The ongoing COVID-19 pandemic has underscored the importance of strong immune defenses against emerging SARS-CoV-2 variants.While COVID-19 vaccines containing XBB subvariants have proven effective in neutralizing new ...The ongoing COVID-19 pandemic has underscored the importance of strong immune defenses against emerging SARS-CoV-2 variants.While COVID-19 vaccines containing XBB subvariants have proven effective in neutralizing new SARS-CoV-2 variants,a gap remains in knowledge regarding neutralizing antibody responses in older adults aged>65 years against these newly emerged variants.This study was therefore undertaken to investigate and compare neutralizing antibody responses to three XBB-containing protein-based vaccines(trivalent XBB.1.5 vaccine,bivalent Omicron XBB vaccine,and tetravalent XBB.1 vaccine)head-to-head in 90 individuals aged>65 years.The results showed that all three XBB-containing vaccines substantially enhanced the neutralizing antibody response,with 100%of vaccinees having detectable antibody titers against ancestral D614G and variants BA.5,XBB.1.5,JN.1,KP.2,and KP.3 after booster immunization.Subsequent analysis indicated that the trivalent XBB.1.5 and tetravalent XBB.1 vaccines elicited higher levels of neutralizing antibodies compared to the bivalent Omicron XBB vaccine.The KP.2 and KP.3 variants displayed antibody resistance comparable to the JN.1 variant.Older adults produce similar neutralizing antibody responses to the vaccines regardless of their underlying medical conditions.These findings indicate that booster vaccination with XBB-containing vaccines can effectively elicit strong neutralizing responses against a number of SARS-CoV-2 variants in older adults over 65 years,which will help guide vaccine strategies in this elderly population.展开更多
The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to presenttherapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN...The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to presenttherapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated as oneof the most immune-evasive variants, showing higher neutralization resistance compared to XBB.1.5. In this study, serum sampleswere collected from adult participants including those who had gone through the BA.5/BF.7, EG.5/HK.3 and XBB/JN.1 infectionwaves, characterized by different infection and vaccination histories. We evaluated the neutralization in these serum samples againstpseudoviruses of Omicron lineages. We further investigated humoral immune response of recombinant XBB vaccines againstOmicron variants and estimated the neutralization resistance of JN.1 sublineages, including KP.2 and KP.3. Our results showed thatsera from previous circulating Omicron subvariant breakthrough infections exhibited low neutralization against pseudoviruses ofOmicron lineages. The GMTs of 50% neutralization against all tested pseudoviruses were significantly elevated in sera fromindividuals who received WSK-V102C or WSK-V102D boosters. Importantly, the GMTs of 50% neutralization in serum samples fromindividuals 4 months after a WSK-V102D booster against XBB.1.5, JN.1, JN.1.13, KP.2 and KP.3 pseudoviruses were 3479, 1684, 1397,1247 and 1298, with 9.86-, 9.79-, 8.73-, 8.66- and 8.16-fold increase compared to those without booster, respectively, indicating thatboosting with XBB.1.5 subunit vaccines still induced strong antibody responses against JN.1 sublineages. However, JN.1 sublineages,including KP.2 and KP.3, revealed more than 2-fold decreases in neutralizing antibody titers compared to XBB.1.5, suggestingsignificantly enhanced neutralization evasion and the necessity of boosters based on JN.1, KP.2 or KP.3.展开更多
The emergence of XBB-and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations.In addition,the unfavorable impacts of immune imprinting,stemming f...The emergence of XBB-and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations.In addition,the unfavorable impacts of immune imprinting,stemming from continuous exposure to antigens from circulated viruses,have been observed to incline immune response against earlier lineages,thereby declining the neutralization to newly emerged Omicron subvariants.In response to this,the advancement of next-generation vaccines against COVID-19 targeting components from new subvariants such as XBB-lineage is imperative.In the current study,a self-assembled trimeric recombinant protein(RBDXBB.1.5-HR)was generated by concatenating the sequences of the receptor binding domain(RBD)derived from XBB.1.5 with heptad-repeat 1(HR1)and HR2 sequences from the spike S2 subunit.Adjuvanted-RBDXBB.1.5-HR induced robust humoral and cellular immune responses,characterized by elevated neutralization against JN.1-inculuded subvariants and a substantial population of antigen-specific T memory cells.Protective immunity conferred by RBDXBB.1.5-HR vaccine was preserved post-immunization,as evidenced by germinal center B(GC B)and T follicular helper(Tfh)responses,sustained neutralization potency,and an increase in memory B cells(MBCs)and long-lived plasma cells(LLPCs).The RBDXBB.1.5-HR vaccine showed a favorable boosting effect when administered heterologously after three doses of inactivated virus(IV)and mRNA vaccines.Significantly,it provided protection against live Omicron EG.5.1 viruses in vivo.The monovalent RBDXBB.1.5-HR vaccine showed favorable safety and immunogenicity,boosting neutralizing antibodies against JN.1-and XBB-lineage subvariants in individuals with prior COVID-19 vaccinations.These findings highlight its clinical potential in safeguarding against circulating Omicron subvariants.展开更多
Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA...Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.展开更多
基金supported by grants from the National Natural Science Foundation of China(82273692 and 92169207).
