Publications
198 results found
Meys R, Purdie KJ, de Koning MNC, et al., 2016, HLA Immunogenotype Determines Persistent Human Papillomavirus Virus Infection in HIV-Infected Patients Receiving Antiretroviral Treatment, JOURNAL OF INFECTIOUS DISEASES, Vol: 213, Pages: 1717-1724, ISSN: 0022-1899
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- Citations: 5
Goolamali SI, Meys R, Shim T, et al., 2015, Immunogenetics of non-melanoma skin cancer/pre-cancer in HIV, 45th Annual Meeting of the European-Society-for-Dermatological-Research, Publisher: NATURE PUBLISHING GROUP, Pages: S34-S34, ISSN: 0022-202X
Munseri PJ, Kroidl A, Nilsson C, et al., 2015, Priming with a Simplified Intradermal HIV-1 DNA Vaccine Regimen followed by Boosting with Recombinant HIV-1 MVA Vaccine Is Safe and Immunogenic: A Phase IIa Randomized Clinical Trial, PLOS ONE, Vol: 10, ISSN: 1932-6203
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- Citations: 34
Serwanga J, Nakiboneka R, Mugaba S, et al., 2015, Frequencies of Gag-restricted T-cell escape "footprints" differ across HIV-1 clades A1 and D chronically infected Ugandans irrespective of host HLA B alleles, VACCINE, Vol: 33, Pages: 1664-1672, ISSN: 0264-410X
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- Citations: 6
Herasimtschuk A, Downey J, Nelson M, et al., 2014, Therapeutic immunisation plus cytokine and hormone therapy improves CD4 T-cell counts, restores anti-HIV-1 responses and reduces immune activation in treated chronic HIV-1 infection, VACCINE, Vol: 32, Pages: 7005-7013, ISSN: 0264-410X
BackgroundThis randomised, open label, phase I, immunotherapeutic study investigated the effects of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), recombinant human growth hormone (rhGH), and therapeutic immunisation (a Clade B DNA vaccine) on combination antiretroviral therapy (cART)-treated HIV-1-infected individuals, with the objective to reverse residual T-cell dysfunction.MethodsTwelve HIV-1+ patients on suppressive cART with baseline CD4 T-cell counts >400 cells/mm3 blood were randomised into one of three groups: (1) vaccine, IL-2, GM-CSF and rhGH (n = 3); (2) vaccine alone (n = 4); or (3) IL-2, GM-CSF and rhGH (n = 5). Samples were collected at weeks 0, 1, 2, 4, 6, 8, 12, 16, 24 and 48. Interferon (IFN)-γ, IL-2, IL-4 and perforin ELISpot assays performed at each time point quantified functional responses to Gag p17/p24, Nef, Rev, and Tat peptides; and detailed T-cell immunophenotyping was undertaken by flow cytometry. Proviral DNA was also measured.ResultsMedian baseline CD4 T-cell count was 757 cells/mm3 (interquartile range [IQR] 567–886 cells/mm3), median age 48 years (IQR 42–51 years), and plasma HIV-1-RNA <50 copies/ml for all subjects. Patients who received vaccine plus IL-2, GM-CSF and rhGH (group 1) showed the most marked changes. Assessing mean changes from baseline to week 48 revealed significantly elevated numbers of CD4 T cells (p = 0.0083) and improved CD4/CD8 T-cell ratios (p = 0.0033). This was accompanied by a significant reduction in expression of CD38 on CD4 T cells (p = 0.0194), significantly increased IFN-γ and IL-2 production in response to Gag (p = 0.0122) and elevated IFN-γ production in response to Tat (p = 0.041) at week 48 compared to baseline. Subjects in all treatment groups showed significantly reduced PD-1 expression at week 48 compared to baseline, with some reductions in proviral DNA.ConclusionsMultifarious immunotherapeutic approaches in the context of fully s
Page EE, Greathead L, Metcalf R, et al., 2014, Loss of Th22 Cells Is Associated With Increased Immune Activation and IDO-1 Activity in HIV-1 Infection, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 67, Pages: 227-235, ISSN: 1525-4135
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- Citations: 32
Shim TN, Meys R, Goolamali SI, et al., 2014, Human leucocyte antigen and human papillomavirus in male genital lichen sclerosus, penile precancer and penile cancer, 15th World Congress on Cancers of the Skin, Publisher: WILEY-BLACKWELL, Pages: 31-31, ISSN: 0007-0963
Greathead L, Metcalf R, Gazzard B, et al., 2014, CD8(+)/CD161(++) mucosal-associated invariant T-cell levels in the colon are restored on long-term antiretroviral therapy and correlate with CD8(+) T-cell immune activation, AIDS, Vol: 28, Pages: 1690-1692, ISSN: 0269-9370
Mucosal-associated invariant T (MAIT) cells are tissue-homing T cells recently implicated in HIV pathogenesis. We found that the proportion of MAIT cell in blood and colon of HIV+ patients are reduced in untreated infection. Antiretroviral therapy restored colonic but not blood MAIT cell percentages. We observed a negative correlation between colonic MAIT cells and T-cell activation in blood and suggest mucosal MAIT cell depletion may contribute to systemic immune activation in HIV infection.
