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  • 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
    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
    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
    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
    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
  • Book chapter
    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

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