Research in context
respiratory infectious diseases
CORONAVIRUS, VIRUS, ADVERSE EVENT, INFLUENZA

We searched PubMed for clinical trials published from database inception to June 27, 2023, with the following terms: “(intranasal OR nasal OR mucosal OR aerosolized OR inhaled) AND (coronavirus OR COVID-19 OR SARS-CoV-2) AND (vaccine) AND (clinical trial)”. No language restrictions were applied. In addition to dNS1-RBD reported in this Article, the results associated with two other mucosal vaccines have been reported in peer-reviewed clinical trials, but without information on their efficacy. In an open-label phase 1 trial (
To our knowledge, this study is the first to report efficacy data for an intranasal SARS-CoV-2 vaccine. We evaluated the safety and efficacy of dNS1-RBD with a two-dose regimen in this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. The results indicated that dNS1-RBD was well tolerated, with no vaccine-related serious adverse event reported. This trial did not meet the predefined efficacy criteria for success, but based on efficacy data, it can be preliminarily inferred that dNS1-RBD provides sustained protection without a rapid decline (≥15 days with a median follow-up duration of 161 days).
There remains a need for clinical development of safe, broad-spectrum, and needle-free vaccines to protect against SARS-CoV-2 variants. As an intranasal SARS-CoV-2 vaccine developed using the ancestral SARS-CoV-2 strain, the available evidence suggests that the NS1-deleted and cold-adapted influenza virus vector-based SARS-CoV-2 vaccine is well tolerated and protects against COVID-19 caused by omicron variants. Our findings support the development of intranasal spray vaccines or other mucosal vaccines for respiratory infectious diseases and further investigation of the underlying protection mechanisms.