Background The monkeypox virus(MPXV)has raised global health concerns due to its widespread transmission.This study evaluated the MPXV immunogenic antigens and the impact of vaccinia virus(VACV)vaccination and MPXV in...Background The monkeypox virus(MPXV)has raised global health concerns due to its widespread transmission.This study evaluated the MPXV immunogenic antigens and the impact of vaccinia virus(VACV)vaccination and MPXV infection on cross-reactive antibody responses to conserved proteins from representative MPXV strains that reflected the evolutionary trajectory.Methods Phylogenetic analyses were first conducted to reveal the evolutionary trajectory of MPXV from 1970 to 2024.A total of 84 serum samples were collected:42 from VACV-vaccinated individuals,12 from MPXV-infected participants in the early stage,13 from the late stage,and 17 from naive individuals.Demographic data,MPXV and HIV status,as well as other clinical information were collected using standardized forms.Immunogenicity,cross-reactive antibody responses,and amino acid similarity to 15 MPXV surface proteins were assessed using enzyme-linked immunosorbent assays,VACV neutralization tests,and sequence alignment.Data analysis methods included analysis of variance,Mann-Whitney U test,binary logistic regression,Pearson correlation,and linear regression,with a significance threshold of P<0.05.Results The 186 complete genome sequences were classified into different clades and lineages,ranging from clade Ia to clade IIb C.1.1.Individuals infected with MPXV demonstrated strong antibody responses to antigens A35R,B6R,H3L,and E8L.VACV-vaccinated individuals exhibited broader cross-reactivity,particularly against A21L(P=0.0003),A28L(P=0.0028),A29L(P=0.0324),G2R(P=0.0003),and H2R(P=0.0008),compared to MPXV-infected individuals.Pearson correlation analysis revealed significant associations(P=0.0049)between antibody responses and the amino acid sequence similarity with other orthopoxviruses.Furthermore,MPXV-infected individuals exhibited greater neutralizing activity against VACV than those VACV-vaccinated individuals(P<0.0001),while the vaccinated group retained cross-protective immunity even decades post-vaccination.Conclusions A35R,B6R,H3L,and E8L are the main immunogenic antigens of MPXV.VACV-vaccination triggers a cross-reactive antibody response to MPXV surface proteins.Our findings suggest the need for targeted vaccines and antibody treatments for MPXV,as well as the reintroduction of smallpox vaccinations with booster doses for highrisk groups.展开更多
Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonst...Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.展开更多
基金funded by the Nanjing Research Center for Infectious Diseases of Integrated Traditional Chinese and Western Medicine(YBZX2022 to Y.Z.)NATCM’s Project of High-level Construction of Key TCM Disciplines(025062006002)+4 种基金supported by funding from the National Natural Science Foundation of China(32270142 to P.W.)Shanghai Rising-Star Program(22QA1408800 to P.W.)the Program of Science and Technology Cooperation with Hong Kong,Macao and Taiwan(23410760500 to P.W.)support from Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University(No.SKLGE-2304)Xiaomi Young Talents Program.This study was also supported by Fudan Zhangjiang Institute.
文摘Background The monkeypox virus(MPXV)has raised global health concerns due to its widespread transmission.This study evaluated the MPXV immunogenic antigens and the impact of vaccinia virus(VACV)vaccination and MPXV infection on cross-reactive antibody responses to conserved proteins from representative MPXV strains that reflected the evolutionary trajectory.Methods Phylogenetic analyses were first conducted to reveal the evolutionary trajectory of MPXV from 1970 to 2024.A total of 84 serum samples were collected:42 from VACV-vaccinated individuals,12 from MPXV-infected participants in the early stage,13 from the late stage,and 17 from naive individuals.Demographic data,MPXV and HIV status,as well as other clinical information were collected using standardized forms.Immunogenicity,cross-reactive antibody responses,and amino acid similarity to 15 MPXV surface proteins were assessed using enzyme-linked immunosorbent assays,VACV neutralization tests,and sequence alignment.Data analysis methods included analysis of variance,Mann-Whitney U test,binary logistic regression,Pearson correlation,and linear regression,with a significance threshold of P<0.05.Results The 186 complete genome sequences were classified into different clades and lineages,ranging from clade Ia to clade IIb C.1.1.Individuals infected with MPXV demonstrated strong antibody responses to antigens A35R,B6R,H3L,and E8L.VACV-vaccinated individuals exhibited broader cross-reactivity,particularly against A21L(P=0.0003),A28L(P=0.0028),A29L(P=0.0324),G2R(P=0.0003),and H2R(P=0.0008),compared to MPXV-infected individuals.Pearson correlation analysis revealed significant associations(P=0.0049)between antibody responses and the amino acid sequence similarity with other orthopoxviruses.Furthermore,MPXV-infected individuals exhibited greater neutralizing activity against VACV than those VACV-vaccinated individuals(P<0.0001),while the vaccinated group retained cross-protective immunity even decades post-vaccination.Conclusions A35R,B6R,H3L,and E8L are the main immunogenic antigens of MPXV.VACV-vaccination triggers a cross-reactive antibody response to MPXV surface proteins.Our findings suggest the need for targeted vaccines and antibody treatments for MPXV,as well as the reintroduction of smallpox vaccinations with booster doses for highrisk groups.
基金supported by the National Natural Science Foundation of China(No.82104353)China Postdoctoral Science Foundation funded project(No.2022M711680).
文摘Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.
