Mucosal antibodies are critical for protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection by limiting viral replication and transmission.While systemic immunity to SARS-CoV-2 is well-...Mucosal antibodies are critical for protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection by limiting viral replication and transmission.While systemic immunity to SARS-CoV-2 is well-characterized,the durability and protective efficacy of mucosal vaccines,especially during the recent JN.1 wave,are less understood.In this study,we conducted a longitudinal assessment of systemic and nasal immune responses in 34 individuals who had received the inhaled Ad5-XBB.1.5 vaccination at days 0,7,14,28,90,and 180 post-vaccination,using neutralization assays,immunoglobulin A/G(IgA/IgG)enzyme-linked immunosorbent assay(ELISA),T-cell staining,and Fc-effector function assays.Our results showed that mucosal vaccination preferentially induces IgA responses in both nasal mucosa and systemic circulation,with nasal IgA showing stronger correlation with neutralizing titers than IgG.However,nasal antibody responses declined significantly by 6 months post-vaccination,with most participants experiencing breakthrough infections during the JN.1 wave.Individuals with high pre-existing anti-Ad5 antibodies exhibited reduced vaccine-induced neutralizing responses.The Ad5-XBB.1.5 mucosal vaccine enhanced antigen-specific CD8^(+)T cell responses with a slight increase in Fc-mediated antibody-dependent cellular phagocytosis(ADCP),but failed to induce detectable CD4^(+)T cell responses.Collectively,our findings elucidate the limited durability of mucosal immunity post-vaccination and highlight the need for improved mucosal vaccine strategies that sustain and optimize nasal IgA responses.展开更多
基金supported by grants from the National Key Research and Development Program of China(grant number 2024YFA0920001 to Y.W.)the National Natural Science Foundation of China(grant numbers 82025001,82495200,and 82495203 to J.Z.,92369113 and 82172240 to Y.W.)+5 种基金Guangzhou National Laboratory and State Key Laboratory of Respiratory Disease(grant number GZNL2024B01001 to Y.W.)Selfsupporting Program of Guangzhou National Laboratory(grant number SRPG22-001 to Y.W.)Guangdong Basic and Applied Research Projects(grant number 2023B1515020040 to Y.W.)State Key Laboratory of Respiratory Disease(grant number SKLRD-Z-202411 to L.Z.)Science and Technology Planning Project of Guangzhou City(grant numbers 2023A04J1279 to L.Z.and 2024A03J1230 to J.Z.)the Science and Technology Project of General Administration of Customs,P.R.China(grant number 2023HK065 to L.Z.).
文摘Mucosal antibodies are critical for protection against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection by limiting viral replication and transmission.While systemic immunity to SARS-CoV-2 is well-characterized,the durability and protective efficacy of mucosal vaccines,especially during the recent JN.1 wave,are less understood.In this study,we conducted a longitudinal assessment of systemic and nasal immune responses in 34 individuals who had received the inhaled Ad5-XBB.1.5 vaccination at days 0,7,14,28,90,and 180 post-vaccination,using neutralization assays,immunoglobulin A/G(IgA/IgG)enzyme-linked immunosorbent assay(ELISA),T-cell staining,and Fc-effector function assays.Our results showed that mucosal vaccination preferentially induces IgA responses in both nasal mucosa and systemic circulation,with nasal IgA showing stronger correlation with neutralizing titers than IgG.However,nasal antibody responses declined significantly by 6 months post-vaccination,with most participants experiencing breakthrough infections during the JN.1 wave.Individuals with high pre-existing anti-Ad5 antibodies exhibited reduced vaccine-induced neutralizing responses.The Ad5-XBB.1.5 mucosal vaccine enhanced antigen-specific CD8^(+)T cell responses with a slight increase in Fc-mediated antibody-dependent cellular phagocytosis(ADCP),but failed to induce detectable CD4^(+)T cell responses.Collectively,our findings elucidate the limited durability of mucosal immunity post-vaccination and highlight the need for improved mucosal vaccine strategies that sustain and optimize nasal IgA responses.
