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  • Journal article
    Lewis DJM, Wang Y, Huo Z, Giemza R, Babaahmady K, Rahman D, Shattock RJ, Singh M, Lehner Tet al., 2014,

    Effect of Vaginal Immunization with HIVgp140 and HSP70 on HIV-1 Replication and Innate and T Cell Adaptive Immunity in Women

    , JOURNAL OF VIROLOGY, Vol: 88, Pages: 11648-11657, ISSN: 0022-538X
  • Journal article
    Klein K, Mann JFS, Rogers P, Shattock RJet al., 2014,

    Polymeric penetration enhancers promote humoral immune responses to mucosal vaccines

    , JOURNAL OF CONTROLLED RELEASE, Vol: 183, Pages: 43-50, ISSN: 0168-3659
  • Journal article
    Walters AA, Kinnear E, Shattock RJ, McDonald JU, Caproni LJ, Porter N, Tregoning JSet al., 2014,

    Comparative analysis of enzymatically produced novel linear DNA constructs with plasmids for use as DNA vaccines

    , Gene Therapy, Vol: 21, Pages: 645-652, ISSN: 1476-5462
  • Journal article
    Malcolm RK, Lowry D, Boyd P, Geer L, Veazey RS, Goldman L, Klasse PJ, Shattock RJ, Moore JPet al., 2014,

    Pharmacokinetics of a CCR5 inhibitor in rhesus macaques following vaginal, rectal and oral application

    , JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 69, Pages: 1325-1329, ISSN: 0305-7453
  • Journal article
    Forbes CJ, Mccoy CF, Murphy DJ, Woolfson AD, Moore JP, Evans A, Shattock RJ, Malcolm RKet al., 2014,

    Modified Silicone Elastomer Vaginal Gels for Sustained Release of Antiretroviral HIV Microbicides

    , JOURNAL OF PHARMACEUTICAL SCIENCES, Vol: 103, Pages: 1422-1432, ISSN: 0022-3549
  • Journal article
    Herrera C, Shattock RJ, 2014,

    Candidate Microbicides and Their Mechanisms of Action

    , MICROBICIDES FOR PREVENTION OF HIV INFECTION, Vol: 383, Pages: 1-25, ISSN: 0070-217X
  • Journal article
    Mann JFS, Mckay PF, Fiserova A, Klein K, Cope A, Rogers P, Swales J, Seaman MS, Combadiere B, Shattock RJet al., 2014,

    Enhanced immunogenicity of an HIV-1 DNA vaccine delivered with electroporation via combined intramuscular and intradermal routes

    , Journal of Virology, Vol: 88, Pages: 6959-6969, ISSN: 1098-5514

    It is accepted that an effective prophylactic HIV-1 vaccine is likely to have the greatest impact on viral transmission rates. As previous reports have implicated DNA-priming, protein boost regimens to be efficient activators of humoral responses, we sought to optimize this regimen to further augment vaccine immunogenicity. Here we evaluated single versus concurrent intradermal (i.d.) and intramuscular (i.m.) vaccinations as a DNA-priming strategy for their abilities to elicit humoral and cellular responses against a model HIV-1 vaccine antigen, CN54-gp140. To further augment vaccine-elicited T and B cell responses, we enhanced cellular transfection with electroporation and then boosted the DNA-primed responses with homologous protein delivered subcutaneously (s.c.), intranasally (i.n.), i.m., or transcutaneously (t.c.). In mice, the concurrent priming regimen resulted in significantly elevated gamma interferon T cell responses and high-avidity antigen-specific IgG B cell responses, a hallmark of B cell maturation. Protein boosting of the concurrent DNA strategy further enhanced IgG concentrations but had little impact on T cell reactivity. Interestingly protein boosting by the subcutaneous route increased antibody avidity to a greater extent than protein boosting by either the i.m., i.n., or t.c. route, suggesting that this route may be preferential for driving B cell maturation. Using an alternative and larger animal model, the rabbit, we found the concurrent DNA-priming strategy followed by s.c. protein boosting to again be capable of eliciting high-avidity humoral responses and to also be able to neutralize HIV-1 pseudoviruses from diverse clades (clades A, B, and C). Taken together, we show that concurrent multiple-route DNA vaccinations induce strong cellular immunity, in addition to potent and high-avidity humoral immune responses.
  • Journal article
    Jones C, Quinn K, Miller A, O'Farrell S, Legg K, Shattock R, McCormack Set al., 2014,

    What are the best methods to recruit healthy volunteers into HIV vaccine trials?

    , HIV MEDICINE, Vol: 15, Pages: 146-146, ISSN: 1464-2662
  • Journal article
    Jones C, Kaye S, Shattock R, Fidler Set al., 2014,

    Can we measure HIV viral load in mucosal secretions in men?

    , HIV MEDICINE, Vol: 15, Pages: 145-145, ISSN: 1464-2662
  • Journal article
    McKay PF, Cope AV, Mann JFS, Joseph S, Esteban M, Tatoud R, Carter D, Reed SG, Weber J, Shattock RJet al., 2014,

    Glucopyranosyl lipid A adjuvant significantly enhances HIV specific T and B cell responses elicited by a DNA-MVA-protein vaccine regimen

    , PLOS One, Vol: 9, ISSN: 1932-6203

    Using a unique vaccine antigen matched and single HIV Clade C approach we have assessed the immunogenicity of a DNApoxvirus-proteinstrategy in mice and rabbits, administering MVA and protein immunizations either sequentially orsimultaneously and in the presence of a novel TLR4 adjuvant, GLA-AF. Mice were vaccinated with combinations of HIV env/gag-pol-nef plasmid DNA followed by MVA-C (HIV env/gag-pol-nef) with HIV CN54gp140 protein (+/2GLA-AF adjuvant) andeither co-administered in different muscles of the same animal with MVA-C or given sequentially at 3-week intervals. TheDNA prime established a population of B cells that were able to mount a statistically significant anamnestic response to theboost vaccines. The greatest antigen-specific antibody response was observed in animals that received all vaccinecomponents. Moreover, a high proportion of the total mucosal IgG (20 – 50%) present in the vaginal vault of thesevaccinated animals was vaccine antigen-specific. The potent elicitation of antigen-specific immune responses to this vaccinemodality was also confirmed in rabbits. Importantly, co-administration of MVA-C with the GLA-AF adjuvanted HIVCN54gp140 protein significantly augmented the antigen-specific T cell responses to the Gag antigen, a transgene productexpressed by the MVA-C vector in a separate quadriceps muscle. We have demonstrated that co-administration of MVA andGLA-AF adjuvanted HIV CN54gp140 protein was equally effective in the generation of humoral responses as a sequentialvaccination modality thus shortening and simplifying the immunization schedule. In addition, a significant further benefit ofthe condensed vaccination regime was that T cell responses to proteins expressed by the MVA-C were potently enhanced,an effect that was likely due to enhanced immunostimulation in the presence of systemic GLA-AF.

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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