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

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).

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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 -

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 -

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Abstract