Publications
198 results found
Sullivan AK, Hardy GAD, Nelson MR, et al., 2003, Interleukin-2-associated viral breakthroughs induce HIV-1-specific CD4 T cell responses in patients on fully suppressive highly active antiretroviral therapy, AIDS, Vol: 17, Pages: 628-629, ISSN: 0269-9370
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- Citations: 10
Pido-Lopez J, Burton C, Hardy G, et al., 2003, Thymic output during initial highly active antiretroviral therapy (HAART) and during HAART supplementation with interleukin 2 and/or with HIV type 1 immunogen (Remune), AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 19, Pages: 103-109, ISSN: 0889-2229
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- Citations: 18
Stebbing J, Patterson S, Gotch F, 2003, New insights into the immunology and evolution of HIV, CELL RESEARCH, Vol: 13, Pages: 1-7, ISSN: 1001-0602
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- Citations: 18
Prakash M, Patterson S, Gotch F, et al., 2003, Recruitment of CD4<SUP>+</SUP> T lymphocytes and macrophages into the cervical epithelium of women after coitus, AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Vol: 188, Pages: 376-381, ISSN: 0002-9378
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- Citations: 32
Gill J, Bourboulia D, Wilkinson J, et al., 2002, Prospective study of the effects of antiretroviral therapy on Kaposi sarcoma-associated herpesvirus infection in patients with and without Kaposi sarcoma, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 31, Pages: 384-390, ISSN: 1525-4135
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- Citations: 99
Burton CT, Hardy GAD, Sullivan AK, et al., 2002, Impact of NNRTI compared to PI-based highly active antiretroviral therapy on CCR5 receptor expression, <i>β</i>-chemokines and IL-16 secretion in HIV-1 infection, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 130, Pages: 286-292, ISSN: 0009-9104
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- Citations: 11
Imami N, Pires A, Hardy G, et al., 2002, A balanced type 1/type 2 response is associated with long-term nonprogressive human immunodeficiency virus type 1 infection, Journal of Virology, Vol: 76, Pages: 9011-9023, ISSN: 0022-538X
Previous reports have emphasized the requirements for strong type 1 cell-mediated responses in the control of human immunodeficiency virus type 1 (HIV-1). HIV-1 Gag p24-specific CD4 helper T-lymphocyte (HTL) responses have been shown to inversely correlate with viral burden in HIV-1-infected individuals. In this study, peripheral blood mononuclear cells from 70 individuals with chronic progressive HIV-1 infection (clinical progressors), 10 clinical nonprogressors, and 3 immunologically discordant progressors were assessed for HTL proliferation and type 1/type 2 cytokine production. Clinical progressors lacked functional HIV-1-specific HTLs with proliferative and cytokine-producing capacity. Clinical nonprogressors were found to respond to a wide range of HIV-1 antigens from different clades, producing both type 1 and type 2 cytokines. Immunologically discordant progressors responded strongly to clade B Gag p24 with a type 1 cytokine profile but not to other antigens. Thus, in contrast to clinical nonprogressors, neither progressors nor immunologically discordant progressors secreted interleukin-4 (IL-4) in response to HIV-1 antigens. Both clinical nonprogressors and immunologically discordant progressors responded broadly to B clade Gag p24-overlapping peptides. However, IL-4 production in the nonprogressors was restricted to a limited number of p24 peptides. No HIV-1-specific T-cell responses were seen in 20 seronegative controls. Additionally, we observed a rapid type 1 to type 2 shift in the response of one immunologically discordant progressor upon onset of clinical symptoms. These results suggest that a balanced type 1/type 2 profile correlates with successful long-term control of HIV-1.
Imami N, Hardy G, Pires A, et al., 2002, Immune reconstitution in HIV-1-infected patients., Curr Opin Investig Drugs, Vol: 3, Pages: 1138-1145, ISSN: 1472-4472
HIV-1-specific CD8 cytotoxic and CD4 helper T-lymphocytes, which are respectively the central effector and regulatory cells in viral infections, together with fully functional antigen-presenting cells, are essential at all stages of HIV-1 infection to control viral activity. Recent studies indicate that such protective HIV-1-specific immune responses can be preserved/induced in HIV-1-infected individuals, utilizing strategies such as treatment interruption after early HAART. Despite successful combination antiretroviral drug therapy, strong anti-HIV-1 T-cell responses are often not apparent in chronic HIV-1 infection, diminishing the probability of viral eradication. Thus, the therapeutic use of immunization and cytokines are required to induce and steer immunity towards a desirable outcome. Here, we review and discuss therapeutic immunization and immunotherapy with regard to their potential use in the treatment of chronic HIV-1 infection.
