The role of cross-reactive immunity to emerging coronaviruses: Implications for novel universal mucosal vaccine design

Host immune response to coronaviruses and the role of cross-reactivity immunity among different coronaviruses are crucial for understanding and combating the continuing COVID-19 outbreak and potential subsequent pandemics. This review paper explores how previous exposure to common cold coronaviruses and more pathogenic coronaviruses may elicit a protective immune response against SARS-CoV-2 infection, and discusses the challenges posed by some variants of concern that may escape current vaccines. It also highlights the need for a mucosal universal vaccine that can induce long-term protection against current and emerging coronaviruses by leveraging cross-reactive immunity. We propose a novel mucosal universal vaccine that consists of crossreactive antigenic peptides with highly conserved epitopes among coronaviruses, conjugated with an immunostimulant adjuvant cytokine, including B-cell activating factor (BAFF). This vaccine may enhance the local mucosal adaptive response, induce tissue-resident memory cells, and inhibit viral replication and clearance. However, further research is required to evaluate its safety and efficacy. Keywords: cross-reactivity, mucosal vaccine, BAFF, B-cell, SARS-COV-2, COVID-19 [phrase omitted]