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The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p

Revisión This article reviews the main discoveries achieved by transcriptomic approaches on HIV controller (HIC) and long-term non-progressor (LTNP) individuals, who are able to suppress HIV replication and maintain high CD4+ T cell levels, respectively, in the absence of antiretroviral therapy. Different studies using high throughput techniques have elucidated multifactorial causes implied in natural control of HIV infection. Genes related to IFN response, calcium metabolism, ribosome biogenesis, among others, are commonly differentially expressed in LTNP/HIC individuals. Additionally, pathways related with activation, survival, proliferation, apoptosis and inflammation, can be deregulated in these individuals. Likewise, recent transcriptomic studies include high-throughput sequencing in specific immune cell subpopulations, finding additional gene expression patterns associated to viral control and/or non-progression in immune cell subsets. Herein, we provide an overview of the main differentially expressed genes and biological routes commonly observed on immune cells involved in HIV infection from HIC and LTNP individuals, analyzing also different technical aspects that could affect the data analysis and the future perspectives and gaps to be addressed in this field. This study was funded by a fellowship from GILEAD Sciences (GLD18/00090), Instituto de Salud Carlos III (PI19CIII/00004), and has been conducted within the Spanish AIDS Research Network (RIS), funded by Instituto de Salud Carlos III (Plan Estatal de I+D+I 2013-2016) and co-funded by European Regional Development Fund (ERDF) "A way to build Europe" (RD16CIII/0002/0001). RA-S was supported by the Ministry of Innovation, Science and Universities predoctoral funding (FPU18/05527) Sí

Different phenotypes exhibiting no evidences of disease progression have been described in ART-naïve HIV-1 positive individuals. Long-term non progressors (LTNP) and elite controllers (EC) are low frequent examples of immunological and virological control in HIV-1 positive subjects, respectively. The combination of both phenotypes is even less frequent and studied despite being considered as models of HIV-1 functional cure. A multicenter, prospective study in retrospect including clinical and epidemiological data collected from 313 LTNP of 21 Spanish hospitals was carried out. LTNPs maintaining CD4+ T cell counts over 500 cells/µl and viral loads (VL) under 10,000 copies/mL for at least 10 years in the absence of antiretroviral therapy were followed for a median of 20.8 years (IQR = 15.6-25.5). A 52.1% were considered EC (undetectable VL) and LTNP (EC-LTNP) and a total of 171 (54.8%) and 42 (13.5%) out of the 313 participants maintained LTNP status for at least 20 and 30 years, respectively. EC-LTNP showed lower CD4+ T cell count loss (9.9 vs 24.2 cells/µl/year), higher CD4/CD8 ratio (0.01 vs - 0.09 in ratio), and lesser VL increase (no increase vs 197.2 copies/mL/year) compared with LTNPs with detectable VL (vLTNP). Survival probabilities for all-cause mortality at 30 years from HIV + diagnosis were 0.90 for EC-LTNP and 0.70 for vLTNP (p = 2.0 × 10-3), and EC-LTNP phenotype was the only factor associated with better survival in multivariate analyses (HR = 0.28; 95% CI 0.10-0.79). The probability to preserve LTNP status at 30 years was 0.51 for EC-LTNP and 0.18 for vLTNP (p

Factor de impacto: 4,242 Q1 Long-term non-progressors (LTNP) and elite controllers (EC) represent spontaneous natural models of efficient HIV-1 response in the absence of treatment. The main purposes of this work are to describe the miRNome of HIV-1 infected patients with different extreme phenotypes and identify potentially altered pathways regulated by differentially expressed (DE) miRNAs. The miRNomes from peripheral blood mononuclear cells (PBMCs) of dual phenotype EC-LTNP or LTNP with detectable viremia and HIV-infected patients with typical progression before and after treatment, were obtained through miRNA-Seq and compared among them. The administration of treatment produces 18 DE miRNAs in typical progressors. LTNP condition shows 14 DE miRNA when compared to typical progressors, allowing LTNP phenotype differentiation. A set of four miRNAs: miR-144-3p, miR-18a-5p, miR-451a, and miR-324 is strongly downregulated in LTNP and related to protein regulation as AKT, mTOR, ERK or IKK, involved in immune response pathways. Deregulation of 28 miRNA is observed between EC-LTNP and viremic-LTNP, including previously described anti-HIV miRNAs: miR-29a, associated with LTNP phenotype, and miR-155, targeting different pre-integration complexes such as ADAM10 and TNPO3. A holistic perspective of the changes observed in the miRNome of patients with different phenotypes of HIV-control and non-progression is provided. This study has been conducted within the Spanish AIDS Research Network (RIS), funded by Instituto de Salud Carlos III (Plan Estatal de I+D+I 2013-2016) and co-funded by European Regional Development Fund (ERDF) “A way to build Europe” (RD12/0017/0015 and RD16CIII/0002/0001 projects), and the European Union’s Horizon 2020 Research and Innovation Programme under grant number 681137. The HIV BioBank, integrated in the Spanish AIDS Research Network, is partially funded by the RD16/0025/0019 project as part of the Plan Nacional R + D + I and cofinanced by ISCIII- Subdirección General de Evaluación and el Fondo Europeo de Desarrollo Regional (FEDER). R.A.-S. was supported by the Ministry of Innovation, Science and Universities predoctoral funding (FPU18/05527) and H.E.T.-T. by the ISCIII-PFIS predoctoral program (FI14CIII/00014). Sí

Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with sero-negative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and –A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads, Instituto de Salud Carlos III from the Spanish Ministry of Health, through Red Temática de Investigación Cooperativa en SIDA (RIS) [G03/173(2), PI050528 and RD06/0006/0033 to MDV, RD06/0006/0035 and RD12/0017/0037 to the HIV BioBank, and C03/173 and RD12/0017/0018 to CoRIS], cofinanced by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER), and also financed by Plan Nacional I+D+I from the Spanish Ministry of Science and Technology [SAF2007-60934, SAF2010-18917 and SAF2013-48754-C2-1-R to MDV], by Instituto de Salud Carlos III [Intrasalud PI12/0056 to JA] and by Fundación para la Investigación y Prevención del SIDA en España (FIPSE) [to HIV Biobank]. Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO