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 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

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

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

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

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

Dysregulation of iron metabolism modulators in virologically suppressed HIV-infected patients

[Background] Iron metabolism plays an essential role in cellular functions. Since virologically suppressed chronic HIV-infected subjects under effective antiretroviral treatment (ART) exhibit a persistent immune dysfunction that leads to comorbidities, iron homeostasis may be relevant in this context. We aimed to explore iron metabolism in virologically suppressed chronic HIV infected subjects under a successful ART.[Methods] In this retrospective study, traditional iron metabolism biomarkers (total iron, ferritin, transferrin, and transferrin saturation index), as well as soluble transferrin receptor (sTfR), hepcidin, and inflammatory markers were determined in virologically suppressed chronic HIV-infected subjects under at least 2 years of ART (HIV) who also had >350 CD4-T-cells/mm3 (N=92) from Spain. As controls, we collected non-HIV age-matched healthy donors (Young, N=25) and elderly subjects (>65 years old; Elderly; N=25). Additionally, an external group of non-HIV patients with ferritin<50 ng/mL diagnosed with absolute iron deficiency (Ferropenic group; N=84) was included. Comparisons between groups were performed using Kruskal-Wallis or Mann-Whitney U-tests, while associations between variables were explored by Spearman’s rho correlation coefficient.[Results] We selected samples from HIV-infected subjects (aged 42[34-47], 95% males), young age-matched (aged 40[30-58], 60% males), and elderly controls (aged 82[78-88], 100% males). Compared to both healthy (Young and Elderly) groups, HIV exhibited decreased iron, transferrin saturation, and sTfR, and increased ferritin, but similar hepcidin levels. Notably, associations between sTfR and iron (Young, r=-0.587, p=0.002; Elderly, r=-0.496, p=0.012) or transferrin saturation index (Young, r=-0.581, p=0.002; Elderly, r=-0.489, p=0.013) were negative in both controls while positive in HIV (r=0.464, p<0.0001 and r=0.421, p<0.0001, respectively). Moreover, the expected negative correlation between hepcidin and sTfR, observed in controls (Young, r=-0.533, p=0.006; Elderly, r=-0.473, p=0.017), was absent in HIV (r=0.082; p=0.438). Interestingly, the HIV inflammatory profile differed from the Elderly one, who despite their inflammaging-related profile, succeed in maintaining these associations. Furthermore, subjects from the ferropenic group (aged 42[32-51], 5% males), showing significantly lower levels of hepcidin and higher sTfR, as expected, reflected similar correlations as those Young and Elderly, in contrast to HIV.[Conclusions] Virologically suppressed chronic HIV-infected patients under successful ART exhibit altered levels of iron metabolism modulators suggesting a complex functional iron deficiency.This work was supported by grants from the Fondo de Investigación Sanitaria [FIS; PI18/01216 and PI21/00357] which is co-funded by Fondos Europeos para el Desarrollo Regional (FEDER) “Una manera de hacer Europa”, the Instituto de Salud Carlos III [FI19/00298 to VG-R, CM19/00051 to IO-M and CD19/00143 to AB-R], the Consejería de Transformación Económica, Industria, Conocimiento y Universidades [DOC_01646 to MP-B] and the Consejería de Salud y Familias of Junta de Andalucía through the “Nicolás Monardes” [C-0013-2017 to YMP]. The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Grant n° RD06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional I+D+i and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER)”. The RIS Cohort (CoRIS) was funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I+D+i and cofinanced by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER).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 FoxP3low CD45RA+ (nTreg), FoxP3high CD45RA– (eTreg) and FoxP3low 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.This work was supported by grants from the Fondo de Investigación Sanitaria (FIS; P11/02014), the Spanish AIDS Research Network of Excellence (RIS; RD12/0017/0029, RD12/0017/0037), the Ministerio de Sanidad, Política Social e Igualdad (EC11-520], the Fundación Progreso y Salud [PI-0081-2011], and Pfizer/ViiV Healthcare (grant numbers WS843473, WS2425049). Y.M. Pacheco was supported by the Fondo de Investigación Sanitaria through the “Miguel Servet” programs (CP07/00240, CPII13/00037), and by the Consejeria de Salud y Bienestar Social of Junta de Andalucia through the ‘Nicolas Monardes’ programme [C-0010/13]. E Ruiz-Mateos was supported by the Fondo de Investigación Sanitaria through the ‘Miguel Servet’ programme [CP08/0172]. M.R. Benhnia was supported by the Ministry of Economy and Competitiveness (Ramon y Cajal grant RYC-2010-07419)

