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Dive into the research topics where Emmanuel Hanon is active.

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Featured researches published by Emmanuel Hanon.


Immunity | 2000

Fratricide among CD8+ T Lymphocytes Naturally Infected with Human T Cell Lymphotropic Virus Type I

Emmanuel Hanon; Jane C. Stinchcombe; Mineki Saito; Becca Asquith; Graham P. Taylor; Yuetsu Tanaka; Jonathan Weber; Gillian M. Griffiths; Charles R. M. Bangham

Infection and gene expression by the human T lymphotropic virus type I (HTLV-I) in vivo have been thought to be confined to CD4(+) T lymphocytes. We show here that, in natural HTLV-I infection, a significant proportion of CD8(+) T lymphocytes are infected by HTLV-I. Interestingly, HTLV-I-specific but not Epstein-Barr virus-specific CD8(+) T lymphocytes were shown to be infected. Furthermore, HTLV-I protein expression in naturally infected CD8(+) T lymphocytes renders them susceptible to fratricide mediated by autologous HTLV-I-specific CD8(+) T lymphocytes. Fratricide among virus-specific CTLs could impair the immune control of HTLV-I and possibly other lymphotropic viruses.


PLOS ONE | 2008

Broad Clade 2 Cross-Reactive Immunity Induced by an Adjuvanted Clade 1 rH5N1 Pandemic Influenza Vaccine

Isabel Leroux-Roels; Roger Bernhard; Pascal P Gerard; Mamadou Dramé; Emmanuel Hanon; Geert Leroux-Roels

Background The availability of H5N1 vaccines that can elicit a broad cross-protective immunity against different currently circulating clade 2 H5N1 viruses is a pre-requisite for the development of a successful pre-pandemic vaccination strategy. In this regard, it has recently been shown that adjuvantation of a recombinant clade 1 H5N1 inactivated split-virion vaccine with an oil-in-water emulsion-based adjuvant system also promoted cross-immunity against a recent clade 2 H5N1 isolate (A/Indonesia/5/2005, subclade 2.1). Here we further analyse the cross-protective potential of the vaccine against two other recent clade 2 isolates (A/turkey/Turkey/1/2005 and A/Anhui/1/2005 which are, as defined by WHO, representatives of subclades 2.2 and 2.3 respectively). Methods and Findings Two doses of the recombinant A/Vietnam/1194/2004 (H5N1, clade 1) vaccine were administered 21 days apart to volunteers aged 18–60 years. We studied the cross-clade immunogenicity of the lowest antigen dose (3.8 µg haemagglutinin) given with (N = 20) or without adjuvant (N = 20). Immune responses were assessed at 21 days following the first and second vaccine doses and at 6 months following first vaccination. Vaccination with two doses of 3.8 µg of the adjuvanted vaccine induced four-fold neutralising seroconversion rates in 85% of subjects against A/turkey/Turkey/1/2005 (subclade 2.2) and 75% of subjects against A/Anhui/1/2005 (subclade 2.3) recombinant strains. There was no response induced against these strains in the non-adjuvanted group. At 6 months following vaccination, 70% and 60% of subjects retained neutralising antibodies against the recombinant subclade 2.2 and 2.3 strains, respectively and 40% of subjects retained antibodies against the recombinant subclade 2.1 A/Indonesia/5/2005 strain. Conclusions In addition to antigen dose-sparing, adjuvantation of inactivated split H5N1 vaccine promotes broad and persistent cross-clade immunity which is a pre-requisite for a pre-pandemic vaccine. Trial Registration ClinicalTrials.gov NCT00309634


PLOS ONE | 2008

Cross-Protection against Lethal H5N1 Challenge in Ferrets with an Adjuvanted Pandemic Influenza Vaccine

Benoît Baras; Koert J. Stittelaar; James H. Simon; Robert J.M.M. Thoolen; Sally P. Mossman; Frank Pistoor; Geert van Amerongen; Martine Wettendorff; Emmanuel Hanon; Albert D. M. E. Osterhaus

