Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

Longitudinal evaluation of the impact of immunosuppressive regimen on immune responses to COVID-19 vaccination in kidney transplant recipients.

International audienceImmunocompromised patients have a high risk of death from SARS-CoV-2 infection. Vaccination with an mRNA vaccine may protect these patients against severe COVID-19. Several studies have evaluated the impact of immune-suppressive drug regimens on cellular and humoral responses to SARS-CoV-2 variants of concern in this context. We performed a prospective longitudinal study assessing specific humoral (binding and neutralizing antibodies against spike (S) and T-lymphocyte (cytokine secretion and polyfunctionality) immune responses to anti-COVID-19 vaccination with at least two doses of BNT162b2 mRNA vaccine in stable kidney transplant recipients (KTR) on calcineurin inhibitor (CNI)- or belatacept-based treatment regimens. Fifty-two KTR−31 receiving CNI and 21 receiving belatacept—were enrolled in this study. After two doses of vaccine, 46.9% of patients developed anti-S IgG. Anti-spike IgG antibodies were produced in only 21.4% of the patients in the belatacept group, vs. 83.3% of those in the CNI group. The Beta and Delta variants and, more importantly, the Omicron variant, were less well neutralized than the Wuhan strain. T-cell functions were also much weaker in the belatacept group than in the CNI group. Renal transplant patients have an impaired humoral response to BNT162b2 vaccination. Belatacept-based regimens severely weaken both humoral and cellular vaccine responses. Clinically, careful evaluations of at least binding IgG responses, and prophylactic or post-exposure strategies are strongly recommended for transplant recipients on belatacept-based regimens

J Infect Dis

BACKGROUND: The EBL2001 phase 2 trial tested the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine in Europe. Safety and humoral immunogenicity assessments led to EU market authorization in 2020. Complementary analyses of immune responses are warranted to better characterize vaccine effects. METHODS: We conducted an ancillary study to analyze changes in the serum and cellular responses. Serum biomarkers of activation/inflammation were evaluated using a Luminex assay. Vaccine-elicited T cell responses and functions were evaluated assessing their phenotype, cytokine production, proliferation and cytotoxic potential. Integrated data analysis was performed through correlation and principal component analysis of serum biomarkers and cellular immune responses. RESULTS: Forty-eight volunteers were included. The Ad26.ZEBOV, MVA-BN-Filo vaccine elicited: i) serum increase of inflammatory/activation markers mainly at 1 day after the Ad26.ZEBOV vaccine; ii) durable EBOV-specific T cell proliferation and CD8+ T cells exhibiting a cytotoxic phenotype after Ad26.ZEBOV prime, after MVA-BN-Filo boost and 6 months post vaccination. Integrated analysis revealed correlations between: i) EBOV-specific CD8+ T cell proliferation and cytotoxic phenotype; ii) high EBOV-specific CD8+ T cell cytotoxic phenotype and low inflammatory marker IL-8 at day 1 post vaccination. DISCUSSION: This study provides unique insights into the in vivo contribution of proliferation/cytotoxic CD8+ T cells and inflammation to the Ad26.ZEBOV, MVA-BN-Filo vaccine-induced potency.Initiative for the creation of a Vaccine Research Institut

T-cell and Transcriptomic Responses to Prime-boost Strategies of 3 HIV Vaccines(MVA HIV-B; LIPO-5; GTU-MultiHIV B)-ANRS/INSERM VRI01 Trial

International audienc

T-cell and Transcriptomic Responses to Prime-boost Strategies of 3 HIV Vaccines(MVA HIV-B; LIPO-5; GTU-MultiHIV B)-ANRS/INSERM VRI01 Trial

International audienc

T Cell Immunogenicity, Gene Expression Profile, and Safety of Four Heterologous Prime-Boost Combinations of HIV Vaccine Candidates in Healthy Volunteers: Results of the Randomized Multi-Arm Phase I/II ANRS VRI01 Trial

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Neutrophil Activation and Immune Thrombosis Profiles Persist in Convalescent COVID-19

International audiencePurpose Following a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies the persistence of symptoms months after the resolution of acute COVID-19. Methods We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole blood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6 months following hospital discharge. Results We observed persistent abnormalities until month 6 marked by (i) high serum levels of monocyte/macrophage and endothelial activation markers, chemotaxis, and hematopoietic cytokines; (ii) a high frequency of central memory CD4 + and effector CD8 + T cells; (iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies; and (iv) an upregulation of genes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation, and RUNX1 signaling. We identified a “core gene signature” associated with a history of thrombotic events, with upregulation of a set of genes involved in neutrophil activation, platelet, hematopoiesis, and blood coagulation. Conclusion The lack of restoration of gene expression to a normal profile after up to 6 months of follow-up, even in asymptomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose preventive measures