Publication date: Jul 18, 2024
Immunity against respiratory pathogens is often short-term, and, consequently, there is an unmet need for the effective prevention of such infections. One such infectious disease is coronavirus disease 19 (COVID-19), which is caused by the novel Beta coronavirus SARS-CoV-2 that emerged around the end of 2019. The World Health Organization declared the illness a pandemic on 11 March 2020, and since then it has killed or sickened millions of people globally. The development of COVID-19 systemic vaccines, which impressively led to a significant reduction in disease severity, hospitalization, and mortality, contained the pandemic’s expansion. However, these vaccines have not been able to stop the virus from spreading because of the restricted development of mucosal immunity. As a result, breakthrough infections have frequently occurred, and new strains of the virus have been emerging. Furthermore, SARS-CoV-2 will likely continue to circulate and, like the influenza virus, co-exist with humans. The upper respiratory tract and nasal cavity are the primary sites of SARS-CoV-2 infection and, thus, a mucosal/nasal vaccination to induce a mucosal response and stop the virus’ transmission is warranted. In this review, we present the status of the systemic vaccines, both the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell peptide-based vaccination applied by a prime-boost schedule to elicit both systemic and mucosal immunity.