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Sökning: WFRF:(Xue Yintong)

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1.
  • Marcotte, Harold, et al. (författare)
  • Conversion of monoclonal IgG to dimeric and secretory IgA restores neutralizing ability and prevents Infection of Omicron lineages
  • 2024
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 121:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previ- ously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot suffi- ciently boost the mucosal secretory IgA response in uninfected individuals, particu- larly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgAl antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibod- ies, dimeric and secretory IgAl antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgAl form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secre- tory IgA delivered by nasal administration may potentially be exploited for the treatment Iand prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.
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2.
  • Marcotte, Harold, et al. (författare)
  • Immunity to SARS-CoV-2 up to 15 months after infection
  • 2022
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Information concerning the longevity of immunity to SARS-CoV-2 following natural infection may have considerable implications for durability of immunity induced by vaccines. Here, we monitored the SARS-CoV-2 specific immune response in COVID-19 patients followed up to 15 months after symptoms onset. Following a peak at day 15-28 postinfection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Compared to G614, plasma neutralizing titers were more than 8-fold lower against variants Beta, Gamma, and Delta. SARS-CoV-2-specific memory B and T cells persisted in the majority of patients up to 15 months although a significant decrease in specific T cells, but not B cells, was observed between 6 and 15 months. Antiviral specific immunity, especially memory B cells in COVID-19 convalescent patients, is long-lasting, but some variants of concern may at least partially escape the neutralizing activity of plasma antibodies.
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3.
  • Sherina, Natalia, et al. (författare)
  • Persistence of SARS-CoV-2-specific B and T cell responses in convalescent COVID-19 patients 6-8 months after the infection
  • 2021
  • Ingår i: Med. - : Elsevier BV. - 2666-6340. ; 2:3, s. 281-295
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Monitoring the adaptive immune responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection provides useful information for the development of vaccination strategies against this virus and its emerging variants. We thus profiled the serum anti-SARS-CoV-2 antibody (Ab) levels and specific memory B and T cell responses in convalescent coronavirus disease 2019 (COVID-19) patients.Methods: A total of 119 samples from 88 convalescent donors who experienced mild to critical disease were tested for the presence of elevated anti-spike and anti-receptor binding domain Ab levels over a period of 8 months. In addition, the levels of SARS-CoV-2 neutralizing Abs and specific memory B and T cell responses were tested in a subset of samples.Findings: Anti-SARS-CoV-2 Abs were present in 85% of the samples collected within 4 weeks after the onset of symptoms in COVID-19 patients. Levels of specific immunoglobulin M (IgM)/IgA Abs declined after 1 month, while levels of specific IgG Abs and plasma neutralizing activities remained relatively stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG Abs were still present, although at a significantly lower level, in 80% of the samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B and T cell responses developed with time and were persistent in all of the patients followed up for 6-8 months.Conclusions: Our data suggest that protective adaptive immunity following natural infection of SARS-CoV-2 may persist for at least 6-8 months, regardless of disease severity. Development of medium- or long-term protective immunity through vaccination may thus be possible.
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4.
  • Xue, Yintong (författare)
  • Glucocorticoid in T cell differentiation
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Thymocytes differentiate into mature T cells with an immunological restriction for self major histocompatibility complex (MHC) antigens. Cells that do not recognize self MHC expressed on thymic epithelial cells (TEC) die by a rapid induction of apoptosis (default selection). Auto-reactive cells that recognize MHC presented endogenous peptides on bone-marrow derived antigen presenting cells also die by apoptosis (negative selection). Default selection accounts for the major loss of developing thymocytes out of which only a few percent develop into mature peripheral T cells. The present thesis deals with some aspects of thymic selection mechanisms with particular focus on the potential role of glucocorticoids (GC) in this process. GCs have earlier been shown to potently induce apoptosis in immature CD4+/CD8+ thymocytes. We have found that the GC receptor (GR) antagonist RU486 have an inhibitory effect in two model systems for thymic negative selection. In DO11.10 transgenic mice, in which the TCR transgene recognize an OVA derived peptide presented by the I-Ad MHC class II molecule, RU486 completely inhibited thymic apoptosis induced by peptide treatment (Paper I). In normal mice treated with the anti-CD3 mAb 2C 11, RU486 was earlier found to partially inhibit thymic apoptosis and this was now found to be dependent on the Fc domain of the mAb (Paper II). In untreated DO11.10 mice the TCR transgene was found to mediate a positive selection effect, correlating with a low expression of rnRNA for the nuclear receptor Nur77 (Paper IV). On further analysis of thymocytes from DO11.10 mice, these cells were found to be comparatively resistant to corticosterone (CS) in vitro and to contain reduced levels of GR as well as an increased expression of CD28 and increased DNA binding activity of transcription factors AP-1 and NFkB (Paper V). Based on our results, and some earlier publications, we postulated that TEC might secrete GC. This was tested by a reporter cell system in which COS cells, containing GR and GRE upstream of a reporter gene, were co-cultivated with explanted TEC in vitro (Paper III). TEC were found to generate a clear, specific signal in this system. I discuss the potential role of GC for default, and for different types of negative selection in thymus in relation to our own findings.
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5.
  • Zuo, Fanglei, et al. (författare)
  • Heterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 Omicron variant
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The recent emergence of the Omicron variant has raised concerns on vaccine efficacy and the urgent need to study more efficient vaccination strategies. Here we observed that an mRNA vaccine booster in individuals vaccinated with two doses of inactivated vaccine significantly increased the plasma level of specific antibodies that bind to the receptor-binding domain (RBD) or the spike (S) ectodomain (S1 + S2) of both the G614 and the Omicron variants, compared to two doses of homologous inactivated vaccine. The level of RBD- and S-specific IgG antibodies and virus neutralization titers against variants of concern in the heterologous vaccination group were similar to that in individuals receiving three doses of homologous mRNA-vaccine or a boost of mRNA vaccine after infection, but markedly higher than that in individuals receiving three doses of a homologous inactivated vaccine. This heterologous vaccination regime furthermore significantly enhanced the RBD-specific memory B cell response and S1-specific T cell response, compared to two or three doses of homologous inactivated vaccine. Our study demonstrates that mRNA vaccine booster in individuals vaccinated with inactivated vaccines can be highly beneficial, as it markedly increases the humoral and cellular immune responses against the virus, including the Omicron variant.
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