Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron
Xinghai Zhang, … , Sandra Chiu, Ailong Huang
Xinghai Zhang, … , Sandra Chiu, Ailong Huang
Published April 8, 2024
Citation Information: JCI Insight. 2024;9(7):e171034. https://doi.org/10.1172/jci.insight.171034.
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Clinical Medicine COVID-19 Immunology

Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron

Abstract

BACKGROUND As Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection in the respiratory tract. Thus, elucidating the prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODS The applicable potential of a nasal spray cocktail containing 2 NAbs was characterized by testing its neutralizing potency, synergetic neutralizing mechanism, emergency protective and therapeutic efficacy in a hamster model, and pharmacokinetics/pharmacodynamic (PK/PD) in human nasal cavity.RESULTS The 2 NAbs displayed broad neutralizing efficacy against Omicron, and they could structurally compensate each other in blocking the Spike-ACE2 interaction. When administrated through the intranasal mucosal route, this cocktail demonstrated profound efficacy in the emergency prevention in hamsters challenged with authentic Omicron BA.1. The investigator-initiated trial in healthy volunteers confirmed the safety and the PK/PD of the NAb cocktail delivered via nasal spray. Nasal samples from the participants receiving 4 administrations over a course of 16 hours demonstrated potent neutralization against Omicron BA.5 in an ex vivo pseudovirus neutralization assay.CONCLUSION These results demonstrate that the NAb cocktail nasal spray provides a good basis for clinical prophylactic efficacy against Omicron infections.TRIAL REGISTRATION www.chictr.org.cn, ChiCTR2200066525.FUNDING The National Science and Technology Major Project (2017ZX10202203), the National Key Research and Development Program of China (2018YFA0507100), Guangzhou National Laboratory (SRPG22-015), Lingang Laboratory (LG202101-01-07), Science and Technology Commission of Shanghai Municipality (YDZX20213100001556), and the Emergency Project from the Science & Technology Commission of Chongqing (cstc2021jscx-fyzxX0001).

Authors

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

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Figure 6

Clinical study of A8G6 cocktail showed nasal NAbs concentration above the IC90 neutralization activity on pseudotyped Omicron BA.5 in cohorts 2–4.

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Clinical study of A8G6 cocktail showed nasal NAbs concentration above th...
Operational scheme was listed for cohort 2–4, showing intranasal administration (bold red arrow) of 4 doses of 0.7 mg A8G6 per day over 3 days (n = 12), 7 days (n = 12), and 14 days (n = 36), respectively. In Cohort 2 and Cohort 3, nasal samples were taken 0.5 hours before the second dose on Day 1 and before the last dose on the last day, with indicated side of the nostril (blue arrow). For the postadministration period, sampling was taken 12, 24, and 72 hours after the last dose with indicated side of the nostril. In Cohort 4, nasal samples were taken 0.5 hours before the second dose on Day 1 and Day 8, and 0.25 hours before the last dose. For the postadministration period, samples were taken 1, 4, 12, 48, 72, and 144 hours after the last dose. (A–C) ELISA of washed nasal samples to detect A8G6 nostril concentrations of cohorts 2–4. Baseline samples were taken 24 hours prior to the first dose. Data are presented in box-and-whiskers plots with maximal and minimal data points (whiskers) and medians (lines). Dashed lines indicate IC90 and IC99 established earlier from the pseudoviral neutralization assay of BA.5.