TY - JOUR
T1 - Organoid-based evaluation of SA55 and Pemivibart against evolving SARS-CoV-2 variants
AU - Wan, Zhixin
AU - Zhou, Ying
AU - Jian, Fanchong
AU - Wu, Jiali
AU - Xue, Wei
AU - Chiu, Man Chun
AU - Yu, Yifei
AU - Lan, Qiaoshuai
AU - Zhang, Shuxin
AU - Zhao, Zijun
AU - Zhu, Xiaoxin
AU - Huang, Jingjing
AU - Yang, Yidong
AU - Liu, Yuhong
AU - Meng, Xinjie
AU - Huang, Lin
AU - Gao, Xiang
AU - Chu, Hin
AU - Li, Cun
AU - Cao, Yunlong
AU - Zhou, Jie
N1 - Publisher Copyright:
© 2026 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.
PY - 2026
Y1 - 2026
N2 - Pemivibart, a class 1/4 monoclonal antibody (mAb), is currently the only FDA-authorized SARS-CoV-2 mAb under an Emergency Use Authorization (EUA) in clinical use. The emergence of subvariants, including KP.3.1.1 and XFG, raises concerns about antibody efficacy. SA55, a fully human class 1/4 mAb, is currently under clinical trial, including a nasal spray formulation. Using the well-validated organoid-based neutralization assays, we compared the potency and breadth of Pemivibart and SA55. Our results demonstrated a significant decrease in Pemivibart’s activity against KP.3.1.1 and XFG, with an approximately 80-fold increase in IC50 relative to the ancestral strain. Given KP.3.1.1’s strong reliance on the TMPRSS2 pathway for cell entry, we further demonstrated that combinational treatment with Pemivibart and the broad-spectrum S2 antibody results in potent neutralization. Notably, SA55 maintained potent neutralization (IC50 ≤ 40 ng/mL) across all tested variants. Topical administration, which models nasal spray, dramatically suppressed viral replication of BA.5.2 and XFG in organoid models. Our findings evidence the high potency of SA55, supporting its potential for clinical application against emerging SARS-CoV-2 variants.
AB - Pemivibart, a class 1/4 monoclonal antibody (mAb), is currently the only FDA-authorized SARS-CoV-2 mAb under an Emergency Use Authorization (EUA) in clinical use. The emergence of subvariants, including KP.3.1.1 and XFG, raises concerns about antibody efficacy. SA55, a fully human class 1/4 mAb, is currently under clinical trial, including a nasal spray formulation. Using the well-validated organoid-based neutralization assays, we compared the potency and breadth of Pemivibart and SA55. Our results demonstrated a significant decrease in Pemivibart’s activity against KP.3.1.1 and XFG, with an approximately 80-fold increase in IC50 relative to the ancestral strain. Given KP.3.1.1’s strong reliance on the TMPRSS2 pathway for cell entry, we further demonstrated that combinational treatment with Pemivibart and the broad-spectrum S2 antibody results in potent neutralization. Notably, SA55 maintained potent neutralization (IC50 ≤ 40 ng/mL) across all tested variants. Topical administration, which models nasal spray, dramatically suppressed viral replication of BA.5.2 and XFG in organoid models. Our findings evidence the high potency of SA55, supporting its potential for clinical application against emerging SARS-CoV-2 variants.
KW - Pemivibart
KW - SA55
KW - SARS-CoV-2
KW - neutralization assasys
KW - organoid
UR - https://www.scopus.com/pages/publications/105047170976
U2 - 10.1080/22221751.2026.2713323
DO - 10.1080/22221751.2026.2713323
M3 - Article
C2 - 42545256
AN - SCOPUS:105047170976
SN - 2222-1751
VL - 15
JO - Emerging Microbes and Infections
JF - Emerging Microbes and Infections
IS - 1
M1 - 2713323
ER -