Recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein (rVSV-EBOV), a new Ebola vaccine.

Ebola virus (EBOV) causes outbreaks of lethal febrile illness in Africa, the largest of which resulted in over 11,000 deaths and represented a global public health threat. A new biomedical countermeasure, the recombinant vesicular stomatitis virus expressing EBOV glycoprotein (rVSV-EBOV) has been licensed (Ervebo; Merck & Co.). rVSV-EBOV is a replicative viral vaccine engineered to express EBOV antigen. Following rapid development stimulated by the large West African epidemic, an open-label, cluster-randomized ring vaccination trial called Ebola Ça Suffit! in Guinea and Sierra Leone demonstrated strong efficacy. The vaccine has a good safety profile, but is associated with self-limited arthritis and rash in a minority of recipients. rVSV-EBOV is highly immunogenic after a single intramuscular dose with antibody titers persisting for at least 2 years. In the recent outbreak in the Democratic Republic of the Congo, rVSV-EBOV was administered to more than 300,000 individuals and may have contributed, at least in part, to controlling the epidemic.

Endothelial activation is associated with intestinal epithelial injury, systemic inflammation and treatment regimen in children living with vertically acquired HIV-1 infection.

BACKGROUND: Premature development of cardiovascular disease in children living with HIV-1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH. METHODS: This was a cross-sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation-Canadian Child Cure Cohort (EPIC4 ) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury [intestinal fatty acid binding protein-1 (IFABP)], systemic inflammation [tumour necrosis factor (TNF) and interleukin-6 (IL-6)] and endothelial activation [angiopoietin-2 (Ang2), soluble vascular endothelial growth factor-1 (sVEGFR1) and soluble endoglin (sEng)] were quantified by enzyme-linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways. RESULTS: Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P < 0.001 for all correlations). An endothelial activation index, derived by factor analysis of the three endothelial biomarkers, was correlated with TNF (ρ = 0.47, P < 0.001), IL-6 (ρ = 0.60, P < 0.001) and intestinal fatty acid binding protein-1 (ρ = 0.67, P < 0.001). Current or past treatment with ritonavir-boosted lopinavir (LPV/r) was associated with endothelial activation (odds ratio = 5.0, 95% CI: 1.7-17, P = 0.0020). CONCLUSIONS: Endothelial activation is prevalent in CLWH despite viral suppression with combination ART and is associated with intestinal epithelial injury, systemic inflammation and treatment with LPV/r.