Nasal spray of an IgM‐like ACE2 fusion protein HH‐120 prevents SARS‐CoV‐2 infection: Two investigator‐initiated postexposure prophylaxis trials
Rui Song, Xiaoyou Chen, Baoliang Li, Jun Ni, Yunao Zhou, Hongbin Zhang, Xiao Liang, Liangfeng Zou, Juan Liu, Fang Yang, Guangyu Li, Xiaodi Guo, Zhe Liu, Fengfeng Mao, Cong Lei, Jianhua Sui, Wenhui Li, Ronghua Jin
Journal of Medical Virology, doi:10.1002/jmv.29275
HH-120, an IgM-like angiotensin converting enzyme 2 (ACE2) fusion protein, has been developed as a nasal spray against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently undergoing human trials. HH-120 nasal spray was assessed for postexposure prophylaxis (PEP) in two investigatorinitiated (NS01 and NS02) trials with different risk levels of SARS-CoV-2 exposure. NS01 enrolled family caregiver participants who had continuous contacts with laboratory-confirmed index cases; NS02 enrolled participants who had general contacts (Part 1) or close contacts (Part 2) with index cases. The primary endpoints were safety and laboratory-confirmed and/or symptomatic SARS-CoV-2 infection. In NS01 trial (14 participants), the SARS-CoV-2 infection rates were 25% in the HH-120 group and 83.3% in the external control group (relative risk reduction [RRR]: 70.0%). In NS02-Part 1 (193 participants), the infection rates were 4% (HH-120) versus 11.3% (placebo), symptomatic infection rates were 0.8% versus 3.5%, hence with a RRR of 64.6% and 77.1%, respectively. In Part 2 (76 participants), the infection rates were 17.1% (HH-120) versus 30.4% (placebo), symptomatic infection rates were 7.5% versus 27.3%, with a RRR of 43.8% and 72.5%, respectively. No HH-120-related serious adverse effects were observed. The HH-120 nasal spray used as PEP was safe and effective in preventing laboratory-confirmed and symptomatic SARS-CoV-2 infection.
While this study provides valuable insights into the potential benefits of the HH-120 nasal spray in preventing SARS-CoV-2 infection, there are several limitations that should be taken into consideration. First, the sample sizes were relatively small, and the number of events were relatively low, despite all participants received consecutive NAAT for SARS-CoV-2 to capture every event after enrollment. Second, these trials were conducted during a period when there were strict policies of intensive contact tracing and quarantine, and in closed settings in China. Therefore, the realworld efficacy of the HH-120 nasal spray in post-pandemic with no strict surveillance remains to be assessed. Third, in the NS02 trial, the exact durations of participants' exposure to the index cases before enrollment could not be accurately measured, which could potentially introduce bias into the study. Variations in participants' exposure durations arise from the nature of this type of study, which involves retrospective data collection or relies on participants' self-reporting. Finally, all the participants were in a quarantine status, which prevented us from assessing the ability of the HH-120 nasal spray to produce a beneficial effect in reducing the transmission of SARS-CoV-2. In summary, our study provides compelling preliminary evidence that the HH-120 nasal spray is highly effective in protecting individuals who had been exposed to SARS-CoV-2 from the laboratory-confirmed and symptomatic..
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