Page E, Greathead L, Hart M, et al., 2013, Alterations in the balance of Th1 (CXCR3+CCR5+) cells to Th17 (CCR4+CCR6+CCR10-) and Th22 (CCR4+CCR6+CCR10+) cells in HIV-1/HCV coinfection is associated with immune activation, microbial translocation and liver fibrosis, HIV MEDICINE, Vol: 14, Pages: 3-3, ISSN: 1464-2662
Herasimtschuk A, Downey J, Nelson M, et al., 2013, Therapeutic immunisation in conjunction with IL-2, GM-CSF and rhGH improves CD4 T-cell counts and reduces immune activation in cART-treated HIV-1-positive patients: a Phase I clinical study, HIV MEDICINE, Vol: 14, Pages: 10-10, ISSN: 1464-2662
Mletzko S, Rai A, Westrop S, et al., 2013, The role of interleukin-6 and interleukin-6 receptor in multicentric Castleman's disease (MCD): frequency of polymorphism, HIV MEDICINE, Vol: 14, Pages: 26-26, ISSN: 1464-2662
Benlahrech A, Yasmin A, Westrop S, et al., 2013, Antiretroviral therapy restores HIV-1-induced abnormal expression of immunoregulatory molecules by plasmacytoid DC, HIV MEDICINE, Vol: 14, Pages: 25-25, ISSN: 1464-2662
Benlahrech A, Yasmin A, Westrop SJ, et al., 2012, Dysregulated immunophenotypic attributes of plasmacytoid but not myeloid dendritic cells in HIV-1 infected individuals in the absence of highly active anti-retroviral therapy, Clinical and Experimental Immunology, Vol: 170, Pages: 212-221, ISSN: 0009-9104
Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1+ patients. DC from healthy controls, untreated HIV-1+ and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1+ patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1+ patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.
Munseri P, Kroidl A, Nilsson C, et al., 2012, Priming with a "simplified regimen" of HIV-1 DNA vaccine is as good as a "standard regimen" when boosted with heterologous HIV-1 MVA vaccine, RETROVIROLOGY, Vol: 9, ISSN: 1742-4690
Ruffin N, Borggren M, Euler Z, et al., 2012, Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 10, ISSN: 1479-5876
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- Citations: 6
Serwanga J, Mugaba S, Pimego E, et al., 2012, Profile of T Cell Recognition of HIV Type 1 Consensus Group M Gag and Nef Peptides in a Clade A1-and D-Infected Ugandan Population, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 28, Pages: 384-392, ISSN: 0889-2229
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- Citations: 8
Mletzko S, Shahrabi Y, Hislop A, et al., 2012, <i>Ex</i>-<i>vivo</i> recognition of immediate-early T cell epitopes within open reading frame ORF50 and K8 of Kaposi's sarcoma-associated herpesvirus (KSHV) by HIV/KSHV-coinfected individuals, Publisher: WILEY-BLACKWELL, Pages: 32-32, ISSN: 1464-2662
Herasimtschuk A, Thaventhiran T, Nelson M, et al., 2012, Distinct HIV-1 Gag-and Nef- specific responses correlate with immunophenotype in treated chronic HIV-1 infection, HIV MEDICINE, Vol: 13, Pages: 32-32, ISSN: 1464-2662
Guergnon J, Dalmasso C, Broet P, et al., 2012, Single-nucleotide polymorphism-defined Class I and Class III major histocompatibility complex genetic subregions contribute to natural long-term nonprogression in HIV infection, Journal of Infectious Diseases, Vol: 205, Pages: 718-724, ISSN: 0022-1899
We performed a genome-wide association study comparing a cohort of 144 human immunodeficiency virus (HIV type 1–infected, untreated white long-term nonprogressors (LTNPs) with a cohort of 605 HIV-1–infected white seroconverters. Forty-seven single-nucleotide polymorphisms (SNPs), located from class I to class III major histocompatibility complex (MHC) subregions, show statistical association (false discovery rate, <0.05) with the LTNP condition, among which 5 reached genome-wide significance after Bonferonni correction. The MHC LTNP–associated SNPs are ordered in ≥4 linkage disequilibrium blocks; interestingly, an MHC class III linkage disequilibrium block (defined by the rs9368699 SNP) seems specific to the LTNP phenotype.