Hardy GA, Imami N, Gotch FM, 2002, Improving HIV-specific immune responses in HIV-infected patients., J HIV Ther, Vol: 7, Pages: 40-45, ISSN: 1462-0308
Deficiencies in potentially highly protective HIV-1-specific immune responses have led to interventions with immunotherapeutic strategies such as post-exposure vaccination. The application of exogenous antigen to the HIV-infected individual by therapeutic vaccination might be expected to induce renewed virus-specific effector T-cell and neutralising-antibody responses. However, the nature of HIV-1 immunopathogenicity precludes this approach: high levels of viral turnover, persistent expression and presentation of HIV-1 antigen to the immune system, T-cell hyperactivation and exhaustion and clonal T-cell anergy all successfully counter any effect of exogenous antigen. Even with the use of highly active antiretroviral therapy (HAART), when HIV-1 activity is profoundly restricted, the induction of immune responses remains problematic. Different vaccine strategies are currently being tested, including a whole killed virus preparation (Remune), a yeast virus-like particle (p24 VLP), whole antigen preparations (VaxSyn), canarypox immunogens (ALVAC) and DNA plasmids. Therapeutic vaccine strategies currently in the earliest stages of development include adenovirus vectors and a topical DNA preparation, DermaVir.
Imami N, Gotch F, 2002, Mechanisms of loss of HIV-1-specific T-cell responses., J HIV Ther, Vol: 7, Pages: 30-34, ISSN: 1462-0308
Virus-specific T-cell responses, important for the control of HIV-1 infection, are seen in HIV-1-infected subjects in the early stages of infection. A progressive variable decline in HIV-1-specific CD4 and CD8 T-cell responses during the course of the infection is not reversed by the administration of potent antiretroviral drugs. The mechanisms responsible for this HIV-1-inflicted loss are complex, involving processes ranging from T-cell ontogeny to the final stages of antigen presentation and T-cell differentiation. HIV-1-specific CD4 and CD8 T cells are present in most patients, but have been rendered anergic, either directly by HIV-1 or indirectly by clonal inactivation, exhaustion and/or suppression. The absence of functional HIV-1-specific T cells in chronic infection, even after the initiation of antiretroviral therapy, indicates that additional immunomodulatory therapy is required. To induce or maintain such cellular responses in an immunosuppressed environment of chronic infection is proving difficult to achieve. The induction of virus-specific CD4 T-cell and, subsequently, CD8 T-cell responses may require different novel approaches based on an appreciation of the complex mechanisms involved in the loss of these responses.
Miao YM, Hayes PJ, Gotch FM, et al., 2002, Elevated mucosal addressin cell adhesion molecule-1 expression in acquired immunodeficiency syndrome is maintained during antiretroviral therapy by intestinal pathogens and coincides with increased duodenal CD4 T cell densities, JOURNAL OF INFECTIOUS DISEASES, Vol: 185, Pages: 1043-1050, ISSN: 0022-1899
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- Citations: 18
Wilkinson J, Cope A, Gill J, et al., 2002, Identification of Kaposi's sarcoma-associated herpesvirus (KSHV)-specific cytotoxic T-lymphocyte epitopes and evaluation of reconstitution of KSHV-specific responses in human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy, Journal of Virology, Vol: 76, Pages: 2634-2640, ISSN: 0022-538X
Following the introduction of highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) has significantly declined in human immunodeficiency virus type 1 (HIV-1)-positive (HIV-1+) individuals and clinical remission is often observed. We hypothesize that these effects are partly due to anti-KS-associated herpesvirus (KSHV) immune restoration. Here, 15-mer overlapping peptides from proteins K12 and K8.1 were used to identify novel KSHV-specific cytotoxic T-lymphocyte epitopes. Three immunogenic peptides, two lytic and one latent, were subsequently used to monitor the anti-KSHV CD8+ T-cell responses in a cohort of 19 HIV-1+ KSHV+/− KS+/− individuals during 52 weeks of HAART. KSHV and HIV-1 loads, KSHV antibody titers, and both CD4+ and CD8+ T-lymphocyte counts were enumerated. Prior to HAART, the total number of spot-forming cells (SFC) for all three peptides correlated with both CD4+ and CD8+ T-lymphocyte counts (P ≤ 0.05) in the KSHV-positive KS-positive cohort (n = 11). Following 52 weeks of HAART, significant decreases in HIV-1 and KSHV loads were associated with significant increases in CD4+ T-lymphocyte counts and number of SFC for the three KSHV-specific peptides. Although these increases were modest in comparison to the number of SFC observed with the HIV-1 gag peptide SLYNTVATL, they represented a fourfold increase from the baseline, continuing an upward trend to week 52.