Longitudinal age differences in humoral responses to the COVID-19 vaccine in the elderly are lost after the third dose

Nursing home residents constitute an especially frail population at a high risk for severe COVID-19 disease,1 mainly due to multiple comorbid conditions and immunesenescence.2 Hence, many countries have considered the administration of booster doses of vaccines due to the lower levels of anti-S IgG antibodies achieved by elderly adults after two doses of vaccine and a faster waning immunity thereafter.3 A recent work published in this journal by Dimeglio et al.,4 showing anti-SARS-CoV-2 antibodies before and after the third dose of the vaccine, reported that elderly adults achieved similar levels of anti-S IgG titers after the booster dose than those achieved by younger participants, shedding light on the benefit of the administration of such vaccine booster. Here, we present additional longitudinal data reinforcing this concept.This work was supported by the Instituto de Salud Carlos III through the project “PI21/00357” (Co-funded byEuropean Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). MMPB was supported by a postdoctoral contract from Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía (DOC_01646). ABR, IOM and VGR were supported by Instituto de Salud Carlos III (Sara Borrell program CD19/00143, Rio Hortega program CM19/00051, and PFIS program FI19/00298, respectively). YMP was supported by the Consejería de Salud y Familias of Junta de Andalucía through the ‘‘Nicolás Monardes’’ program (RC‐0006-2021).Peer reviewe

Differential alterations of the CD4 and CD8 T cell subsets in HIV-infected patients on highly active antiretroviral therapy with low CD4 t cell restoration

Objectives: This study examined the homeostatic parameters possibly related to HIV-infected patients who, despite being under suppressive highly active antiretroviral therapy (HAART), show low-level CD4 T cell repopulation (LLR). Methods: Twenty-one LLR individuals, 20 HIV-infected controls with satisfactory CD4 T cell repopulation (R) and 14 healthy subjects were studied. Markers related to activation, senescence and proliferation were analysed for both the CD4 and CD8 T cell subsets. Additionally, soluble CD14 (sCD14) and high-sensitivity C-reactive protein (hsCRP) were measured, and the CD34+ cells and the levels of interleukin-7 (IL-7) receptor were quantified. Results: The frequency of naive CD4 T cells from LLR patients was significantly reduced, and these cells showed increased expression of markers for activation, senescence and proliferation as compared with naive CD4 T cells from R patients. Naive CD8 T cells were also reduced when compared with those from R patients, but did not exhibit an altered phenotype. Moreover, frequencies of effector memory T cells were higher in LLR than R patients. No differences between LLR and R patients were observed for sCD14 levels, CD34+ cells and the IL-7 receptor, although LLR patients showed a tendency toward increased levels of hsCRP >2 μg/mL. Conclusions: Patients with low CD4 T cell restoration under suppressive HAART show significant alterations in T cell homeostasis that do not appear to be related to a reduction in haematopoietic progenitors. sCD14 levels were not specifically altered in these patients. Our results agree with our previously proposed model of premature immunosenescence in LLR patients and further describe homeostatic features associated with poor CD4 recovery. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.This work was supported by the Spanish AIDS Research Network of Excellence (RIS; Red de Investigación en SIDA) [RD06/0006/0021 to MMPB and RD06/0006/0035]; the Consejería de Salud of Junta de Andalucía [PI-0366/07]; the Fundación para la Investigación y la prevención del SIDA en España (FIPSE) [366884/07 to GML]; and the Fondos de Investigación Sanitaria (FIS) [P11/02014 and Miguel Servet Grants CP07/00240 to YMP and CP08/00172 to ERM].Peer Reviewe