Discussion
infection, death, –27·7, pain
VIRUS, ASYMPTOMATIC SARS-COV-2 INFECTION, DISEASE, INFECTION, DISEASES, INFLUENZA
To our knowledge, this study is the first report on the efficacy of a mucosal SARS-CoV-2 vaccine in a large-scale phase 3 trial. The favourable safety profile observed in early phase clinical trialsCompared with parenteral injection, intranasal vaccination offers the advantages of being needle-free and non-invasive, thereby eliminating the pain and fear commonly associated with administration. Moreover, our study has shown the safety of the dNS1-RBD intranasal spray vaccine, including in older people (aged ≥60 years), in individuals with underlying medical conditions, and in those with respiratory or nose-related diseases. The widespread acceptance and ease of administration of intranasal vaccination hold promise for diminishing vaccine hesitancy and extending immunisation coverage during viral outbreaks, thereby alleviating disease burden, especially among vulnerable populations.Although currently licensed SARS-CoV-2 vaccines might be effective against severe disease or death caused by some SARS-CoV-2 variants,To date, efficacy data from randomised controlled clinical trials conducted during the omicron-dominant phase have rarely been reported, and those available mostly assessed vaccine efficacy in SARS-CoV-2 naive children (without infection or vaccination history). In the observer-blinded, placebo-controlled trial of mRNA-1273 (elasomeran, Spikevax; Moderna Biotech, Cambridge, MA, USA) published in 2022, the vaccine efficacy at around 70 days after the second dose against symptomatic SARS-CoV-2 infection caused by omicron (B.1.1.529) was 46·4% (95% CI 19·8 to 63·8) in children aged 2–5 years and 31·5% (–27·7 to 62·0) in children aged 6–23 months, which are lower than that against previously circulating variants of concern.The most crucial challenge faced in the ongoing control of COVID-19 is the need for annual re-vaccination with updated formulations of the vaccines that often do not keep up with the rapid pace of viral variation.Nonetheless, the development of mucosal SARS-CoV-2 vaccines encounters challenges. First, the complexity of local mucosal immune responses poses a challenge in comprehending the mechanisms by which dNS1-RBD elicits broad protection. Second, the lack of validated sampling and detection methods for assessing cellular immunological markers in respiratory tracts has impeded the identification of immunological markers strongly associated with protection. In early human clinical trials,Evidence suggests that the first infection and replication of SARS-CoV-2 occurs in the nasal epithelium,This trial has several limitations. First, it was not powered to assess efficacy against severe disease due to the small number of participants with severe COVID-19. We did not anticipate that the omicron sublineages would have stronger transmissibility and immune escape ability, but substantially attenuated pathogenicity.In conclusion, although this clinical trial did not meet the predefined efficacy criteria for success, we have shown the potential of this intranasal spray influenza virus vector-based SARS-CoV-2 vaccine as a safe and broad-spectrum next-generation vaccine. In-depth studies, such as real-world studies and mechanistic research, are ongoing.