Herasimtschuk A, Thaventhiran T, Nelson M, et al., 2012, Distinct HIV-1 Gag-and Nef- specific responses correlate with immunophenotype in treated chronic HIV-1 infection, 18th Annual Conference of the British HIV Association
Downey JS, Attaf M, Moyle G, et al., 2011, T-cell signalling in antiretroviral-treated, aviraemic HIV-1-positive individuals is present in a raised state of basal activation that contributes to T-cell hyporesponsiveness, AIDS, Vol: 25, Pages: 1981-1986, ISSN: 0269-9370
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- Citations: 3
Page EE, Clarke SA, Hart MS, et al., 2011, LIVER FIBROSIS IN HIV/HCV CO-INFECTION: THE ROLE OF TH17 AND TH22 CELLS, 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD), Publisher: WILEY-BLACKWELL, Pages: 1323A-1323A, ISSN: 0270-9139
Clark S, Page E, Ford T, et al., 2011, Reduced T<sub>H</sub>1/T<sub>H</sub>17 CD4 T-cell numbers are associated with impaired purified protein derivative-specific cytokine responses in patients with HIV-1 infection, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 128, Pages: 838-U547, ISSN: 0091-6749
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- Citations: 12
Edmonds E, Barton G, Buisson S, et al., 2011, Gene expression profiling in male genital lichen sclerosus, INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol: 92, Pages: 320-325, ISSN: 0959-9673
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- Citations: 32
Gudmundsdotter L, Wahren B, Haller BK, et al., 2011, Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial, VACCINE, Vol: 29, Pages: 5558-5566, ISSN: 0264-410X
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- Citations: 25
Robey RC, Mletzko S, Bower M, et al., 2011, <i>Ex</i>-<i>Vivo</i> Recognition of Late-Lytic CD8 Epitopes Specific for Kaposi's Sarcoma-Associated Herpesvirus (KSHV) by HIV/KSHV-Coinfected Individuals, VIRAL IMMUNOLOGY, Vol: 24, Pages: 211-220, ISSN: 0882-8245
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- Citations: 5
Matthews NC, Goodier MR, Robey RC, et al., 2011, Killing of Kaposi's sarcoma-associated herpesvirus-infected fibroblasts during latent infection by activated natural killer cells, European Journal of Immunology, Vol: 41, Pages: 1958-1968, ISSN: 1521-4141
Kaposi's sarcoma-associated herpesvirus (KSHV) establishes life-long infection by evading clearance by the host immune system. In de novo infection and lytic replication, KSHV escapes cytotoxic T cells and NK cells through downregulation of MHC class-I and ICAM-1 molecules and associated antigens involved in forming and sustaining the immunological synapse. However, the efficacy of such mechanisms in the context of the predominantly latent KSHV infection reported in Kaposi's sarcoma (KS) lesions is unclear. Using primary dermal fibroblasts in a novel in vitro model of chronic latent KSHV infection, we generated target cells with viral loads similar to those in spindle cells extracted from KS lesions. We show that latently KSHV-infected fibroblasts had normal levels of MHC-class I, ICAM-1, HLA-E and NKG2D ligand expression, were resistant to NK-cell natural cytotoxicity and were highly susceptible to killing by cytokine-activated immunocompetent NK cells. KSHV-infected fibroblasts expressed normal levels of IFN-γR1 and responded to exogenous IFN-γ by upregulating MHC class I, ICAM-1 and HLA-E and resisting activated NK-cell killing. These data demonstrate that physiologically relevant levels of latent KSHV infection in primary cells cause limited activation of resting NK cells and confer little specific resistance to control by activated NK cells.
Guimaraes-Walker A, Mackie N, McCormack S, et al., 2011, Lessons from IAVI-006, a Phase I clinical trial to evaluate the safety and immunogenicity of the pTHr.HIVA DNA and MVA.HIVA vaccines in a prime-boost strategy to induce HIV-1 specific T-cell responses in healthy volunteers (vol 26, pg 6671, 2008), VACCINE, Vol: 29, Pages: 3511-3511, ISSN: 0264-410X
Brinckmann S, da Costa K, van Gils MJ, et al., 2011, Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 9
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- Citations: 8
Mletzko S, Kyriakou A, Robey R, et al., 2011, Impaired dendritic cell (DC) function in Kaposi's sarcoma-associated herpesvirus (KSHV) infections, HIV MEDICINE, Vol: 12, Pages: 28-29, ISSN: 1464-2662
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