Publications
382 results found
McKay PF, King DF, Carter D, et al., 2011, Vaccine Antigen Immunity Is Enhanced by Optimized TLR4 and TLR7/8 Adjuvant Combinations in Mini-Pigs Inoculated via a Systemic but not a Mucosal Route, AIDS Vaccine 2011, Publisher: Mary Ann Liebert, Inc.
Pattani A, McKay PF, Donnelly RF, et al., 2011, Microneedle Mediated Intradermal Delivery of Adjuvanted Recombinant HIV-1 CN54gp140 Effectively Primes Mucosal Boost Inoculations, AIDS Vaccine 2011, Publisher: Mary Ann Liebert, Inc.
Mann JF, McKay PF, Patel RK, et al., 2011, Mucosally Applied HIV gp140 DNA Prime/Protein Boost Strategies Generate Strong Serum and Mucosal Antigen-Specific Humoral Responses in Mice, AIDS Vaccine 2011, Publisher: Mary Ann Liebert, Inc.
McKay PF, Cope A, Swales J, et al., 2011, HIV CN54gp140 +GLA Significantly Enhances VaccineAntigen-Specific T and B Cell Immune Responses After Priming with DNA and MVA, AIDS Vaccine 2011, Publisher: Mary Ann Liebert, Inc.
Whaley KJ, Hanes J, Shattock R, et al., 2010, Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines., Antiviral Res, Vol: 88 Suppl 1, Pages: S55-S66
The HIV-1 epidemic remains unchecked despite existing technology; vaccines and microbicides in development may help reverse the epidemic. Reverse transcriptase inhibitors (RTIs) formulated in gels tenofovir (TFV) and IVRs (dapivirine) are under clinical development. While TFV or similar products may prove successful for HIV-1, alternatives to RTIs may provide additional benefits, e.g., broader STI prevention. Biopharmaceutical agents under development as microbicides include cyanovirin, RANTES analogues, commensals, and Mabs. Cost of manufacturing biopharmaceuticals has been reduced and they can be formulated into tablets, films, and IVRs for vaginal delivery. Nanotechnology offers a novel approach to formulate microbicides potentially leading to uniform epithelial delivery. Delivery through vaginal mucus may be possible by controlling nanoparticle size and surface characteristics. Combining prevention modalities may be the most effective means of preventing STI transmission, importantly, codelivery of microbicides and vaccines has demonstrated. Finally, the safety of microbicide preparations and excipients commonly used can be assessed using a mouse/HSV-2 susceptibility model. Screening of new microbicide candidates and formulation excipients may avoid past issues of enhancing HIV-1 transmission. This article forms part of a special supplement covering several presentations on novel microbicide formulations from the symposium on "Recent Trends in Microbicide Formulations" held on 25 and 26 January 2010, Arlington, VA.
Hu Q, Huang X, Shattock RJ, 2010, C-C chemokine receptor type 5 (CCR5) utilization of transmitted and early founder human immunodeficiency virus type 1 envelopes and sensitivity to small-molecule CCR5 inhibitors, JOURNAL OF GENERAL VIROLOGY, Vol: 91, Pages: 2965-2973, ISSN: 0022-1317
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- Citations: 15
Patel R, Mann JFS, McKay PF, et al., 2010, Optimisation of different cationic complexes for mucosal delivery of an HIV-1 gp140 plasmid DNA vaccine, EUROPRISE - Rational Design of HIV Vaccines and Microbicides
McKay PF, Mann JFS, Cope AV, et al., 2010, Dramatic enhancement of gp140-specific mucosal IgA responses in mice following intramuscular DNA prime-intranasal adjuvant-free protein boost., 6th Annual Grand Challenges in Global Health Meeting
Borrow P, Shattock RJ, Vyakarnam A, 2010, Innate immunity against HIV: a priority target for HIV prevention research, RETROVIROLOGY, Vol: 7
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- Citations: 41
Wahren B, Biswas P, Borggren M, et al., 2010, Rational design of HIV vaccine and microbicides: report of the EUROPRISE annual conference, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 8
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- Citations: 4
King D, McKay PF, van Roey G, et al., 2010, Progress in the Development of a Transgenic Rabbit Model for the Testing of Anti-HIV Microbicides, Microbicides 2010
Harman SJ, Herrera C, Armanasco N, et 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
Harman SJ, Armanasco N, Stieh D, et al., 2010, A preclinical evaluation of the small molecule entry inhibitor DS003 as a potential microbicide (oral presentation given by R Shattock), Microbicides 2010
Jespers V, Harandi AM, Hinkula J, et al., 2010, Assessment of mucosal immunity to HIV-1, EXPERT REVIEW OF VACCINES, Vol: 9, Pages: 381-394, ISSN: 1476-0584
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- Citations: 19
Harandi AM, Medaglini D, Shattock RJ, 2010, Vaccine adjuvants: A priority for vaccine research, VACCINE, Vol: 28, Pages: 2363-2366, ISSN: 0264-410X
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- Citations: 72
Harman SJ, Herrera C, Armanasco N, et 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
Cranage MP, Fraser CA, Stevens Z, et 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
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- Citations: 33
Curran RM, Donnelly L, Morrow RJ, et 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
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- Citations: 34
Richardson-Harman N, Lackman-Smith C, Fletcher PS, et 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
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- Citations: 47
Stieh DJ, Fischetti L, Buff V, et al., 2009, P04-30. Sorting of infectious and non-infectious viral particles by Env-specific mAb, Retrovirology, Vol: 6
Morrow RJ, Donnelly L, Curran RM, et al., 2009, P11-12. A novel vaginal ring device for the sustained delivery of recombinant C-clade HIV-1 CN54gp140, Retrovirology, Vol: 6
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- Citations: 2
Mann JF, Miranda de Stegmann DS, Klein K, et 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
Buffa V, Klein K, Tregoning J, et al., 2009, P02-03. Screening of potential adjuvants for induction of pro-IgA factors, Retrovirology, Vol: 6
Sexton A, Harman S, Shattock RJ, et al., 2009, Design, expression, and characterization of a multivalent, combination HIV microbicide, FASEB JOURNAL, Vol: 23, Pages: 3590-3600, ISSN: 0892-6638
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- Citations: 42
Wallace GS, Cheng-Mayer C, Schito ML, et al., 2009, Human Immunodeficiency Virus Type 1 Nucleocapsid Inhibitors Impede <i>trans</i> Infection in Cellular and Explant Models and Protect Nonhuman Primates from Infection, JOURNAL OF VIROLOGY, Vol: 83, Pages: 9175-9182, ISSN: 0022-538X
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- Citations: 31
Rowell RL, Fairhurst D, Monahan IM, et 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.
Abraha A, Nankya IL, Gibson R, et 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
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- Citations: 78
Herrera C, Cranage M, McGowan I, et al., 2009, Reverse Transcriptase Inhibitors as Potential Colorectal Microbicides, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 53, Pages: 1797-1807, ISSN: 0066-4804
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- Citations: 75
O'Keefe BR, Vojdani F, Buffa V, et 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
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- Citations: 211
Fletcher P, Harman S, Azijn H, et 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.
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