{Reference Type}: Journal Article {Title}: Independent Protection and Influence of the Spike-Specific Antibody Response of SARS-CoV-2 Nucleocapsid Protein (N) in Whole-Virion Vaccines. {Author}: Yang H;Xie Y;Lu S;Sun Y;Wang K;Li S;Wang J;Liao G;Li C; {Journal}: Vaccines (Basel) {Volume}: 11 {Issue}: 11 {Year}: 2023 Nov 2 {Factor}: 4.961 {DOI}: 10.3390/vaccines11111681 {Abstract}: Of all of the components in SARS-CoV-2 inactivated vaccines, nucleocapsid protein (N) is the most abundant and highly conserved protein. However, the function of N in these vaccines, especially its influence on the targeted spike protein's response, remains unknown. In this study, the immunization of mice with the N protein alone was shown to reduce the viral load, alleviating pulmonary pathological lesions after challenge with the SARS-CoV-2 virus. In addition, co-immunization and pre-immunization with N were found to induce higher S-specific antibody titers rather than compromise them. Remarkably, the same trend was also observed when N was administered as the booster dose after whole inactivated virus vaccination. N-specific IFN-γ-secreting T cell response was detected in all groups and exhibited a certain relationship with S-specific IgG antibody improvements. Together, these data indicate that N has an independent role in vaccine-induced protection and improves the S-specific antibody response to inactivated vaccines, revealing that an interplay mechanism may exist in the immune responses to complex virus components.