Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults.

The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30-45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30-45) as compared to NV(D0) (532vs398). Moreover, PV(D30-45) exhibited increased levels of Terminal Effector (CD45RA+CCR7-) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30-45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

An initial investigation of serum cytokine levels in patients with gadolinium retention / Uma investigação inicial dos níveis séricos de citocinas em pacientes com retenção de gadolínio

Abstract Objective: To determine whether individuals with proposed gadolinium deposition disease (GDD) have elevated serum levels of pro-inflammatory and pro-fibrotic cytokines, and whether specific cytokines are correlated with certain symptoms. Materials and Methods: Twenty-four participants recruited between May 2016 and June 2017 met GDD diagnostic criteria. The 64 control subjects provided serum samples before prophylactic flu vaccination. Serum cytokine levels were obtained with Luminex serum cytokine assay using eBiosciences/Affymetrix human 62-plex kits. Wilcoxon rank-sum tests were performed to assess the difference between the median fluorescence intensity values for the participants and the control group. Generalized linear models were built to evaluate the association between each cytokine of interest and selected participant symptoms. Results: Serum levels of 14 cytokines, including nine pro-inflammatory cytokines, were statistically significantly elevated compared to controls (p ≤ 0.05). Hypotheses regarding pro-fibrotic cytokines and cytokine links to specific symptoms' intensity were not confirmed. Conclusion: The statistically significantly elevated cytokines may be markers of susceptibility to GDD or agents of symptom induction. These findings suggest that individuals developing symptoms characteristic of GDD after a contrast-assisted magnetic resonance imaging should be studied to investigate whether gadolinium retention and elevated cytokines may be related to their symptoms.

Resumo Objetivo: Determinar se indivíduos com doença de deposição de gadolínio (DDG) apresentam níveis séricos elevados de citocinas pró-inflamatórias e pró-fibróticas e se citocinas específicas estão correlacionadas com determinados sintomas. Materiais e Métodos: Vinte e quatro participantes recrutados entre maio/2016 e junho/2017 cumpriram os critérios de diagnóstico de DDG. Amostras de soro de 64 indivíduos controles foram obtidas antes de vacinação profilática contra a gripe. Os níveis de citocinas séricas foram mensurados com o ensaio Luminex usando kits 62-plex humanos. Foram realizados testes de Wilcoxon para avaliar a diferença dos valores médios de intensidade de fluorescência entre os participantes e o grupo controle. Foram construídos modelos lineares generalizados para avaliar a associação entre cada citocina de interesse e os sintomas dos participantes selecionados. Resultados: Níveis séricos de 14 citocinas, incluindo 9 citocinas pró-inflamatórias, foram estatisticamente significantes em comparação aos controles (p ≤ 0,05). Hipóteses sobre as citocinas pró-fibróticas e associação das citocinas com a intensidade de sintomas específicos não foram confirmadas. Conclusão: Citocinas estatisticamente elevadas podem ser marcadores de suscetibilidade para DDG ou agentes de indução de sintomas. Esses achados sugerem que indivíduos que desenvolvem sintomas da DDG após ressonância magnética com contraste devem ser estudados para investigar se a retenção de gadolínio e citocinas elevadas podem estar relacionadas aos seus sintomas.