Imami N, Gotch F, 2002, Prospects for immune reconstitution in HIV-1 infection, Clinical and Experimental Immunology, Vol: 127, Pages: 402-411, ISSN: 0009-9104
Prakash M, Kapembwa MS, Gotch F, et al., 2002, Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4<SUP>+</SUP> T cells in the cervical epithelium of healthy women, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Vol: 54, Pages: 117-131, ISSN: 0165-0378
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- Citations: 62
Tchilian EZ, Dawes R, Ramaley PA, et al., 2002, A CD45 polymorphism associated with abnormal splicing is absent in African populations, IMMUNOGENETICS, Vol: 53, Pages: 980-983, ISSN: 0093-7711
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- Citations: 21
Pido-Lopez J, Pires A, Nelson M, et al., 2002, Thymic activity in late-stage HIV-1 infected individuals receiving highly active antiretroviral therapy: potential effect of steroid therapy, HIV Medicine, Vol: 3, Pages: 56-61, ISSN: 1464-2662
OBJECTIVE: Our objective was to monitor the effect of steroid therapy on the thymic output and function of late-stage HIV-1-infected patients undergoing highly active antiretroviral therapy (HAART). DESIGN: The indirect measurement of T cells that have recently emigrated from the thymus as a means of quantifying thymic output, and therefore thymic function, was achieved through use of the polymerase chain reaction-based signal joint T cell receptor rearrangement excision circles (sjTREC) assay. Proliferative capacity and interleukin (IL)-2 and IL-4 production by T cells after antigenic, mitogenic and IL-2 stimulation were also analysed. METHOD: Measurements were made of sjTREC levels in peripheral blood mononuclear cell DNA samples from five HIV-1 infected patients (one on steroid therapy prior to and at the time of sample extraction) receiving HAART. IL-2 and IL-4 production and proliferative capacity were also measured in three patients, including the patient receiving steroids. RESULT: The sjTREC assay gave an extremely weak result for the patient on steroids but, under the same assay conditions, provided clear, positive readings for the four patients not on steroids. Comparison of the patients' cytokine profiles revealed that IL-2 production was generally low or absent in all three patients tested but that IL-4 production was significantly higher in the patient given steroids. Functional potential as revealed by proliferation assays showed very low or absent cellular proliferation. CONCLUSION: The thymic contribution to the restoration of T lymphocyte numbers, particularly during the treatment of HIV-1 infection, may become compromised if thymic inhibitory factors such as steroids are used. Furthermore, the use of steroids may also favour the development of a T helper 2 response, which could prove particularly undesirable during HIV-1 infection.
