Additional file 8 of Higher plasma levels of thymosin-α1 are associated with a lower waning of humoral response after COVID-19 vaccination: an eight months follow-up study in a nursing home

Additional file 8. Detailed methodology.Consejería de Transformación Económica, Industria, Conocimiento y Universidades Instituto de Salud Carlos III Consejería de Salud y Familias, Junta de AndalucíaPeer reviewe

Additional file 2 of Higher plasma levels of thymosin-α1 are associated with a lower waning of humoral response after COVID-19 vaccination: an eight months follow-up study in a nursing home

Additional file 2: Supplementary Table 1. Demographical and anthropometrics characteristics of the study population.Consejería de Transformación Económica, Industria, Conocimiento y Universidades Instituto de Salud Carlos III Consejería de Salud y Familias, Junta de AndalucíaPeer reviewe

Additional file 6 of Higher plasma levels of thymosin-α1 are associated with a lower waning of humoral response after COVID-19 vaccination: an eight months follow-up study in a nursing home

Additional file 6: Supplementary Fig. 3. Correlations among Log of anti-S antibody titers at all different study points.Consejería de Transformación Económica, Industria, Conocimiento y Universidades Instituto de Salud Carlos III Consejería de Salud y Familias, Junta de AndalucíaPeer reviewe

Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients

[Introduction] Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients.[Methods] To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response.[Results] Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses.[Discussion] In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.This study was supported by a grant from the Fondo de Investigación Sanitaria (FIS/PI21/00357), which is co-founded by Fondos Europeos para el Desarrollo Regional (FEDER) “Una manera de hacer Europa”. VG-R, IO-M and AB-R were supported by Instituto de Salud Carlos III (CD19/00143, FI19/00298 and CM19/00051, respectively). MP-B was supported by the Consejería de Transformación Económica, Industria, Conocimiento y Universidades [DOC_01646 to MP-B] and YP was supported by the Consejería de Salud y Familias of Junta de Andalucía through the “Nicolás Monardes” [RC-0006-2021].Peer reviewe

Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. (HR 3.40; 95% CI, 1.39–8.32).

Relationship between Regulatory T Cells and Immune Activation in Human Immunodeficiency Virus-Infected Patients Interrupting Antiretroviral Therapy

Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV) disease progression. Whether CD4+CD25+ regulatory T cells (Tregs) are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs) and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART). Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI) (ANRS 116). Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12) of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r = −0.519). Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p = 0.029); absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p = 0.031). At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI

A Low T Regulatory Cell Response May Contribute to Both Viral Control and Generalized Immune Activation in HIV Controllers

HIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers) often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell activation levels, potentially contributing to T cell dysfunction, CD4+ T cell depletion, and non-AIDS morbidity. We hypothesized that a weak T regulatory cell (Treg) response might contribute to the control of viral replication in HIV controllers, but might also contribute to generalized immune activation, contributing to CD4+ T cell loss. To address these hypotheses, we measured frequencies of activated (CD38+ HLA-DR+), regulatory (CD4+CD25+CD127dim), HIV-specific, and CMV-specific T cells among HIV controllers and 3 control populations: HIV-infected individuals with treatment-mediated viral suppression (ART-suppressed), untreated HIV-infected “non-controllers” with high levels of viremia, and HIV-uninfected individuals. Despite abnormally high T cell activation levels, controllers had lower Treg frequencies than HIV-uninfected controls (P = 0.014). Supporting the propensity for an unusually low Treg response to viral infection in HIV controllers, we observed unusually high CMV-specific CD4+ T cell frequencies and a strong correlation between HIV-specific CD4+ T cell responses and generalized CD8+ T cell activation levels in HIV controllers (P≤0.001). These data support a model in which low frequencies of Tregs in HIV controllers may contribute to an effective adaptive immune response, but may also contribute to generalized immune activation, potentially contributing to CD4 depletion

Detectable viral load aggravates immunosenescence features of CD8 T-cell subsets in vertically HIV-infected children

