A review of currently licensed mucosal COVID-19 vaccines

The rapid development and deployment of injectable coronavirus disease 2019 (COVID-19) vaccines - in combination with non-pharmaceutical interventions and development of treatment options - significantly contributed to a decrease in both infection and mortality rates during the pandemic and saved millions of lives. However, injectable vaccines do not robustly and consistently induce a mucosal immune response, which is considered a key factor to prevent infection with and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, a tremendous effort is being made globally to develop next generation COVID-19 vaccines, which are capable of inducing a robust mucosal immune response in addition to a strong systemic cellular and humoral immune response. Mucosal COVID-19 vaccines have been evaluated successfully in preclinical and clinical trials, in which protection against SARS-CoV-2 infection has been demonstrated. This protective efficacy was associated with the upregulation of secretory IgA antibodies and the maturation of tissue-resident memory cells in the respiratory tract, which, together with an induced systemic immune response, significantly reduced viral replication and transmission in animal models. However, only five active mucosal vaccines (plus one 'passive' vaccine) have received approval for human use and robust data on their efficacy in inducing mucosal immune responses in humans and in blocking infection and transmission are missing. This highlights the importance of expanded research in this field. In this review, we aim to summarize what is known about these currently licensed vaccines, with an emphasis on the key findings obtained in both preclinical and clinical studies.