Human adenoviruses(HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3,-7,-4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respi...Human adenoviruses(HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3,-7,-4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population.Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies(NAb) against HAdV-3,-4,-7,-14,-55,and-11 in total 278 healthy populations between 0 months and 49 years of age(228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1–2, 3–5, and 6–17 years,respectively. The seroprevalence was very low(0% - 8.1%) for all other four types. In adults aged between 18 and49 years, HAdV-3,-4, and-7(> 50.00%) were the most common types, followed by HAdV-14(38.00%),-55(34.00%),and-11(24.00%). Adults tended to have high NAb titers against HAdV-4 and-55. HAdV-55-seropositive donors tended to be HAdV-11-and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14,-55,-11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.展开更多
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 the National Key Research and Development Program of China (2018YFC1200100)the Guangzhou Science and Technology Program Key Project, China (201803040004)+2 种基金the National Science and Technology Major Project of China (2017ZX10103011003, 2018ZX10102001)the National Natural Science Foundation of China, China (31570163)the Youth Project of State Key Laboratory of Respiratory Disease, China (SKLRD-QN-201713)。
文摘Human adenoviruses(HAdVs) commonly cause many diseases such as respiratory diseases, gastroenteritis, cystitis worldwide. HAdV-3,-7,-4 and emergent HAdV-55 and HAdV-14 are the most important types causing severe respiratory diseases. There is no effective drug available for clinical treatment, and no vaccine available for the general population.Therefore, it is important to investigate the seroprevalence against HAdV for developing novel vaccines and vectors. In this study, we investigated the seroprevalence and titer levels of neutralizing antibodies(NAb) against HAdV-3,-4,-7,-14,-55,and-11 in total 278 healthy populations between 0 months and 49 years of age(228 children and 50 adults) from Guangzhou. In children under the age of 18 years, the seropositive rates were significantly increased against HAdV-3 at12.07%, 33.96%, and 64.29% and against HAdV-7 at 0%, 18.87%, and 19.05% in age groups of 1–2, 3–5, and 6–17 years,respectively. The seroprevalence was very low(0% - 8.1%) for all other four types. In adults aged between 18 and49 years, HAdV-3,-4, and-7(> 50.00%) were the most common types, followed by HAdV-14(38.00%),-55(34.00%),and-11(24.00%). Adults tended to have high NAb titers against HAdV-4 and-55. HAdV-55-seropositive donors tended to be HAdV-11-and HAdV-14-seropositive. These results indicated the low level of herd immunity against all six HAdV types in young children, and HAdV-14,-55,-11 in adults from Guangzhou City. Our findings demonstrate the importance of monitoring HAdV types and developing vaccines against HAdV for children and adults.
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.