Background Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after the start of a pandemic outbreak. In the present study, we evaluated a split H5N1 A/H5N1/Vietnam/1194/04, clade 1 candidate vaccine, adjuvanted with a proprietary oil-in- water emulsion based Adjuvant System proven to be well-tolerated and highly immunogenic in the human (Leroux-Roels et al. (2007) The Lancet 370:580–589), for its ability to induce intra-subtypic cross-protection against clade 2 H5N1/A/Indonesia/5/05 challenge in ferrets. Methodology and Principal Findings All ferrets in control groups receiving non-adjuvanted vaccine or adjuvant alone failed to develop specific or cross-reactive neutralizing antibodies and all died or had to be euthanized within four days of virus challenge. Two doses of adjuvanted split H5N1 vaccine containing ≥1.7 µg HA induced neutralizing antibodies in the majority of ferrets to both clade 1 (17/23 (74%) responders) and clade 2 viruses (14/23 (61%) responders), and 96% (22/23) of vaccinees survived the lethal challenge. Furthermore lung virus loads and viral shedding in the upper respiratory tract were reduced in vaccinated animals relative to controls suggesting that vaccination might also confer a reduced risk of viral transmission. Conclusion These protection data in a stringent challenge model in association with an excellent clinical profile highlight the potential of this adjuvanted H5N1 candidate vaccine as an effective tool in pandemic preparedness.


Vaccine | 2010

Priming with AS03A-adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: An open non-randomised extension of a double-blind randomised primary study

Isabel Leroux-Roels; François Roman; Sheron Forgus; Cathy Maes; Fien De Boever; Mamadou Dramé; Paul Gillard; Robbert G. van der Most; Marcelle Van Mechelen; Emmanuel Hanon; Geert Leroux-Roels

An influenza vaccine with cross-immunogenic potential could play a key role in pandemic mitigation by promoting a rapid immune response to infection and/or subsequent vaccination with strains drifted from the primary vaccine strain. Here we assess the role of AS03(A) (an oil-in-water emulsion based Adjuvant System containing tocopherol) in this prime-boost concept using H5N1 as a model shift influenza antigen. In this open, non-randomised study (NCT00506350; an extension of an earlier randomised study) we assessed immunogenicity in nine groups of 35-50 volunteers aged 19-61 years following administration of AS03(A)-adjuvanted split-virion H5N1 vaccine containing 3.75mug of haemagglutinin (HA) from the A/Indonesia/5/2005(IBCDC-RG2) clade 2.1 strain. A single booster dose of vaccine was administered to four groups primed 14 months previously with different HA levels of AS03(A)-adjuvanted clade 1 A/Vietnam/1194/2004 H5N1 vaccine. Two booster doses (given 21 days apart) were administered to four groups primed 14 months previously with different HA levels of non-adjuvanted A/Vietnam/1194/2004 H5N1 vaccine and also to a control group of un-primed subjects. In individuals primed 14 months earlier with AS03(A)-adjuvanted A/Vietnam/1194/2004 vaccines, a single booster dose of AS03(A)-adjuvanted A/Indonesia/5/2005 induced rapid immune responses (licensure criteria met in 7-14 days) comparable to that observed in the un-primed control group following two doses of adjuvanted vaccine. In contrast, individuals primed with non-adjuvanted formulations exhibited minimal immune responses which, even after two doses, were unexpectedly much lower than that observed in un-primed subjects. AS03(A) enhances the initial priming effect of pandemic influenza vaccination enabling a rapid humoral response to single dose boosting with a heterologous strain at 14 months. In contrast, priming without adjuvant appears to inhibit the response to subsequent vaccination with a heterologous strain. These findings should guide the development of vaccines to combat the present influenza A/H1N1 pandemic.


