn Ist Ricovero & Cura Carattere Sci IRCCS Policl, Italy

Yang, Jinxuan (author): Chinese Acad Sci, Peoples R China

Du, Likun (author): Karolinska Institutet,Karolinska Inst, Sweden

Percivalle, Elena (author): Fdn Ist Ricovero & Cura Carattere Sci IRCCS Policl, Italy

Bertoglio, Federico (author): Tech Univ Carolo Wilhelmina Braunschweig, Germany

Schubert, Maren (author): Tech Univ Carolo Wilhelmina Braunschweig, Germany

Abolhassani, Hassan (author): Karolinska Institutet,Karolinska Inst, Sweden

Sherina, Natalia (author): Karolinska Institutet,Karolinska Inst, Sweden

Guerra, Concetta (author): Univ Svizzera italiana, Switzerland

Borte, Stephan (author): Hosp St Georg, Germany; Hosp St Georg, Germany

Rezaei, Nima (author): Univ Tehran Med Sci, Iran

Kumagai-Braesch, Makiko (author): Karolinska Institutet,Karolinska Inst, Sweden

Xue, Yintong (author): Peking Univ, Peoples R China

Su, Chen (author): Peking Univ, Peoples R China

Yan, Qihong (author): Karolinska Institutet,Chinese Acad Sci, Peoples R China,Karolinska Inst, Sweden

He, Ping (author): Chinese Acad Sci, Peoples R China

Groenwall, Caroline (author): Karolinska Institutet,Karolinska Univ Hosp, Sweden

Klareskog, Lars (author): Karolinska Institutet,Karolinska Univ Hosp, Sweden

Calzolai, Luigi (author): European Commiss, Italy

Cavalli, Andrea (author): Univ Svizzera italiana, Switzerland

Wang, Qiao (author): Fudan Univ, Peoples R China

Robbiani, Davide F. (author): Univ Svizzera italiana, Switzerland

Hust, Michael (author): Tech Univ Carolo Wilhelmina Braunschweig, Germany

Shi, Zhengli (author): Chinese Acad Sci, Peoples R China

Feng, Liqiang (author): Chinese Acad Sci, Peoples R China

Svensson, Lennart (author): Karolinska Institutet,Linköpings universitet,Avdelningen för molekylär medicin och virologi,Medicinska fakulteten,Karolinska Inst, Sweden

Chen, Ling (author): Guangzhou Lab, Peoples R China

Bao, Linlin (author): Inst Lab Anim Sci, Peoples R China; Peking Union Med Coll, Peoples R China; Natl Ctr Technol Innovat Anim Model, Peoples R China

Baldanti, Fausto (author): Fdn Ist Ricovero & Cura Carattere Sci IRCCS Policl, Italy; Univ Pavia, Italy

Xiao, Junyu (author): Changping Lab, Peoples R China

Qin, Chuan (author): Inst Lab Anim Sci, Peoples R China; Peking Union Med Coll, Peoples R China; Natl Ctr Technol Innovat Anim Model, Peoples R China

Hammarstrom, Lennart (author): Karolinska Institutet,Karolinska Inst, Sweden

Yang, Xinglou (author): Chinese Acad Sci, Peoples R China

Varani, Luca (author): Univ Svizzera italiana, Switzerland

Xie, Xiaoliang Sunney (author): Changping Lab, Peoples R China; Peking Univ, Peoples R China

Pan-Hammarstrom, Qiang (author): Karolinska Inst, Sweden

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NATL ACAD SCIENCES, 2024
2024
English.
In: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 121:3

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; http://kipublication...; show less...

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Abstract Subject headings

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previ- ously 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 suffi- ciently boost the mucosal secretory IgA response in uninfected individuals, particu- larly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgAl 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 antibod- ies, dimeric and secretory IgAl antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgAl 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 secre- tory IgA delivered by nasal administration may potentially be exploited for the treatment Iand prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.

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By the author/editor: Marcotte, Harold; Cao, Yunlong; Zuo, Fanglei; Simonelli, Luca; Sammartino, Jose ...; Pedotti, Mattia; show more...; Sun, Rui; Cassaniti, Irene; Hagbom, Marie; Piralla, Antonio; Yang, Jinxuan; Du, Likun; Percivalle, Elen ...; Bertoglio, Feder ...; Schubert, Maren; Abolhassani, Has ...; Sherina, Natalia; Guerra, Concetta; Borte, Stephan; Rezaei, Nima; Kumagai-Braesch, ...; Xue, Yintong; Su, Chen; Yan, Qihong; He, Ping; Groenwall, Carol ...; Klareskog, Lars; Calzolai, Luigi; Cavalli, Andrea; Wang, Qiao; Robbiani, Davide ...; Hust, Michael; Shi, Zhengli; Feng, Liqiang; Svensson, Lennar ...; Chen, Ling; Bao, Linlin; Baldanti, Fausto; Xiao, Junyu; Qin, Chuan; Hammarstrom, Len ...; Yang, Xinglou; Varani, Luca; Xie, Xiaoliang S ...; Pan-Hammarstrom, ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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By the university: Linköping University; Karolinska Institutet

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Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages

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