Mucosal COVID-19 vaccines in clinical development

Mucosal vaccines are designed to elicit both a strong systemic and mucosal immune response gaining importance as the next generation of vaccines to combat the respiratory coronavirus disease 2019 (COVID-19). The ability of these vaccines to induce mucosal immune responses in the upper respiratory tract may allow efficient prevention of infection and transmission, which could potentially reduce virus circulation in the population. In addition, they have the advantage that they can be administered by non-medical personnel and without needles. Several preclinical studies in small animal models and non-human primates, but also early phase clinical studies confirmed the capability of mucosal COVID-19 candidate vaccines to induce long-lasting immunity and to provide protection against an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to five vaccines which are already approved/licensed, at least 28 mucosal COVID-19 vaccines, based on different vaccine platforms, are currently being tested in clinical trials. However, clinical data for most of the conducted and completed clinical trials are not publicly available yet. In addition, several initiated trials have been terminated or were withdrawn. In this review, we aim to discuss the advantages and disadvantages of mucosal COVID-19 vaccines and to summarize the current status of mucosal COVID-19 vaccines in clinical development, with an emphasis on the most advanced candidates and the key findings observed in preclinical animal models and clinical studies.