Clinical Infectious Diseases | 2010

AS03A-Adjuvanted Influenza A (H1N1) 2009 Vaccine for Adults up to 85 Years of Age

François Roman; Tejaswini Vaman; Froukje Kafeja; Emmanuel Hanon; Pierre Van Damme

BACKGROUND Vaccination of high-risk groups was started shortly after the emergence of the influenza A (H1N1)2009 pandemic virus. METHODS Healthy adults were enrolled into 2 age strata: 18-60 years and 160 years, and received monovalent influenza vaccine containing 3.75 microg of A/California/2009 (H1N1) hemagglutinin antigen, adjuvanted with AS03A. Hemagglutination inhibition assay-based antibody titers against H1N1 vaccine were assessed after 1 vaccine dose(primary endpoint), after which subjects were randomized 1:1 to receive no further vaccination or a second dose.Immunogenicity endpoints were European licensure criteria for influenza vaccines. Exploratory analyses assessed the effect of previous seasonal influenza vaccination on responses to the H1N1 vaccine. RESULTS Licensure criteria for immunogenicity were fulfilled after 1 dose of H1N1 vaccine (N=240). For subjects 18-60 years of age, previous vaccination against seasonal influenza within the preceding 2 seasons resulted in significantly lower geometric mean titers (adjusted for baseline antibody titer) after 1 or 2 doses of H1N1 vaccine (P <.001 and P=.003, respectively). Transient mild or moderate injection-site pain was reported by 87.5%and 65.0% of subjects 18-60 years of age and >60 years of age, respectively, after the first dose, and in 63% of subjects overall after the second dose. CONCLUSIONS A single dose of 3.75 microg hemagglutinin antigen, AS03A-adjuvanted H1N1 2009 vaccine was immunogenic and well tolerated in adults. In exploratory analyses (of subjects 18-60 years of age), postvaccination antibody titers were lower in subjects who had previously received seasonal influenza vaccination, compared with those who had not. This phenomenon warrants further investigation. CLINICAL TRIALS REGISTRATION NCT00968526.


The Journal of Infectious Diseases | 2004

Human Cell Lymphotropic Virus (HTLV) Type-l-Specific CD8+ Cells: Frequency and Immunodominance Hierarchy

Alix Biancardi; Noam Fast; Tadahiko Igakura; Emmanuel Hanon; Angelina J. Mosley; Becca Asquith; Keith G. Gould; Sara E. Marshall; Graham P. Taylor; Charles R. M. Bangham

Human T cell lymphotropic virus type 1 (HTLV-1) causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We used interferon- gamma enzyme-linked immunospot assays with overlapping peptides spanning the entire HTLV-1 proteome to test whether the HTLV-1-specific CD8(+) T cells differed significantly in frequency or immunodominance hierarchy between patients with HAM/TSP and asymptomatic carriers and whether the frequency correlated with provirus load. Tax was the immunodominant target antigen. There was no significant qualitative or quantitative difference in the HTLV-1-specific CD8(+) T cell response between the 2 groups. Virus-specific CD8(+) T cell frequency alone does not indicate the effectiveness of the cytotoxic T lymphocyte response in controlling provirus load at equilibrium.


Journal of Immunology | 2004

Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4+ T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I

Tadahiko Igakura; Emmanuel Hanon; Angelina J. Mosley; Anna Barfield; Amanda L. Barnard; Lambrini Kaftantzi; Yuetsu Tanaka; Graham P. Taylor; Jonathan Weber; Charles R. M. Bangham

CD4+ T cells predominate in early lesions in the CNS in the inflammatory disease human lymphotropic T cell virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but the pathogenesis of the disease remains unclear and the HTLV-I-specific CD4+ T cell response has been little studied. We quantified the IFN-γ-producing HTLV-I-specific CD4+ T cells, in patients with HAM/TSP and in asymptomatic carriers with high proviral load, to test two hypotheses: that HAM/TSP patients and asymptomatic HTLV-I carriers with a similar proviral load differ in the immunodominance hierarchy or the total frequency of specific CD4+ T cells, and that HTLV-I-specific CD4+ T cells are preferentially infected with HTLV-I. The strongest CD4+ T cell response in both HAM/TSP patients and asymptomatic carriers was specific to Env. This contrasts with the immunodominance of Tax in the HTLV-I-specific CD8+ T cell response. The median frequency of HTLV-I-specific IFN-γ+ CD4+ T cells was 25-fold greater in patients with HAM/TSP (p = 0.0023, Mann-Whitney) than in asymptomatic HTLV-I carriers with a similar proviral load. Furthermore, the frequency of CD4+ T cells infected with HTLV-I (expressing Tax protein) was significantly greater (p = 0.0152, Mann-Whitney) among HTLV-I-specific cells than CMV-specific cells. These data were confirmed by quantitative PCR for HTLV-I DNA. We conclude that the high frequency of specific CD4+ T cells was associated with the disease HAM/TSP, and did not simply reflect the higher proviral load that is usually found in HAM/TSP patients. Finally, we conclude that HTLV-I-specific CD4+ T cells are preferentially infected with HTLV-I.


