A first-in-human clinical study of an intranasal spray of a cocktail containing two synergetic antibodies neutralizes Omicron BA.4/5
Xinghai Zhang, Feiyang Luo, Huajun Zhang, Hangtian Guo, Junhui Zhou, Tingting Li, Shaohong Chen, Shuyi Song, Meiying Shen, Yan Wu, Yan Gao, Xiaojian Han, Yingming Wang, Chao Hu, Xiaodong Zhao, Huilin Guo, Dazhi Zhang, Yuchi Lu, Wei Wang, Kai Wang, Ni Tang, Tengchuan Jin, Menglu Ding, Shuhui Luo, Cuicui Lin, Tingting Lu, Bingxia Lu, Yang Tian, Chengyong Yang, Guofeng Cheng, Haitao Yang, Aishun Jin, Xiaoyun Ji, Rui Gong, Sandra Chiu, Ailong Huang
doi:10.1101/2023.03.17.23287398
All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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'abstract': '<jats:title>Abstract</jats:title><jats:p>Neutralizing monoclonal antibodies (NAbs) with '
'prophylactic and therapeutic efficacy have demonstrated fundamental importance in the control '
'of SARS-CoV-2 transmission. However, their wide application has been largely limited by high '
'cost and inconvenience in administration. Here, we developed an intranasal spray containing '
'two synergetic human NAbs that could broadly neutralize the emerging Omicron variants in '
'vitro. A unique synergetic neutralizing mechanism was identified that the two NAbs bound to '
'exclusive epitopes on the RBD and structurally compensate each other in blocking the '
'Spike-ACE2 interaction. Importantly, when given at low dosages for three consecutive days '
'through the intranasal mucosal route, this cocktail showed significant improvement in the '
'emergency preventive and therapeutic effects in hamsters challenged with authentic Omicron '
'BA.1. Further, we performed an investigator-initiated trail in healthy volunteers '
'(ChiCTR2200066525) to study the safety and pharmacokinetics of the antibody cocktail '
'administrated as nasal spray. The nasal spray is generally safe and well tolerated without '
'treatment related severe abnormal effects. The antibody cocktail nasal spray demonstrated '
'nasal concentrations higher than the IC<jats:sub>90</jats:sub>of neutralization activity '
'against Omicron BA.4/5 even at 24 hours post dosing. Furthermore, nasal samples from the '
'study subjects demonstrated potent neutralization activity against Omicron BA.4/5 in an ex '
'vivo pseudovirus neutralization assay. Together, we provide a novel approach for NAb '
'regimens, a potentially highly effective product with broad applicable perspective in '
'depressing the infection risk of new epidemic variant and ameliorating the heavy medical '
'burden of hospital.</jats:p><jats:sec><jats:title>One Sentence Summary</jats:title><jats:p>An '
'intranasal spray of two synergetic antibodies cocktail neutralizing Omicron BA.4/5 and an '
'initial clinical evaluation in healthy volunteers.</jats:p></jats:sec>',
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