Gotch F, Hardy G, Imami N, et al., 2002, The effects of immunotherapy with cytokines and/or vaccines in HAART treated patients, 14th International AIDS Conference, Publisher: MEDIMOND S R L, Pages: 279-284
Tchilian EZ, Wallace DL, Dawes R, et al., 2001, A point mutation in CD45 may be associated with an increased risk of HIV-1 infection (vol 15, pg 1892, 2001), AIDS, Vol: 15, Pages: 2210-2210, ISSN: 0269-9370
Gotch F, Heeney J, Manca F, 2001, Special issue: The third international summit meeting on: "Immunological correlates of protection from HIV infection and disease", Sestri Levante, Italy, 30 November-3 December 2000., IMMUNOLOGY LETTERS, Vol: 79, Pages: 1-2, ISSN: 0165-2478
Gotch F, 2001, Dedicated to the memory of Janis V. Giorgi (1947-2000), IMMUNOLOGY LETTERS, Vol: 79, Pages: VII-VII, ISSN: 0165-2478
Imami N, Hardy G, Burton C, et al., 2001, Immune responses and reconstitution in HIV-1 infected individuals: impact of anti-retroviral therapy, cytokines and therapeutic vaccination, IMMUNOLOGY LETTERS, Vol: 79, Pages: 63-76, ISSN: 0165-2478
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- Citations: 25
Imami N, Sullivan AK, Gotch FM, 2001, Immunomodulation in HIV-1 infection in the HAART era., J HIV Ther, Vol: 6, Pages: 77-84, ISSN: 1462-0308
Prakash M, Kapembwa MS, Gotch F, et al., 2001, Higher levels of activation markers and chemokine receptors on T lymphocytes in the cervix than peripheral blood of normal healthy women, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Vol: 52, Pages: 101-111, ISSN: 0165-0378
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- Citations: 21
Gotch FM, Imami N, Hardy G, 2001, Candidate vaccines for immunotherapy in HIV., HIV Med, Vol: 2, Pages: 260-265, ISSN: 1464-2662
In this short article we review the immunopathology of HIV infection and delineate the kinds of immune responses seen in acute infection and in long-term nonprogression that are understood to be necessary if the host is to maintain long-term control of the virus. In this context we discuss the potential promise of therapeutic vaccination in HIV infection.
Gotch F, 2001, AIDS vaccine 2001., IDrugs, Vol: 4, Pages: 1141-1143, ISSN: 1369-7056
It has been reported that 5.4 million new HIV infections occur each year, 10% of which are in children and 50% in females. Over 90% of infections occur in the developing world where highly active antiretroviral therapy is unlikely to be readily available. Therefore, the need for a prophylactic vaccine for HIV is compelling. All sessions of 'AIDS Vaccine 2001' were valuable, but this report mainly considers two slide sessions where new candidate vaccines and vaccine strategies were discussed. It is of major importance that as many novel vaccine strategies as possible are explored, and that meaningful comparisons are made between the responses they induce. Even a vaccine that does not offer full sterilizing immunity to HIV infection could have a dramatic effect on the pathogenesis of HIV disease and on transmission of HIV from person to person.
Tchilian EZ, Wallace DL, Dawes R, et al., 2001, A point mutation in CD45 may be associated with an increased risk of HIV-1 infection, AIDS, Vol: 15, Pages: 1892-1894
King DJS, Gotch FM, Larsson-Sciard EL, 2001, T-cell re-population in HIV-infected children on highly active anti-retroviral therapy (HAART), CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 125, Pages: 447-454, ISSN: 0009-9104
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- Citations: 14
Imami N, Hardy G, Gotch F, 2001, Development of immunotherapeutic strategies for HIV-1, EXPERT OPINION ON BIOLOGICAL THERAPY, Vol: 1, Pages: 803-816, ISSN: 1471-2598
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- Citations: 11
Imami N, Hardy G, Pires A, et al., 2001, Detection and quantification of HIV-1 specific CD4 helper and CD8 cytotoxic cells: their role in HIV-1-infected individuals and vaccine recipients., HIV Med, Vol: 2, Pages: 146-153, ISSN: 1464-2662
There is a strong link between virus specific CD8 T-cell function and the efficiency of regulatory CD4 helper T cells. Controlling viraemia in HIV-1-infected individuals requires the maintenance of strong CD4 and CD8 T-cell responses. These responses should be elicited by prophylactic vaccination and by postexposure immunotherapy. This review will examine the methods that are available for the detection and quantification of HIV-1 specific CD4 and CD8 T-cell responses. We will also discuss the methods that should be used to identify these responses in HIV-1-infected individuals, seropositive recipients of immunotherapy and seronegative vaccinees. Finally, we will give examples of how responses observed in vitro relate to those known to occur in vivo.
Dat NV, 2001, Outcomes of a trial of HIV-1 immunogen in patients with HIV infection, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol: 285, Pages: 2191-2191, ISSN: 0098-7484
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- Citations: 1
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