Background: CD8 T cells are crucial in the immune responses against HIV infection, but HIV-infected adults suffer a naive CD8 T-cell depletion and accelerated senescence caused by chronic antigen stimulation. Although HIV-infected children preserve a better immune reconstitution capacity their CD8 responses are defective. We wanted to know, whether HIV vertical transmission produces a premature aging of the CD8 population due to antigen exposition to HIV from birth and persistent chronic activation. Methods: We conducted a multicentre cross-sectional study that compared vertically HIV-infected children with detectable (viremic) or undetectable (aviremic) viral load and age-matched healthy children. Using multiparameter flow cytometry, we studied within the CD8 population the frequencies of naive, memory, effector memory (effector memory), and TemRA subsets and measured markers of senescence, activation, and proliferation in these cells. Results: We found that naive subset in viremic children was markedly decreased and had a replicative senescence phenotype. Furthermore, viremic children showed increased frequencies of memory, TEM and TemRA CD8 T cells, with a more activated and replicative senescence phenotype. We found that HIV-infected children with undetectable viral load have an increased senescence in memory and effector CD8 T cells, but the frequencies and phenotype of the CD8 subsets analyzed are comparable to healthy children. Conclussions: Our study shows that CD8 T cells of HIV-infected children have a more senescent phenotype when compared with age-matched healthy children. Interestingly enough, our results support the importance of maintaining undetectable viral load in HIV-infected children to avoid the premature ageing and dysfunction of CD8 T cells. © 2012 by Lippincott Williams & Wilkins.Peer Reviewe

Maraviroc contributes to the restoration of the homeostasis of regulatory T-cell subsets in antiretroviral-naive HIV-infected subjects.

Regulatory T (Treg) cells comprise different functional subsets with different CCR5 expression. Treg homeostasis is disrupted by HIV but the effect of treatment has barely been explored. In a longitudinal design, we compared the effect of a maraviroc-containing (n = 9) or sparing (n = 12) therapy in antiretroviral-naive HIV-positive participants on peripheral FoxP3(low) CD45RA(+) (nTreg), FoxP3(high) CD45RA(-) (eTreg) and FoxP3(low) CD45RA(-) (non-Treg) cells. Maraviroc significantly reduced all subsets in the short-term and, except for nTreg cells, also normalized them in the long-term. The correlation between eTreg cells and CD4 counts, lost before treatment, was only restored by maraviroc. The differential effect of maraviroc on Treg subsets contributes to understanding its immunomodulatory effects

Severe immune dysregulation affects CD4 +CD25 hiFoxP3 + regulatory T cells in HIV-infected patients with low-level CD4 T-Cell repopulation despite suppressive highly active antiretroviral therapy

We hypothesized that CD4 +CD25 hiFoxP3 + regulatory T cells (Tregs) could be involved in the high immune activation existing in patients with low-level CD4 T-cell repopulation under suppressive high active antiretroviral therapy (hereafter, >LLR patients>). Sixteen LLR patients, 18 human immunodeficiency virus (HIV)-infected controls (hereafter, >HIV controls>), and 16 healthy subjects were included. The frequency of CD4 +CD25 hiFoxP3 + and HIV-specific Treg suppressive function were assessed. Relationships between Treg and CD4/CD8 activation (HLA-DR/CD38) and the frequency of naive CD4 T-cells were assessed. Low-level patients showed a higher Treg frequency but reduced HIV-specific immunosuppressive functions than HIV controls. Whereas in healthy subjects a strong negative correlation between Tregs and activated CD8 T cells emerged (r =-0.75, P <. 001), it appeared disrupted in both HIV-infected groups (r =-0.06 and P =. 83 for LLR patients; r =-0.11 and P =. 68 for and HIV controls). Nevertheless, in LLR patients, Tregs negatively correlated with naive CD4 T cells (r =-0.60, P =. 01), whereas there was no such correlation in HIV controls (r =-0.19, P =. 46) or healthy subjects (r =-0.10, P =. 73). Remarkably, a higher ratio of Tregs to naive CD4 T cells was observed in LLR patients than in HIV controls (P =. 001) and healthy subjects (P <. 001). We conclude that LLR patients have important alterations in immunoregulation involving CD4 +CD25 hiFoxP3 + Tregs. In this scenario, the role of Tregs seems to be more related to the control of the naive CD4 T-cell homeostatic proliferation, rather than to the immune activation. © 2012 The Author.Peer Reviewe