Why Should Vaccines against Respiratory Diseases Go Mucosal? B Cell Epitope-Based Vaccines against SARS-CoV-2

Immunity against respiratory pathogens is often short-term, and consequently there is an unmet need for effective prevention of such infections. One such infectious disease is 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 March 11, 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, con-tained 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 warrant-ed. In this review, we present the status of the systemic vaccines, of the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell pep-tide-based vaccination applied by prime-boost schedule for eliciting both systemic and mucosal immunity.