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

286 results found

Ruffin N, Borggren M, Euler Z, Fiorino F, Grupping K, Hallengard D, Javed A, Mendonca K, Pollard C, Reinhart D, Saba E, Sheik-Khalil E, Skold A, Ziglio S, Scarlatti G, Gotch F, Wahren B, Shattock RJet 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

Journal article

Huang W, Hu K, Luo S, Zhang M, Li C, Jin W, Liu Y, Griffin GE, Shattock RJ, Hu Qet al., 2012, Herpes Simplex Virus Type 2 Infection of Human Epithelial Cells Induces CXCL9 Expression and CD4(+) T Cell Migration via Activation of p38-CCAAT/Enhancer-Binding Protein-beta Pathway, JOURNAL OF IMMUNOLOGY, Vol: 188, Pages: 6247-6257, ISSN: 0022-1767

Journal article

Malcolm RK, Veazey RS, Geer L, Lowry D, Fetherston SM, Murphy DJ, Boyd P, Major I, Shattock RJ, Klasse PJ, Doyle LA, Rasmussen KK, Goldman L, Ketas TJ, Moore JPet al., 2012, Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 56, Pages: 2251-2258, ISSN: 0066-4804

Journal article

Pattani A, McKay PF, Curran RM, McCaffrey J, Gupta PN, Lowry D, Kett VL, Shattock RJ, McCarthy HO, Malcolm RKet al., 2012, Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form, VACCINE, Vol: 30, Pages: 2778-2785, ISSN: 0264-410X

Journal article

Moore JP, Klasse PJ, Veazey RA, Shattock RJ, Malcolm RKet al., 2012, Towards Coitally-Independent Microbicides: Studies with Vaginal Rings and Silicone-Based Gel Delivery Systems, 13th Annual International Meeting of the Institute of Human Virology, Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: 43-43, ISSN: 1525-4135

Conference paper

Mann JFS, Stieh D, Klein K, de Stegmann DSM, Cranage MP, Shattock RJ, McKay PFet al., 2012, Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen, JOURNAL OF CONTROLLED RELEASE, Vol: 158, Pages: 240-249, ISSN: 0168-3659

Journal article

Harman SJ, Herrera C, Armanasco N, Nuttall J, Shattock RJet al., 2012, Pre-clinical evaluation of the HIV-1 fusion inhibitor L'644 as a potential candidate microbicide., Antimicrobial Agents and Chemotherapy

Topical blockade of the gp41 fusogenic protein of HIV-1 is one possible strategy by which microbicides could prevent HIV transmission, working early against infection, by inhibiting viral entry into host cells. In this study we examined the potential of gp41 fusion inhibitors (FIs) as candidate anti-HIV microbicides. Preclinical evaluation of four FIs, C34, T20, T1249 and L'644, was performed using cellular and ex vivo genital and colorectal tissue explant models. Increased and sustained activity was detected for L'644, a cholesterol derivatized version of C34 relative to the other FIs. The higher potency of L'644 was further increased with sustained exposure of cells or tissue to the compound. The activity of L'644 was not affected by biological fluids and the compound was still active when tissue explants where treated after viral exposure. L'644 was also more active than other FIs against a viral escape mutant resistant to reverse transcriptase inhibitors (RTIs), demonstrating the potential of L'644 to be included as part of a multi-active ARV-combination based microbicide. These data support further development of L'644 for microbicide application.

Journal article

Huang X, Jin W, Hu K, Luo S, Du T, Griffin GE, Shattock RJ, Hu Qet al., 2012, Highly conserved HIV-1 gp120 glycans proximal to CD4-binding region affect viral infectivity and neutralizing antibody induction, VIROLOGY, Vol: 423, Pages: 97-106, ISSN: 0042-6822

Journal article

McFadden K, Fletcher P, Rossi F, Kantharaju, Umashankara M, Pirrone V, Rajagopal S, Gopi H, Krebs FC, Martin-Garcia J, Shattock RJ, Chaiken Iet al., 2012, Antiviral Breadth and Combination Potential of Peptide Triazole HIV-1 Entry Inhibitors, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 56, Pages: 1073-1080, ISSN: 0066-4804

Journal article

Van Roey GA, Arias MA, Tregoning JS, Rowe G, Shattock RJet al., 2012, Thymic stromal lymphopoietin (TSLP) acts as a potent mucosal adjuvant for HIV-1 gp140 vaccination in mice, European Journal of Immunology, Vol: 42, Pages: 353-363, ISSN: 1521-4141

The development of a successful vaccine against HIV is likely to require the induction of strong and long-lasting humoral immune responses at the mucosal portal of virus entry. Hence, the design of a vaccine strategy able to induce mucosal antibodies and in particular specific IgA, may be crucial to providing immune protection. Nasal immunisation is known to induce specific IgG and IgA responses in the cervicovaginal mucosa; however, there is an urgent need for the development of safe, effective and accessible mucosal adjuvants for nasal application in humans. To reduce the potential for adverse events associated with some nasal adjuvants, we have assessed whether the B-cell-activating cytokines APRIL, BAFF and TSLP enhance humoral immune responses to HIV-1 gp140. Following intranasal immunisation, TSLP but not APRIL or BAFF induced strong humoral responses both in serum and mucosa. The adjuvant effect of TSLP on humoral responses was similar to that of cholera toxin (CT). The use of TSLP as an adjuvant skewed both the cellular and humoral immune responses towards Th2 cells. This is the first time that TSLP has been demonstrated to have a positive effect as a mucosal adjuvant, and specifically to promote mucosal and systemic responses to HIV gp140.

Journal article

Shattock RJ, Rosenberg Z, 2012, Microbicides: topical prevention against HIV., Cold Spring Harb Perspect Med, Vol: 2

Microbicides represent a potential intervention strategy for preventing HIV transmission. Vaginal microbicides would meet the need for a discreet method that women could use to protect themselves against HIV. Although early-generation microbicides failed to demonstrate efficacy, newer candidates are based on more potent antiretroviral (ARV) products. Positive data from the CAPRISA 004 trial of tenofovir gel support use in women and represent a turning point for the field. This article reviews current progress in development of ARV-based microbicides. We discuss the consensus on selection criteria, the potential for drug resistance, rationale for drug combinations, and the use of pharmacokinetic (PK)/pharmacodynamic (PD) assessment in product development. The urgent need for continued progress in development of formulations for sustained delivery is emphasized. Finally, as the boundaries between different prevention technologies become increasingly blurred, consideration is given to the potential synergy of diverse approaches across the prevention landscape.

Journal article

Veazey RS, Shattock RJ, Klasse PJ, Moore JPet al., 2012, Animal Models for Microbicide Studies, CURRENT HIV RESEARCH, Vol: 10, Pages: 79-87, ISSN: 1570-162X

Journal article

Herrera C, Shattock RJ, 2012, Potential Use of Protease Inhibitors as Vaginal and Colorectal Microbicides, CURRENT HIV RESEARCH, Vol: 10, Pages: 42-52, ISSN: 1570-162X

Journal article

Shattock R, Rosenberg Z, 2012, Microbicides: Topical Prevention against HIV, HIV: From Biology to Prevention and Treatment, Editors: Bushman, Nabel, Swanstrom, Publisher: Cold Spring Harbor Laboratory Press, Pages: 505-521

Book chapter

Forbes CJ, Lowry D, Geer L, Veazey RS, Shattock RJ, Klasse PJ, Mitchnick M, Goldman L, Doyle LA, Muldoon BCO, Woolfson AD, Moore JP, Malcolm RKet al., 2011, Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc, JOURNAL OF CONTROLLED RELEASE, Vol: 156, Pages: 161-169, ISSN: 0168-3659

Journal article

Kelly CG, Shattock RJ, 2011, Specific microbicides in the prevention of HIV infection, JOURNAL OF INTERNAL MEDICINE, Vol: 270, Pages: 509-519, ISSN: 0954-6820

Journal article

Herrera C, Cranage M, McGowan I, Anton P, Shattock RJet al., 2011, Colorectal microbicide design: triple combinations of reverse transcriptase inhibitors are optimal against HIV-1 in tissue explants, AIDS, Vol: 25, Pages: 1971-1979, ISSN: 0269-9370

Journal article

Huang X, Jin W, Griffin GE, Shattock RJ, Hu Qet al., 2011, Removal of two high-mannose N-linked glycans on gp120 renders human immunodeficiency virus 1 largely resistant to the carbohydrate-binding agent griffithsin, JOURNAL OF GENERAL VIROLOGY, Vol: 92, Pages: 2367-2373, ISSN: 0022-1317

Journal article

Veazey R, Siddiqui AA, Buffa V, Fischetti L, King D, Shattock RJet al., 2011, Evaluation of Mucosal Immunization Routes for Induction of Vaginal Humoral Immunity in Macaques., Conference on AIDS Vaccine, Publisher: MARY ANN LIEBERT INC, Pages: A68-A68, ISSN: 0889-2229

Conference paper

Van Roey GA, Arias M, Tregoning JS, Shattock RJet al., 2011, TSLP: A Potential New Mucosal Adjuvant for Intranasal Immunisation with GP140, Conference on AIDS Vaccine, Publisher: MARY ANN LIEBERT INC, Pages: A68-A68, ISSN: 0889-2229

Conference paper

Lewis DJ, Fraser CA, Mahmoud AN, Wiggins RC, Woodrow M, Cope A, Cai C, Giemza R, Jeffs SA, Manoussaka M, Cole T, Cranage MP, Shattock RJ, Lacey CJet al., 2011, Phase I randomised clinical trial of an HIV-1(CN54), clade C, trimeric envelope vaccine candidate delivered vaginally, PLoS ONE, Vol: 6, ISSN: 1932-6203

We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women.

