Zedda L.,Novartis |
Forleo-Neto E.,Novartis |
Vertruyen A.,Sint Vincentius Ziekenhuis |
Raes M.,Kinderartsenassociatie |
And 9 more authors.
Pediatric Infectious Disease Journal | Year: 2015
Introduction: Annual seasonal influenza epidemics are particularly dangerous for the very young, the elderly and chronically ill individuals, in whom infection can cause severe morbidity, hospitalization and death. Existing, nonadjuvanted influenza vaccines exhibit a suboptimal immunogenicity and efficacy in immunologically naive subjects such as young children. Methods: This phase II, randomized clinical trial was conducted to evaluate the antibody and cell-mediated responses to a trivalent influenza vaccine administered without adjuvant (TIV) or adjuvanted with MF59 (ATIV) in previously nonvaccinated children less than 3 years of age. Results: The MF59-adjuvanted vaccine was well tolerated, and induced higher titers of hemagglutination inhibition antibodies able to recognize strains different from the one used in the vaccine (heterovariant) than TIV. The presence of the adjuvant MF59 induced a larger expansion of vaccinespecific CD4+ T cells. Interestingly, the adjuvant MF59 did not modify the cytokine profile of the elicited T cells, characterized by the production of IL-2 and TNF-α, and did not bias the response toward either Th1 or Th2. The advantage of ATIV over TIV was more pronounced for the virus strains that had not circulated in the years that preceded this study and for the heterovariant strains. Conclusion: These data highlight the relevant role played by the oil-inwater adjuvant MF59 in enhancing the immunogenicity of inactivated influenza vaccines in immunologically naive individuals. Copyright © 2014 by Lippincott Williams & Wilkins.
Lauwerys B.R.,Catholic University of Louvain |
Spertini F.,CHU Vaudois |
Lazaro E.,Bordeaux University Hospital Center |
Mariette X.,University Paris - Sud |
And 6 more authors.
Arthritis and Rheumatism | Year: 2013
Objective We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE. Methods We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 μg, 60 μg, 120 μg, or 240 μg of IFN-K or placebo in 28 women with mild to moderate SLE. Results IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers. Conclusion These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted. Copyright © 2013 by the American College of Rheumatology.
Dauby N.,Free University of Colombia |
Sartori D.,Free University of Colombia |
Kummert C.,ImmuneHealth |
Lecomte S.,Free University of Colombia |
And 4 more authors.
Journal of Infectious Diseases | Year: 2016
Background. Following primary human cytomegalovirus (HCMV) infection, the production of antibodies against envelope glycoprotein B (gB) is delayed, compared with production of antibodies against tegument proteins, and this likely reduces the control of HCMV dissemination. Methods. The frequency and the phenotype of gB-specific and tegument protein-specific B cells were studied in a cohort of pregnant women with primary HCMV infection. Healthy adults who had chronic HCMV infection or were recently immunized with tetanus toxoid (TT) were included as controls. Results. Primary HCMV infection was associated with high and similar frequencies of gB-specific and tegument protein-specific B cells following primary HCMV infection. During primary infection, tegument protein-specific B cells expressed an activated (CD21low) memory B-cell (MBC) phenotype. Activated MBCs were also induced by TT booster immunization, indicating that the expansion of this subset is part of the physiological B-cell response to protein antigens. In contrast, gB-specific B cells had a predominant classical (CD21+) MBC phenotype during both primary and chronic infections. Conclusions. The delayed production of gB-specific immunoglobulin G (IgG) during primary HCMV infection is associated with a limited induction of MBCs with effector potential. This novel mechanism by which HCMV may interfere with the production of neutralizing antibodies could represent a target for therapeutic immunization. © 2016 The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Huygens A.,Free University of Colombia |
Lecomte S.,Free University of Colombia |
Olislagers V.,Free University of Colombia |
Delmarcelle Y.,ImmuneHealth |
And 6 more authors.
Journal of Infectious Diseases | Year: 2015
Background. Cytomegalovirus (CMV) infection during fetal life causes severe symptoms and is associated with prolonged viral excretion. Previous studies reported low CD4+ T-cell responses to CMV infection in early life, contrasting with large responses of effector CD8+ T cells. The mechanisms underlying the defective CD4+ T-cell responses and the possible dissociation with CD8+ T-cell responses have not been clarified. Methods. The magnitude and the quality of the fetal CD8+ and CD4+ T-cell responses to CMV infection were compared to those of adults with primary or chronic infection. Results. In utero CMV infection induced oligoclonal expansions of fetal CD4+ and CD8+ T lymphocytes expressing a T-helper type 1 or Tc1 effector phenotype similar to that of adult CMV-specific cells. However, the effector cytokine responses and the polyfunctionality of newborn CD4+ and CD8+ T cells were markedly lower than those of adult cells. This reduced functionality was associated with a higher expression of the programmed death 1 inhibitory receptor, and blockade of this receptor increased newborn T-cell responses. Conclusions. Functional exhaustion limits effector CD4+ and CD8+ T-lymphocyte responses to CMV during fetal life. © 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Compte N.,Free University of Colombia |
Boudjeltia K.Z.,Free University of Colombia |
Vanhaeverbeek M.,Free University of Colombia |
De Breucker S.,Service de Geriatrie |
And 4 more authors.
PLoS ONE | Year: 2013
Background/Aim of the study: Low-grade systemic inflammation was suggested to participate to the decline of physiological functions and increased vulnerability encountered in older patients. Geriatric syndromes encompass various features such as functional dependence, polymorbidity, depression and malnutrition. There is a strong prevalence of cardiovascular diseases and related risk factors and chronic cytomegalovirus infections in the geriatric population. As these underlying conditions were proposed to influence the inflammatory state, the aim of this study was to assess their potential contribution to the association of geriatric syndromes with inflammatory parameters. Methodology: We recruited 100 subjects in the general population or hospitalized for chronic medical conditions (age, 23-96 years). We collected information on clinical status (medical history, ongoing comorbidities, treatments and geriatric scales), biological parameters (hematological tests, cytomegalovirus serology) and cytokines production (basal and alum-induced interleukin (IL)-1β and IL-6 levels). Using stepwise backward multivariate analyses, we defined which set of clinical and biological variables could be predictive for increased inflammatory markers. Principal Findings: We confirmed the age-associated increase of circulating IL-6 levels. In contrast to geriatric scales, we found history of cardiovascular diseases to be strongly associated for this parameter as for high IL-6 production upon ex vivo stimulation with alum. Conclusions: Association between low-grade inflammation and geriatric conditions could be linked to underlying cardiovascular diseases. © 2013 Compté et al.