Biology subjects

Cortes, F. H.

Publications and source records attributed to Cortes, F. H..

4 recordsLinked to original sources

bioRxiv2024

Identification of immunogenic and cross-reactive chikungunya virus-specific CD4+ T cell epitopes in chronic chikungunya viral arthritic disease in humans

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic chikungunya virus disease (CHIKVD) marked by persistent debilitating arthralgia. At present, the exact cause of chronic CHIKVD is not understood, and in humans, the targets of CD4+ T cells in CHIKV are currently unknown. Here, by stimulating peripheral blood mononuclear cells (PBMCs) collected from patients suffering from chronic CHIKVD with peptides spanning the entire CHIKV genome, we provide a comprehensive landscape of CHIKV CD4+ T cell epitopes. We identified 123 novel CD4+ T cell epitopes and three immunodominant regions in E1, nsP1 and CP proteins. The immunodominance of these E1, nsP1 and CP regions was mapped to optimal epitopes, characterized by the capacity to bind to many common HLA class II allelic variants. In addition, we designed and validated a new CHIKV-specific CD4+ T cell epitope megapool, spanning both structural and non-structural proteins, which can be a useful tool to study CHIKV-specific T cell responses in small blood volumes, typically available in pediatric or clinical samples. Finally, by in silico assessment of the conservation of the CHIKV proteome in a diverse set of alphaviruses, we defined CHIKV epitopes conserved across arthritogenic and encephalitic viruses. Overall, our work is the first to identify CD4+ T cell targets of CHIKV in humans, expanding our capacity to study the role of T cells in CHIKV pathogenesis and mapping targets of alphaviruses for vaccine design.

immunology↗

bioRxiv2023

Chikungunya-virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans

Chikungunya virus (CHIKV) is a mosquito-borne re-emerging viral infection that can cause chronic chikungunya viral arthritic disease (CHIKVD), which is characterized by incapacitating arthralgia and inflammation that can last for months to years following infection. Despite CHIKV outbreaks occurring worldwide and several vaccines currently in development, immune responses to CHIKV in humans remains largely understudied, and targets of T cell response are currently unknown. In this study, we tested peripheral blood mononuclear cells (PBMCs) collected from patients diagnosed with CHIKV infection during the 2014-2015 outbreak in Colombia against pools of overlapping peptides sequentially spanning each CHIKV protein. Using high-resolution flow cytometry, we detected robust CHIKV-specific CD4+, but not CD8+ T cell responses, in these patients. Patients still experiencing disease symptoms six years after infection displayed significantly stronger CHIKV- specific CD4+ T cell responses against nsP1, nsP2 and E2 proteins, compared to patients that resolved the infection. CHIKV-specific CD4+ T cells in symptomatic patients displayed a significantly lower Th1 CD4+ helper T cell responses and were enriched within the Th17 CD4+ helper subset, identifying tumor necrosis factor-alpha (TNF) as the predominantly produced cytokine. In conclusion, this study comprehensively characterizes the T cell response against CHIKV in humans during the chronic phase and provides insights into the role of T cells and possible treatment of CHIKVD.

immunology↗

bioRxiv2022

Humoral and cellular immune memory to four COVID-19 vaccines

Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike--specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though memory CD8+ T cells were only detectable in 60-67% of subjects at 6 months. Ad26.COV2.S was not the strongest immunogen by any measurement, though the Ad26.COV2.S T cell, B cell, and antibody responses were relatively stable over 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in neutralizing antibodies, while memory T cells and B cells were comparatively stable over 6 months. These results of these detailed immunological evaluations may also be relevant for vaccine design insights against other pathogens.

immunology↗

bioRxiv2019

HIV-1 controllers exhibit an enhanced antiviral state characterized by overexpression of p21 and MCPIP1

Some multifunctional cellular proteins, as the monocyte chemotactic protein-induced protein 1 (MCPIP1) and the cyclin-dependent kinase inhibitor p21, have also shown to be able to modulate the cellular susceptibility to the human immunodeficiency virus type 1 (HIV-1). Several studies described that p21 is expressed at high levels ex vivo in cells from individuals who naturally control HIV-1 replication (HIC). The expression level of MCPIP1 in HIC was never described before, but a recent study in a model of renal carcinoma cells showed that MCPIP1 overexpression was associated with an increase of both p21 transcripts and proteins levels. Here, we explored the potential associations between MCPIP1 and p21 expression, as well as with cellular activation in HIC, sustaining undetectable (elite controllers - EC) or low (viremic controllers - VC) viral loads. We found a selective upregulation of MCPIP1 and p21 mRNA levels in PBMC from HIC compared with both ART- suppressed and HIV-negative control groups (P [≤] 0.02) and a strong positive correlation (r [≥] 0.57; P [≤] 0.014) between expressions of both transcripts independently of the VL, treatment condition and HIV status. The mRNA levels of p21, but not of MCPIP1, were positively correlated with activated CD4+ T cells levels in HIC and EC (r [≥] 0.53; P [≤] 0.017). In relation to the monocyte activation, the mRNA levels of both p21 (r = 0.74; P = 0.005) and MCPIP1 (r = 0.58; P = 0.040) were positively correlated with plasmatic levels of sCD14 only in EC. Multivariate analysis confirmed the association between MCPIP1 and p21 mRNA levels, and between the latter with the frequency of activated CD4+ T cells. These data show for the first time the simultaneous overexpression and positive correlation of MCPIP1 and p21 transcripts in the setting of natural suppression of HIV-1 replication in vivo. The positive correlation between MCPIP1 and p21 transcripts supports a common regulatory pathway connecting these multifunctional host factors and a possible synergistic effect on HIV-1 replication control. Pharmacological manipulation of these cellular proteins may open novel therapeutic perspectives to prevent HIV-1 replication and disease progression.

immunology↗