Journal article

Van Roey G, Arias M, Tregoning J, Shattock RJet al., 2011, TSLP, a potential new mucosal adjuvant for intranasal immunisation with HIV-1 gp140, AIDS Vaccine Conference, Bangkok, Thailand

Poster

Liard C, Munier S, Arias M, Joulin-Giet A, Bonduelle O, Duffy D, Shattock RJ, Verrier B, Combadiere Bet al., 2011, Targeting of HIV-p24 particle-based vaccine into differential skin layers induces distinct arms of the immune responses, VACCINE, Vol: 29, Pages: 6379-6391, ISSN: 0264-410X

Journal article

Veazey RS, Klasse PJ, Shattock RJ, Pope M, Kirijan JC, Jones J, Ketas T, Marx PA, Burton DR, Moore JPet al., 2011, Vaginal application of anti-gp120 monocloncal antibody b12 prevents SHIV-162P vaginal transmission to macaques., Pages: 51-57

Journal article

Shattock RJ, Warren M, McCormack S, Hankins CAet al., 2011, Turning the Tide Against HIV, SCIENCE, Vol: 333, Pages: 42-43, ISSN: 0036-8075

Journal article

Donnelly L, Curran RM, Tregoning JS, McKay PF, Cole T, Morrow RJ, Kett VL, Andrews GP, Woolfson AD, Malcolm RK, Shattock RJet al., 2011, Intravaginal immunization using the recombinant HIV-1 clade-C trimeric envelope glycoprotein CN54gp140 formulated within lyophilized solid dosage forms, Vaccine, Vol: 29, Pages: 4512-4520, ISSN: 1873-2518

Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunized with lyophilized equivalents of (i) RSVs, (ii) modified versions of the RSVs more suited to lyophilization (sodium carboxymethyl cellulose (NaCMC)-based gels) and (iii) Carbopol® gel, all containing CN54gp140. NaCMC-based LSDFs provided significantly enhanced antigen stability compared to aqueous-based RSVs. Rheological analysis indicated the NaCMC-based LSDFs would offer enhanced vaginal retention in woman compared to more conventional vaginal gel formulations. All LSDFs were well tolerated in the mouse model. Following i.vag administration, all LSDFs boosted systemic CN54gp140-specific antibody responses in sub-cutaneously primed mice. Induction of CN54gp140-specific antibody responses in the female genital tract was evident. Of all the LSDFs the fastest releasing which was lyophilized Carbopol® gel elicited immune responses comparable to buffer instillation of antigen suggesting that rather than slower sustained release, initial high burst release from the LSDFs may suffice. The boosting of specific immune responses upon i.vag administration indicates that LSDFs are viable mucosal vaccine delivery modalities promoting antigen stability and facilitating intimate exposur

Journal article

Brinckmann S, da Costa K, van Gils MJ, Hallengard D, Klein K, Madeira L, Mainetti L, Palma P, Raue K, Reinhart D, Reudelsterz M, Ruffin N, Seifried J, Schaefer K, Sheik-Khalil E, Skold A, Uchtenhagen H, Vabret N, Ziglio S, Scarlatti G, Shattock R, Wahren B, Gotch Fet al., 2011, Rational design of HIV vaccines and microbicides: report of the EUROPRISE network annual conference 2010, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 9

Journal article

Cranage MP, Fraser CA, Cope A, Mckay PF, Seaman MS, Cole T, Mahmoud AN, Hall J, Giles E, Voss G, Page M, Almond N, Shattock RJet al., 2011, Antibody responses after intravaginal immunisation with trimeric HIV-1(CN54) clade C gp140 in Carbopol gel are augmented by systemic priming or boosting with an adjuvanted formulation, Vaccine, Vol: 29, Pages: 1421-1430, ISSN: 0264-410X

Optimum strategies to elicit and maintain antibodies at mucosal portals of virus entry are critical for the development of vaccines against human immunodeficiency virus (HIV). Here we show in non-human primates that a novel regimen of repeated intravaginal delivery of a non-adjuvanted, soluble recombinant trimeric HIV-1(CN54) clade C envelope glycoprotein (gp140) administered in Carbopol gel can prime for B-cell responses even in the absence of seroconversion. Following 3 cycles of repeated intravaginal administration, throughout each intermenses interval, 3 of 4 macaques produced or boosted systemic and mucosally-detected antibodies upon intramuscular immunisation with gp140 formulated in AS01 adjuvant. Reciprocally, a single intramuscular immunisation primed 3 of 4 macaques for antibody boosting after a single cycle of intravaginal immunisation. Virus neutralising activity was detected against clade C and clade B HIV-1 envelopes but was restricted to highly neutralisation sensitive pseudoviruses. (C) 2010 Elsevier Ltd. All rights reserved.

Journal article

Arias MA, Loxley A, Eatmon C, Van Roey G, Fairhurst D, Mitchnick M, Dash P, Cole T, Wegmann F, Sattentau Q, Shattock Ret al., 2011, Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen, VACCINE, Vol: 29, Pages: 1258-1269, ISSN: 0264-410X

Journal article

Grivel J-C, Shattock RJ, Margolis LB, 2011, Selective transmission of R5 HIV-1 variants: where is the gatekeeper?, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 9, ISSN: 1479-5876

Journal article

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