Imperial College London

ProfessorRobinShattock

Faculty of MedicineDepartment of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

270 results found

Harman SJ, Herrera C, Armanasco N, Nuttall J, Romano J, Shattock RJet al., 2010, L'644, a cholesterol derivatized version of the gp41 fusion peptide C34, provides superior activity in preclinical microbicide assays (oral presentation given by C Herrera), Microbicides 2010

Conference paper

Jespers V, Harandi AM, Hinkula J, Medaglini D, Le Grand R, Stahl-Hennig C, Bogers W, El Habib R, Wegmann F, Fraser C, Cranage M, Shattock RJ, Spetz A-Let al., 2010, Assessment of mucosal immunity to HIV-1, EXPERT REVIEW OF VACCINES, Vol: 9, Pages: 381-394, ISSN: 1476-0584

Journal article

Harandi AM, Medaglini D, Shattock RJ, 2010, Vaccine adjuvants: A priority for vaccine research, VACCINE, Vol: 28, Pages: 2363-2366, ISSN: 0264-410X

Journal article

Harman SJ, Herrera C, Armanasco N, Fletcher P, Nuttall J, Romano J, Shattock RJet al., 2010, L'644, a cholesterol derivatized version of the gp41 fusion peptide C34, provides superior activity in preclinical microbicide assays (oral presentation given by C Herrera), 17th Conference on Retroviruses and Opportunistic Infections

Conference paper

Cranage MP, Fraser CA, Stevens Z, Huting J, Chang M, Jeffs SA, Seaman MS, Cope A, Cole T, Shattock RJet al., 2010, Repeated vaginal administration of trimeric HIV-1 clade C gp140 induces serum and mucosal antibody responses, MUCOSAL IMMUNOLOGY, Vol: 3, Pages: 57-68, ISSN: 1933-0219

Journal article

Curran RM, Donnelly L, Morrow RJ, Fraser C, Andrews G, Cranage M, Malcolm RK, Shattock RJ, Woolfson ADet al., 2009, Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicits specific immune responses, VACCINE, Vol: 27, Pages: 6791-6798, ISSN: 0264-410X

Journal article

Richardson-Harman N, Lackman-Smith C, Fletcher PS, Anton PA, Bremer JW, Dezzutti CS, Elliott J, Grivel J-C, Guenthner P, Gupta P, Jones M, Lurain NS, Margolis LB, Mohan S, Ratner D, Reichelderfer P, Roberts P, Shattock RJ, Cummins JEet al., 2009, Multisite Comparison of Anti-Human Immunodeficiency Virus Microbicide Activity in Explant Assays Using a Novel Endpoint Analysis, JOURNAL OF CLINICAL MICROBIOLOGY, Vol: 47, Pages: 3530-3539, ISSN: 0095-1137

Journal article

Mann JF, Miranda de Stegmann DS, Klein K, Steih D, Cranage MP, Shattock RJ, McKay PFet al., 2009, Mucosal vaccination with a transferrin-gp140 conjugate via the nasal but not vaginal route elicits robust systemic and vaginal IgG and IgA responses, AIDS Vaccine 2009

Conference paper

Cranage M, Fraser C, Cope A, McKay PF, Elsley W, Page M, Mahmoud AN, DaCosta K, Fletcher P, Armanasco N, Almond N, Shattock RJet al., 2009, Intravaginal administration of HIV-1ZM96 gp140 augments systemic and mucosal antibody responses following systemic priming with adjuvanted protein., AIDS Vaccine 2009

Conference paper

Sexton A, Harman S, Shattock RJ, Ma JK-Cet al., 2009, Design, expression, and characterization of a multivalent, combination HIV microbicide, FASEB JOURNAL, Vol: 23, Pages: 3590-3600, ISSN: 0892-6638

Journal article

Wallace GS, Cheng-Mayer C, Schito ML, Fletcher P, Jenkins LMM, Hayashi R, Neurath AR, Appella E, Shattock RJet al., 2009, Human Immunodeficiency Virus Type 1 Nucleocapsid Inhibitors Impede trans Infection in Cellular and Explant Models and Protect Nonhuman Primates from Infection, JOURNAL OF VIROLOGY, Vol: 83, Pages: 9175-9182, ISSN: 0022-538X

Journal article

Rowell RL, Fairhurst D, Monahan IM, Key S, Morfesis A, Stieh D, Mitchnick M, Loxley A, Shattock RAet al., 2009, Microbicides for HIV/AIDS. 3. Observation of apparent dynamic protonation and deprotonization in CD4+ T-cell model systems., Langmuir, Vol: 25, Pages: 6954-6967, ISSN: 0743-7463

New measurements of the electrophoretic mobility of T-cell model systems have been carried out and analyzed to obtain the dynamic variation in mobility in small titration increments during separate upscale and downscale sweeps in pH. We demonstrate that a plot of plambda vs p[NaCl] has been found essential in evaluating the consistency of electrophoretic mobility measurements at different (1:1) electrolyte concentrations and show, for the first time, that electrophoretic mobility measurements as a function of pH can reflect different rates of the respective ionization and association that occur in the surface functional groups as a consequence of the different changes in the hydration-dehydration reactions involved. Differences found between the upscale and downscale sweeps suggest that it is easier to protonate a protein cell surface than to deprotonate it. The effect is most pronounced at the highest salt concentration (similar to that which exists for the cells in their native state) and becomes less pronounced as the salt concentration is lowered. The effect is interpreted as a result of the different changes in the state of hydration as a proton moves from the bulk through the double layer to a surface group and the reverse. The effect occurs with both replicating and activated T-cells. This latter result may be of biological significance and particularly relevant to HIV-1 infection, since during male-to-female transmission, the environment where most infections occur supports this protonation effect.

Journal article

Abraha A, Nankya IL, Gibson R, Demers K, Tebit DM, Johnston E, Katzenstein D, Siddiqui A, Herrera C, Fischetti L, Shattock RJ, Arts EJet al., 2009, CCR5-and CXCR4-Tropic Subtype C Human Immunodeficiency Virus Type 1 Isolates Have a Lower Level of Pathogenic Fitness than Other Dominant Group M Subtypes: Implications for the Epidemic, JOURNAL OF VIROLOGY, Vol: 83, Pages: 5592-5605, ISSN: 0022-538X

Journal article

Herrera C, Cranage M, McGowan I, Anton P, Shattock RJet al., 2009, Reverse Transcriptase Inhibitors as Potential Colorectal Microbicides, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 53, Pages: 1797-1807, ISSN: 0066-4804

Journal article

O'Keefe BR, Vojdani F, Buffa V, Shattock RJ, Montefiori DC, Bakke J, Mirsalis J, d'Andrea A-L, Hume SD, Bratcher B, Saucedo CJ, McMahon JB, Pogue GP, Palmer KEet al., 2009, Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 6099-6104, ISSN: 0027-8424

Journal article

Fletcher P, Harman S, Azijn H, Armanasco N, Manlow P, Perumal D, de Bethune M-P, Nuttall J, Romano J, Shattock Ret al., 2009, Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor., Antimicrob Agents Chemother, Vol: 53, Pages: 487-495

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide. In tissue compatibility studies, dapivirine was well tolerated by epithelial cells, T cells, macrophages, and cervical tissue explants. Dapivirine demonstrated potent dose-dependent inhibitory effects against a broad panel of HIV type 1 isolates from different clades. Furthermore, dapivirine demonstrated potent activity against a wide range of NNRTI-resistant isolates. In human cervical explant cultures, dapivirine was able not only to inhibit direct infection of mucosal tissue but also to prevent the dissemination of the virus by migratory cells. Activity was retained in the presence of semen or a cervical mucus simulant. Furthermore, dapivirine demonstrated prolonged inhibitory effects: it was able to prevent both localized and disseminated infection for as long as 6 days posttreatment. The prolonged protection observed following pretreatment of genital tissue and the lack of observable toxicity suggest that dapivirine has considerable promise as a potential microbicide candidate.

Journal article

Fischetti L, Barry SM, Hope TJ, Shattock RJet al., 2009, HIV-1 infection of human penile explant tissue and protection by candidate microbicides, AIDS, Vol: 23, Pages: 319-328, ISSN: 0269-9370

Journal article

Siddiqui AA, King DF, Buffa V, Fischetti L, Ochsenbauer-Jambor C, Gao Y, Krebs KC, Kappes JC, Arts EJ, Shattock RJet al., 2009, Evaluation of HIV-1 subtype B acute envelope-expressing infectious molecular clones, RETROVIROLOGY, Vol: 6, ISSN: 1742-4690

Journal article

Buffa V, Stieh D, Mamhood N, Hu Q, Fletcher P, Shattock RJet al., 2009, Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models, JOURNAL OF GENERAL VIROLOGY, Vol: 90, Pages: 234-243, ISSN: 0022-1317

Journal article

Donnelly L, Curran RM, Morrow RJ, Kett VL, Andrews GP, Malcolm RK, Woolfson AD, Shattock RJet al., 2009, Stable lyophilised gel vehicles for vaginal administration of recombinant C-clade HIV-1 trimeric CN54gp140, RETROVIROLOGY, Vol: 6, ISSN: 1742-4690

Journal article

Buffa V, Stieh D, Mamhood N, Hu Q, Fletcher P, Shattock RJet al., 2009, Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models, Vol: 90, Pages: 234-243, ISSN: 0022-1317

Journal article

Fletcher P, Harman S, Azijn H, Armanasco N, Manlow P, Perumal D, de Bethune MP, Nuttall J, Romano J, Shattock Ret al., 2009, Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor, Vol: 53, Pages: 487-495, ISSN: 1098-6596

Journal article

Mann JF, Cranage MP, Shattock RJ, McKay PFet al., 2008, Development of a Novel Transcytosis-Mediated HIV Envelope Vaccine Mucosal Delivery Modality, AIDS Vaccine 2008

Conference paper

Fischetti L, Shattock RJ, 2008, Monomac-1 as a Model to Study Antibody-Mediated HIV-1 Inhibition, AIDS Vaccine 2008 Conference, Publisher: MARY ANN LIEBERT INC, Pages: 48-48, ISSN: 0889-2229

Conference paper

Lisco A, Vanpouille C, Tchesnokov EP, Grivel J-C, Biancotto A, Brichacek B, Elliott J, Fromentin E, Shattock R, Anton P, Gorelick R, Balzarini J, McGuigan C, Derudas M, Götte M, Schinazi RF, Margolis Let al., 2008, Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues., Cell Host Microbe, Vol: 4, Pages: 260-270

For most viruses, there is a need for antimicrobials that target unique viral molecular properties. Acyclovir (ACV) is one such drug. It is activated into a human herpesvirus (HHV) DNA polymerase inhibitor exclusively by HHV kinases and, thus, does not suppress other viruses. Here, we show that ACV suppresses HIV-1 in HHV-coinfected human tissues, but not in HHV-free tissue or cell cultures. However, addition of HHV-6-infected cells renders these cultures sensitive to anti-HIV ACV activity. We hypothesized that such HIV suppression requires ACV phosphorylation by HHV kinases. Indeed, an ACV monophosphorylated prodrug bypasses the HHV requirement for HIV suppression. Furthermore, phosphorylated ACV directly inhibits HIV-1 reverse transcriptase (RT), terminating DNA chain elongation, and can trap RT at the termination site. These data suggest that ACV anti-HIV-1 activity may contribute to the response of HIV/HHV-coinfected patients to ACV treatment and could guide strategies for the development of new HIV-1 RT inhibitors.

Journal article

Cranage M, Sharpe S, Herrera C, Cope A, Dennis M, Berry N, Ham C, Heeney J, Rezk N, Kashuba A, Anton P, McGowan I, Shattock Ret al., 2008, Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel, PLoS Medicine, Vol: 5, ISSN: 1549-1277

BACKGROUND: The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV) drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT) inhibitor tenofovir (PMPA, 9-[(R)-2-(phosphonomethoxy) propyl] adenine monohydrate), a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV) in a well-established and standardised macaque model. METHODS AND FINDINGS: A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50) of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC), quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA) load by sensitive quantitative competitive (qc) RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test) wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from

Journal article

Haynes BF, Shattock RJ, 2008, Critical issues in mucosal immunity for HIV-1 vaccine development, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 122, Pages: 3-9, ISSN: 0091-6749

Journal article

Mesquita PMM, Wilson SS, Manlow P, Fischetti L, Keller MJ, Herold BC, Shattock RJet al., 2008, Candidate microbicide PPCM blocks human immunodeficiency virus type 1 infection in cell and tissue cultures and prevents genital herpes in a murine model, JOURNAL OF VIROLOGY, Vol: 82, Pages: 6576-6584, ISSN: 0022-538X

Journal article

van de Wijgert J, Shattock RJ, 2008, Vaginal microbicides: the importance of effective distribution, retention and coating of the mucosa, AIDS, Vol: 22, Pages: 1231-1232, ISSN: 0269-9370

Journal article

Fichorova RN, Richardson-Harman N, Alfano M, Belec L, Carbonneil C, Chen S, Cosentino L, Curtis K, Dezzutti CS, Donoval B, Doncel GF, Donaghay M, Grivel J-C, Guzman E, Hayes M, Herold B, Hillier S, Lackman-Smith C, Landay A, Margolis L, Mayer KH, Pasicznyk J-M, Pallansch-Cokonis M, Poli G, Reichelderfer P, Roberts P, Rodriguez I, Saidi H, Sassi RR, Shattock R, Cummins JEet al., 2008, Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study., Anal Chem, Vol: 80, Pages: 4741-4751

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1beta and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1beta and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal-Wallis analysis of variance with Dunn's multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences ( P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1beta determinations were lower in both s

Journal article

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