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Considering the ongoing need for new COVID\u201019 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS\u2010CoV\u20102 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T\u2010cell epitopes critical for SARS\u2010CoV\u20102 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID\u201019 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long\u2010lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long\u2010lasting, and it can persist up to 11 years post\u2010infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID\u201019 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. 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