文摘The ongoing COVID-19 pandemic has underscored the importance of strong immune defenses against emerging SARS-CoV-2 variants.While COVID-19 vaccines containing XBB subvariants have proven effective in neutralizing new SARS-CoV-2 variants,a gap remains in knowledge regarding neutralizing antibody responses in older adults aged>65 years against these newly emerged variants.This study was therefore undertaken to investigate and compare neutralizing antibody responses to three XBB-containing protein-based vaccines(trivalent XBB.1.5 vaccine,bivalent Omicron XBB vaccine,and tetravalent XBB.1 vaccine)head-to-head in 90 individuals aged>65 years.The results showed that all three XBB-containing vaccines substantially enhanced the neutralizing antibody response,with 100%of vaccinees having detectable antibody titers against ancestral D614G and variants BA.5,XBB.1.5,JN.1,KP.2,and KP.3 after booster immunization.Subsequent analysis indicated that the trivalent XBB.1.5 and tetravalent XBB.1 vaccines elicited higher levels of neutralizing antibodies compared to the bivalent Omicron XBB vaccine.The KP.2 and KP.3 variants displayed antibody resistance comparable to the JN.1 variant.Older adults produce similar neutralizing antibody responses to the vaccines regardless of their underlying medical conditions.These findings indicate that booster vaccination with XBB-containing vaccines can effectively elicit strong neutralizing responses against a number of SARS-CoV-2 variants in older adults over 65 years,which will help guide vaccine strategies in this elderly population.
基金supported by the Young Scientists Fund of National Natural Science Foundation of China(No.82200018)National Natural Science Foundation of China(No.32400776)+1 种基金China Postdoctoral Science Foundation(No.2023T160458)the Project of the Science and Technology Department of Sichuan Province(No.2023NSFSC1655).
文摘The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to presenttherapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated as oneof the most immune-evasive variants, showing higher neutralization resistance compared to XBB.1.5. In this study, serum sampleswere collected from adult participants including those who had gone through the BA.5/BF.7, EG.5/HK.3 and XBB/JN.1 infectionwaves, characterized by different infection and vaccination histories. We evaluated the neutralization in these serum samples againstpseudoviruses of Omicron lineages. We further investigated humoral immune response of recombinant XBB vaccines againstOmicron variants and estimated the neutralization resistance of JN.1 sublineages, including KP.2 and KP.3. Our results showed thatsera from previous circulating Omicron subvariant breakthrough infections exhibited low neutralization against pseudoviruses ofOmicron lineages. The GMTs of 50% neutralization against all tested pseudoviruses were significantly elevated in sera fromindividuals who received WSK-V102C or WSK-V102D boosters. Importantly, the GMTs of 50% neutralization in serum samples fromindividuals 4 months after a WSK-V102D booster against XBB.1.5, JN.1, JN.1.13, KP.2 and KP.3 pseudoviruses were 3479, 1684, 1397,1247 and 1298, with 9.86-, 9.79-, 8.73-, 8.66- and 8.16-fold increase compared to those without booster, respectively, indicating thatboosting with XBB.1.5 subunit vaccines still induced strong antibody responses against JN.1 sublineages. However, JN.1 sublineages,including KP.2 and KP.3, revealed more than 2-fold decreases in neutralizing antibody titers compared to XBB.1.5, suggestingsignificantly enhanced neutralization evasion and the necessity of boosters based on JN.1, KP.2 or KP.3.
