Research
Professor Martin Cranage is Emeritus Professor of Molecular Vaccinology at St George’s, University of London.
He works on understanding how experimental vaccines and other preventative approaches against HIV interact and stimulate the body’s immune responses. His specific focus is on the prevention of HIV transmission at the body's mucosal surfaces, including the vagina and rectum. He is a specialist in non-human primate immunology and vaccine challenge models.
Professor Cranage’s broad research interest lies at the interface between microbiology, in particular virology, and immunology. His research has involved the identification and characterisation of putative vaccine components, the analysis of cellular and humoral immune responses in vaccination and infection, virus pathogenesis and the development of novel diagnostic assays for a number of clinically important microorganisms.
In the 1990s Professor Cranage and his team, as part of the Medical Research Council AIDS Directed Programme, pioneered a rectal challenge model for HIV vaccine evaluation and investigated protective mechanisms elicited by inactivated virus, live attenuated viruses, virus vectors including recombinant Modified Vaccinia Vius Ankara and first-generation replication defective adenoviruses encoding SIV trangenes both alone or in combination with DNA priming (heterologous prime boost). He was actively involved in the discovery of the role of host cell proteins in vaccine protection conferred with inactivated vaccines, an interest that he has continued to pursue. Recently he convened a series of on-going international “think tank” workshops (4C programme) to identify pathways for continued research in this area.
Over the past decade at St George’s, Professor Cranage has worked closely with Professor Robin Shattock, at Imperial College London, and a large multi-national, multi-disciplinary consortium as a principal investigator on a Bill and Melinda Gates / Wellcome Trust funded Grand Challenge in Global Health programme: "Novel Antigen Design and Delivery for Mucosal Protection Against HIV-1 Infection". This afforded the opportunity to undertake highly novel parallel investigations in animal model and clinical trials ("para-clinical testing") facilitating the calibration and validation of the animal model for vaccine efficacy against virus challenge. This new paradigm reduces over-reliance on animal models and ensures that they are used to maximum benefit.
Professor Cranage as a co-principal investigator on an NIH U19 project and in collaboration with Dr Sally Sharpe at HPE, Porton demonstrated, in a model system, the utility of topical pre-exposure to tenofovir, an approved antiretroviral drug. This approach is now being evaluated in the clinic (topical pre-exposure prophylaxis).
Professor Cranage has continued to investigate mechanisms of immunity operating following vaccination with live attenuated retroviruses. Through collaboration with teams at the National Institute for Biological Standards and Control, UK led by Dr Neil Almond, the University of Amsterdam, led by Professor Ben Berkhout and University College London, led by Professor Greg Towers, including funding from the International AIDS Vaccine Initiative (IAVI), Professor Cranage’s group have investigated detailed T cell memory responses using state of the art flow cytometry methodologies and a highly novel replication conditional mutant of SIV.
Biography
Professor Cranage joined St George’s in October 2002 as Professor of Molecular Vaccinology. Prior to this he was a scientific leader at the government's Centre for Applied Microbiology and Research at Porton Down, Salisbury, where he and his team established and developed models of HIV infection and investigated a range of vaccine approaches to prevent infection.
Professor Cranage graduated from Newcastle University in microbiology in 1975 where he went on to complete a PhD on the immunology of respiratory syncytial virus infection in infants.
Following his PhD training, he took up a five year postdoctoral post at the University of Cambridge, in the Department of Pathology in the laboratory of Professor Robin Coombs, working on the development of novel rapid viral diagnostic assays. Following this he became the John Lucas Walker Senior Student in the Division of Virology based in the laboratory of Professor Tony Minson investigating cloning, expression and characterisation of glycoproteins of human cytomegalovirus. This work was one of the first demonstrations of reverse vaccinology, where putative vaccine components were cloned and expressed their ability to react with and elicit virus neutralising antibodies.
Current External memberships to professional bodies include:
Chair of the Medical Research Club (a London club founded in 1891)
Member of Faculty of 1000 (F1000)
British Society for Immunology
Microbiology Society
Previous external memberships include:
Member of the SGM's Virology Division Committee, responsible for planning conference scientific programmes.
Peer review panel for the US National Institutes of Health Special Emphasis Panels
Site reviewer for the Centres for Disease Control and Prevention in the US
Member of the MRCS College of Experts
Member of the European Network of Vaccine Research and Development User Selection Panel (EU TRANSVAC)
Member of the Policy Committee of the Microbiology Society
Publications
2014
Page M, Quatey-Papafio R, Robinson M, Hassall M, Cranage M, Stott J, Almond N. Complement-mediated virus infectivity neutralization by HLA antibodies is associated with sterilizing immunity to SIV challenge in the macaque model for HIV/AIDS. PLoS One 2014 9: e104390.
Ferguson D, Mattiuzzo G, Ham C, Stebbings R, Li B, Rose NJ, Mee ET, Smith D, Page M, Cranage MP, Almond N, Towers G, Berry NJ. Early biodistribution and persistence of a protective live attenuated SIV vaccine elicits localized innate responses in multiple lymphoid tissues. PLos One 2014 9: e104390.
2013
Lo Monaco E, Tremante E, Biswas P, Cranage MP, Zipoeto D, Beretta A, Giacomini P. Comment on “Influence of HLA-C expression level on HIV control”. Science 2013 341: 1175
Manoussaka M, Berry N, Ferguson D, Stebbings R, Robinson M, Ham C, Page M, Li B, Das AT, Berkhout B, Almond N, Cranage MP. Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions. Retrovirology. 2013, June 5; 10 (1): 59.
2012
Mann JF, Steih D, Klein K, Miranda de Stegmann D, Cranage MP, Shattock RJ, McKay PF. Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen. Journal of Controlled Release. 2012, March 10; 158(2): 240-249.
2011
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 CJ. Phase I randomised clinical trial of an HIV-1CN54, clade C, trimeric envelope vaccine candidate delivered vaginally. PLoS One. 2011, 6(9): e25165.
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 RJ. Antibody responses after intravaginal immunisation with trimeric HIV-1CN54 clade C gp140 in carbopol gel are augmented by systemic priming or boosting with an adjuvanted formulation. Vaccine, 2011, Feb 4; 29(7): 1421-1430.
Herrera C, Cranage M, McGowan I, Anton P, Shattock RJ. Colorectal microbicide design: triple combinations of reverse transcriptase inhibitors are optimal against HIV-1 in tissue explants. AIDS. 2011, Oct 23; 2516): 1971-1979.
2010
Cranage M, Fraser CA, Stevens Z, Huting J, Chang M, Jeffs SA, Seaman MS, Cope A, Cole T, Shattock RJ. Repeated vaginal administration of trimeric HIV-1 clade c gp140 induces serum and mucosal antibody responses. Mucosal Immunology. 2010, Jan; 3(1): 57-68.
Favourite publications
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, R. Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel. PLoS Med. 2008 Aug 5; 5(8).
Cranage MP, Whatmore AM, Sharpe SA, Cook N, Polyanskaya N, Leech S, Smith JD, Rud EW, Dennis MJ, Hall GA. Macaques infected with live attenuated SIVmac are protected against superinfection via the rectal mucosa. Virology. 1997, March 3; 229(1): 143-154.
Cranage MP, Kouzarides T, Bankier AT, Satchwell S, Weston K, Tomlinson P, Barrell B, Hart H, Bell SE, Minson AC, