Background The longitudinal antigen-specific immunity in COVID-19 convalescents is crucial for long-term protection upon individual re-exposure to SARS-CoV-2, and even more pivotal for ultimately achieving population-level immunity. To better understand the features of immune memory in individuals with different disease severities at one year post-disease onset we conducted this cohort study. Methods We conducted a systematic antigen-specific immune evaluation in 101 COVID-19 convalescents, who had asymptomatic, mild, moderate, or severe disease, through two visits at months 6 and 12 post-disease onset. The SARS-CoV-2-specific antibodies, comprising NAb, IgG, and IgM, were assessed by mutually corroborated assays, i.e. neutralization, enzyme-linked immunosorbent assay (ELISA), and microparticle chemiluminescence immunoassay (MCLIA). Meanwhile, the T-cell memory against SARS-CoV-2 spike, membrane and nucleocapsid proteins was tested through enzyme-linked immunospot assay (ELISpot), intracellular cytokine staining (ICS), and tetramer staining-based flow cytometry, respectively. Results SARS-CoV-2-specific IgG antibodies, and also NAb can persist among over 95% COVID-19 convalescents from 6 months to 12 months after disease onset. At least 19/71 (26%) of COVID-19 convalescents (double positive in ELISA and MCLIA) had detectable circulating IgM antibody against SARS-CoV-2 at 12m post-disease onset. Notably, the percentages of convalescents with positive SARS-CoV-2-specific T-cell responses (at least one of the SARS-CoV-2 antigen S1, S2, M and N protein) were 71/76 (93%) and 67/73 (92%) at 6m and 12m, respectively. Furthermore, both antibody and T-cell memory levels of the convalescents were positively associated with their disease severity. Conclusions SARS-CoV-2-specific cellular and humoral immunities are durable at least until one year after disease onset.
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Emerging in December 2019, coronavirus disease 2019 (COVID-19) eventually became a pandemic and has posed a tremendous threat to global public health. However, the origins of SARS-CoV-2, the causative agent of COVID-19, remain to be determined. It has reported that a certain number of the early case clusters had a contact history with Huanan Seafood Market. Therefore, surveillance of SARS-CoV-2 within the market is of vital importance. Herein, we presented the SARS-CoV-2 detection results of 1380 samples collected from the environment and the animals within the market in early 2020. By SARS-CoV-2-specific RT-qPCR, 73 environmental samples tested positive for SARS-CoV-2 and three live viruses were successfully isolated. The viruses from the market shared nucleotide identity of 99.980% to 99.993% with the human isolate HCoV/Wuhan/IVDC-HB-01. In contrast, no virus was detected in the animal swabs covering 18 species of animals in the market. The SARS-COV-2 nucleic acids in the positive environmental samples showed significant correlation of abundance of Homo sapiens with SARS-CoV-2. In summary, this study provided convincing evidence of the prevalence of SARS-CoV-2 in the Huanan Seafood Market during the early stage of COVID-19 outbreak.
Human leukocyte antigen (HLA) alleles have a high degree of polymorphism, which determines their peptide-binding motifs and subsequent T-cell receptor recognition. The simplest way to understand the cross-presentation of peptides by different alleles is to classify these alleles into supertypes. A1 and A3 HLA supertypes are widely distributed in humans. However, direct structural and functional evidence for peptide presentation features of key alleles (e.g., HLA-A * 30:01 and -A * 30:03) are lacking. Herein, the molecular basis of peptide presentation of HLA-A * 30:01 and -A * 30:03 was demonstrated by crystal structure determination and thermostability measurements of complexes with T-cell epitopes from influenza virus (NP44), human immunodeficiency virus (RT313), and Mycobacterium tuberculosis (MTB). When binding to the HIV peptide, RT313, the PΩ-Lys anchoring modes of HLA-A * 30:01, and -A * 30:03 were similar to those of HLA-A * 11:01 in the A3 supertype. However, HLA-A * 30:03, but not -A * 30:01, also showed binding with the HLA * 01:01-favored peptide, NP44, but with a specific structural conformation. Thus, different from our previous understanding, HLA-A * 30:01 and -A * 30:03 have specific peptide-binding characteristics that may lead to their distinct supertype-featured binding peptide motifs. Moreover, we also found that residue 77 in the F pocket was one of the key residues for the divergent peptide presentation characteristics of HLA-A * 30:01 and -A * 30:03. Interchanging residue 77 between HLA-A * 30:01 and HLA-A * 30:03 switched their presented peptide profiles. Our results provide important recommendations for screening virus and tumor-specific peptides among the population with prevalent HLA supertypes for vaccine development and immune interventions.
Influenza A viruses (IAVs) and influenza B viruses (IBVs) cause annual epidemics in human populations with seasonal circulation spikes. Peptide AM58–66GL9 located at residues 58–66 of M1 protein of IAVs has been recognized as an immunodominant T cell epitope with HLA-A*0201 restriction and broadly used as a positive reference in influenza immunity. This peptide also almost completely overlaps with a nuclear export signal (NES) 59–68 in IAV M1, which explains the limited escape mutations under the T cell immune pressure in this region. In this study, we investigated the potential immunogenicity and NES in the corresponding region of IBV. The long peptide covering this region can be recognized by specific T cells and induce robust expression of IFN-γ among HLA-B*1501 donors in vivo, but not in HLA-A*0201 donors. Among a series of truncated peptides derived from this region, we identified an immunodominant HLA-B*1501–restricted T cell epitope BM58–66AF9 (ALIGASICF) in the M1 protein of IBV. Furthermore, the structure of the HLA-B*1501/BM58–66AF9 complex shows that BM58–66AF9 performs a flat and featureless conformation that is similar to AM58–66GL9 presented by HLA-A*0201. In contrast with IAV, the sequence around residues 55–70 of IBV M1 does not contain an NES. Our comparative study on IBVs and IAVs provides new insights into the immune and evolution characteristics of IBVs and may shed light on vaccine development for influenza viruses.
Rabbits are pivotal domestic animals for both the economy and as an animal model for human diseases. A large number of rabbits have been infected by rabbit hemorrhagic disease virus (RHDV) in natural and artificial pandemics in the past. Differences in presentation of antigenic peptides by polymorphic major histocompatibility complex (MHC) molecules to T-cell receptors (TCR) on T lymphocytes are associated with viral clearance in mammals. Herein, we screened and identified a series of peptides derived from RHDV binding to the rabbit MHC class I molecule, RLA-A1. The small, hydrophobic B and F pockets of RLA-A1 capture a peptide motif analogous to that recognized by human class I molecule HLA-A*0201, with more restricted aliphatic anchors at P2 and PΩ positions. Meanwhile, the rabbit molecule is featured with an uncommon residue combination of Gly53, Val55 and Glu56, making the 310 helix and the loop between the 310 and α1 helices closer to the α2 helix. A wider A pocket in RLA-A1 can induce a special conformation of the P1 anchor and may play a pivotal role in peptide assembly and TCR recognition. Our study broadens the knowledge on T-cell immunity in domestic animals and also provides useful insights for vaccine development to prevent infectious diseases in rabbits. IMPORTANCE We screened rabbit MHC class I RLA-A1-restricted peptides from the capsid protein VP60 of Rabbit haemorrhagic disease virus (RHDV) and determined the structures of RLA-A1 complexed with three peptides, VP60-1, VP60-2 and VP60-10. From the structures, we found that the peptide binding motifs of RLA-A1 are extremely constraining. Thus, there is a generally restricted peptide selection for RLA-A1 compared to human HLA-A*0201. In addition, uncommon residues Gly53, Val55 and Glu56 of RLA-A1 are located between 310 helix and α1 helix which makes the steric position of 310 helix in RLA-A1 much closer to the α2 helix than other mammalian MHC class I molecules. This special conformation between 310 helix and α1 helix plays a pivotal role in rabbit MHC class I assembly. Our results provide new insights into MHC class I molecule assembly and peptide presentation of domestic mammals. Furthermore, these data also broaden our knowledge on T-cell immunity in rabbits and may also provide useful information for vaccine development to prevent infectious diseases in rabbits.
Asian countries have shown remarkable progress in financial inclusion and have become the world's fastest-growing regions. However, the financial inclusion-human health nexus has not received much attention. This study contributes to the empirical literature by examining the effect of financial inclusion on population health using panel data from Asian countries from 2007 to 2019. Population health is measured by death rate and life expectancy at birth. Our study finding shows that digital financial inclusion increases life expectancy but decreases the death rate in Asia. At the same time, financial inclusion positively impacts life expectancy and has a negative impact on the death rate in Asia. Finding also suggests that Internet users, GDP, and FDI have improved population health by increasing life expectancy and decreasing the death rate. The results suggest some essential policy implications.
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