Journal of Virology | 2003

High Circulating Frequencies of Tumor Necrosis Factor Alpha- and Interleukin-2-Secreting Human T-Lymphotropic Virus Type 1 (HTLV-1)-Specific CD4+ T Cells in Patients with HTLV-1-Associated Neurological Disease

Tadahiko Igakura; Emmanuel Hanon; Angelina J. Mosley; Becca Asquith; Keith G. Gould; Graham P. Taylor; Jonathan Weber; Charles R. M. Bangham

ABSTRACT Significantly higher frequencies of tumor necrosis factor alpha- and interleukin-2-secreting human T-lymphotropic virus type 1 (HTLV-1)-specific CD4+ T cells were present in the peripheral blood mononuclear cells of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients than in those of asymptomatic carriers with similar provirus loads. The data suggest that HTLV-1-specific CD4+ T cells play a role in the pathogenesis of HAM/TSP.


Clinical and Vaccine Immunology | 2011

Effect on Cellular and Humoral Immune Responses of the AS03 Adjuvant System in an A/H1N1/2009 Influenza Virus Vaccine Administered to Adults during Two Randomized Controlled Trials

François Roman; Frédéric Clement; Walthère Dewé; Karl Walravens; Cathy Maes; Julie Willekens; Fien De Boever; Emmanuel Hanon; Geert Leroux-Roels

ABSTRACT The influence of AS03A, a tocopherol oil-in-water emulsion-based adjuvant system, on humoral and cell-mediated responses to A/California/7/2009 H1N1 pandemic vaccine was investigated. In two observer-blind studies, a total of 261 healthy adults aged 18 to 60 years were randomized to receive either AS03A-adjuvanted H1N1 vaccine containing 3.75 μg hemagglutinin (HA) or nonadjuvanted H1N1 vaccine containing 15 or 3.75 μg HA on days 0 and 21. Hemagglutination inhibition (HI) antibody and T-cell responses were analyzed up to day 42. A first dose of AS03A-adjuvanted vaccine (3.75 μg HA) or nonadjuvanted vaccine (15 μg HA) induced HI responses of similar magnitudes that exceeded licensure criteria (e.g., 94 to 100% with titers of ≥40). A lower response following 3.75 μg HA without adjuvant was observed (73% with titers of ≥40). Following a second dose, geometric mean HI titers at day 42 were higher for AS03A-adjuvanted vaccine (636 and 637) relative to nonadjuvanted vaccine (341 for 15 μg HA and 150 for 3.75 μg HA). Over the 42-day period, the increase in frequency of A/H1N1/2009-specific CD4+ T cells was significantly higher in the adjuvanted group than in the nonadjuvanted group. There was no evidence of correlation between baseline CD4+ T-cell frequencies and day 21 HI antibody titers, while there was some correlation (R = 0.35) between day 21 CD4+ T-cell frequencies and day 42 HI titers. AS03A adjuvant enhanced the humoral and CD4+ T-cell-mediated responses to A/H1N1/2009 vaccine. Baseline A/H1N1/2009-specific CD4+ T-cell frequencies did not predict post-dose 1 antibody responses, but there was some correlation between post-dose 1 CD4+ T-cell frequencies and post-dose 2 antibody responses.


Influenza and Other Respiratory Viruses | 2008

A vaccine manufacturer’s approach to address medical needs related to seasonal and pandemic influenza viruses

Benoît Baras; Nancy Bouveret; Jeanne-Marie Devaster; Louis Fries; Paul Gillard; Roland Sänger; Emmanuel Hanon

Abstract Vaccination is considered to be one of the most effective tools to decrease morbidity as well as mortality caused by influenza viruses.

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Yuetsu Tanaka

University of the Ryukyus

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