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
	Marcotte, H; Cao, YL; Zuo, FL; Simonelli, L; Sammartino, JC; Pedotti, M; Sun, R; Cassaniti, I; Hagbom, M; Piralla, A; Yang, JX; Du, LK; Percivalle, E; Bertoglio, F; Schubert, M; Abolhassani, H; Sherina, N; Guerra, C; Borte, S; Rezaei, N; Kumagai-Braesch, M; Xue, YT; Su, C; Yan, QH; He, P; Groenwall, C; Klareskog, L; Calzolai, L; Cavalli, A; Wang, Q; Robbiani, DF; Hust, M; Shi, ZL; Feng, LQ; Svensson, L; Chen, L; Bao, LL; Baldanti, F; Xiao, JY; Qin, C; Hammarström, L; Yang, XL; Varani, L; Xie, XS; Pan-Hammarström, Q
	2024
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN	0027-8424
卷号	121 期号:3
摘要	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.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14217
专题	科研部门_疫源动物病毒（杨兴娄）
推荐引用方式 GB/T 7714	Marcotte, H,Cao, YL,Zuo, FL,et al. Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2024,121(3).
APA	Marcotte, H.,Cao, YL.,Zuo, FL.,Simonelli, L.,Sammartino, JC.,...&Pan-Hammarström, 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).
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 121.3(2024).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2024080130.pdf（7103KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文