Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over othe...Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over other Omicron variants(Tamura et al.,2023).However,second-generation vaccines,including the BA.2 or BA.5 bivalent vaccine boosters,did not produce robust neutralization against the newly emerged XBB.1 or EG.5(Zou et al.,2023).Compared with variants BA.2 and BA.5,XBB.1 carries more mutations in the receptor binding domain(RBD)and exhibits significant immune evasion(Wang et al.,2023b).XBB.1 and its descendent lineages have rapidly become the dominant SARS-CoV-2 strain and are causing the next global wave of COVID-19.Therefore,it is essential to develop an updated vaccine against the newly emerged SARS-CoV-2 variants.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
Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurpris...Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurprisingly,these new subvariants are quickly gaining prevalence worldwide.In fact,some of them have outcompeted BA.5 in the USA according to CDC’s national genomic surveillance data in which,as of 6th February 2023,XBB.1.5,BQ.1.1,BQ.1,XBB and BF.7 have achieved a dominance of 66.4%,19.9%,7.3%,2.3%and 0.5%in the USA,as compared to 0.5%for BA.5.In this report,using plasma samples collected from individuals following different vaccination strategies and COVID-19 convalescent donors,we performed pseudoviral neutralization assays to confirm severe reductions in neutralization titers against BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5 in comparison to other Omicron sub-lineages.XBB and XBB.1.5 were shown to be remarkably resistant to plasma neutralization in all tested cohorts.By comparing the differential neutralization profiles,we found that a heterologous booster with an aerosolized vaccine following 2 doses of inactivated vaccine seemed to be superior to other vaccination strategies.展开更多
基金supported by a grant from the National Key R&D Program of China(2023YFC3041600 YW,the National Natural Science Foundation of China(82025001 JZ,92369113 YW,82172240 YW)Guangdong Basic and Applied Research Projects(2023B1515020040 YW,2021B1515130005 JZ,2021B1212030016 JD,2021A1111100009 JD)+7 种基金Science and Technology Planning Project of Guangzhou City(2023A04J1279 LZ)ZhongNanShan Medical Foundation of Guangdong Province(ZNSA-2020013 JZ)the Science and Technology Project of General Administration of Customs,P.R.China(2023HK065 LZ)State Key Laboratory of Respiratory Disease(SKLRD-Z-202214,SKLRD-OP-202309 YW,SKLRD-Z-202411 LZ)the Self-supporting Program of Guangzhou Laboratory(GZNL2023A01006,SRPG22-001)Guangzhou Medical University(YP2022005 YW)Korea Institute of Planning and Evaluation for Technology in Food,Agriculture and Forestry(IPET)through Animal Disease Management Technology Advancement Support Program,funded by the Ministry of Agriculture,Food and Rural Affairs(MAFRA)(122012-2,122060-2 JZ)the National Clinical Research Center for Respiratory Disease(BRD-NCRCRD,Guangzhou,Southern China).Patronus Biotech is a company researching virus-like particle display technology and vaccines.Yu Zhou and Jing Jin are named inventors on a patent invention relating to the described novel SARS-CoV-2 virus-like particle vaccine.All BALB/c mouse experiments complied with relevant ethical regulations for animal research and were approved by the LUYE PHARMA Animal Experimentation Ethics Committee.The K18-hACE2 mouse experiment was reviewed and approved by the Institutional Animal Care and Use Committees of Guangzhou Medical University(2023-0451).All authors declare that they have no conflict of interests.
文摘Dear Editor,The newly emerged severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron subvariants(XBB.1,EG.5 and JN.1)and sublineages have been circulating globally with superior growth advantages over other Omicron variants(Tamura et al.,2023).However,second-generation vaccines,including the BA.2 or BA.5 bivalent vaccine boosters,did not produce robust neutralization against the newly emerged XBB.1 or EG.5(Zou et al.,2023).Compared with variants BA.2 and BA.5,XBB.1 carries more mutations in the receptor binding domain(RBD)and exhibits significant immune evasion(Wang et al.,2023b).XBB.1 and its descendent lineages have rapidly become the dominant SARS-CoV-2 strain and are causing the next global wave of COVID-19.Therefore,it is essential to develop an updated vaccine against the newly emerged SARS-CoV-2 variants.
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.
基金Key R&D Program of China(2021YFC2300101 YW)the National Natural Science Foundation of China(82172240 YW,82025001 JZ)+4 种基金Self-supporting Program of Guangzhou Laboratory(SRPG22-001,SRPG22-006)Guangdong Basic and Applied Research Projects(2023B1515020040 YW,2020A0505100063 JZ,2019B1515120068 JZ)ZhongNanShan Medical Foundation of Guangdong Province(ZNSA-2020001,ZNSA-2020013)State Key Laboratory of Respiratory Disease(SKLRD-Z-202214 YW,SKLRD-OP-202309 YW)Guangzhou Medical University(YP2022005 YW).
文摘Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurprisingly,these new subvariants are quickly gaining prevalence worldwide.In fact,some of them have outcompeted BA.5 in the USA according to CDC’s national genomic surveillance data in which,as of 6th February 2023,XBB.1.5,BQ.1.1,BQ.1,XBB and BF.7 have achieved a dominance of 66.4%,19.9%,7.3%,2.3%and 0.5%in the USA,as compared to 0.5%for BA.5.In this report,using plasma samples collected from individuals following different vaccination strategies and COVID-19 convalescent donors,we performed pseudoviral neutralization assays to confirm severe reductions in neutralization titers against BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5 in comparison to other Omicron sub-lineages.XBB and XBB.1.5 were shown to be remarkably resistant to plasma neutralization in all tested cohorts.By comparing the differential neutralization profiles,we found that a heterologous booster with an aerosolized vaccine following 2 doses of inactivated vaccine seemed to be superior to other vaccination strategies.