基金supported by the National Key Research and Development Program of China(2024YFC2310700,X.W.)1.3.5 project for disciplines of excellence from West China Hospital of Sichuan University(ZYGD23038,X.W)+3 种基金National Natural Science Foundation Regional Innovation and Development(No.U19A2003)National Natural Science Foundation of China(82200018,Jingyun Yang)China Postdoctoral Science Foundation(No.2023T160458,Jingyun Yang)National Natural Science Foundation of China Young Student Basic Research Program(323B2050,W.H).
文摘The emergence of XBB-and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations.In addition,the unfavorable impacts of immune imprinting,stemming from continuous exposure to antigens from circulated viruses,have been observed to incline immune response against earlier lineages,thereby declining the neutralization to newly emerged Omicron subvariants.In response to this,the advancement of next-generation vaccines against COVID-19 targeting components from new subvariants such as XBB-lineage is imperative.In the current study,a self-assembled trimeric recombinant protein(RBDXBB.1.5-HR)was generated by concatenating the sequences of the receptor binding domain(RBD)derived from XBB.1.5 with heptad-repeat 1(HR1)and HR2 sequences from the spike S2 subunit.Adjuvanted-RBDXBB.1.5-HR induced robust humoral and cellular immune responses,characterized by elevated neutralization against JN.1-inculuded subvariants and a substantial population of antigen-specific T memory cells.Protective immunity conferred by RBDXBB.1.5-HR vaccine was preserved post-immunization,as evidenced by germinal center B(GC B)and T follicular helper(Tfh)responses,sustained neutralization potency,and an increase in memory B cells(MBCs)and long-lived plasma cells(LLPCs).The RBDXBB.1.5-HR vaccine showed a favorable boosting effect when administered heterologously after three doses of inactivated virus(IV)and mRNA vaccines.Significantly,it provided protection against live Omicron EG.5.1 viruses in vivo.The monovalent RBDXBB.1.5-HR vaccine showed favorable safety and immunogenicity,boosting neutralizing antibodies against JN.1-and XBB-lineage subvariants in individuals with prior COVID-19 vaccinations.These findings highlight its clinical potential in safeguarding against circulating Omicron subvariants.
基金supported by a grant(2023YFC2307600,to Z.J.Z.)from the Na-tional Key Research and Development Program of Chinaa grant(202102AA100051,to Z.J.Z.)from the Yunnan Provincial Sci-ence and Technology Department,China+2 种基金a grant(H-2018102,to J.W.)from the High-level Health Technical Personnel Project of Yunnan Province,Chinaa grant(2022SCP001,to Z.J.Z.)from the Spring City Plan:The High-level Talent Promotion and Training Project of Kunmingand a grant(32371000,to C.M.L.)from the National Natural Science Foundation of China.
文摘Periodically updating coronavirus disease 19(COVID-19)vaccines that offer broad-spectrum protection is needed giventhe strong immune evasion by the circulating omicron sublineages.The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate.We initiated an observer-blinded,threearms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three dosesCOVID-19 vaccine.Immunogenicity in terms of neutralizing antibodies elicited by a 30-mg dose of XBB.1.5-containingbivalent vaccine(RQ3027),a 30-mg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine(RQ3025)and their precedent 30-mg Alpha/Beta(combined mutations)monovalent mRNA vaccine(RQ3013)and safety are primary and secondary endpoints,respectively.We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines.RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies(NAbs)against XBB.1.5,XBB.1.16,XBB.1.9.1,and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection.All study vaccines were welltolerated without serious adverse reactions identified.The incidence rates per 1000 person-years of COVID-19 casesduring the 2nd-19th week after randomization were lowest in RQ3027.Overall,our data show that XBB.1.5-containingbivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalentwith no new safety concerns.
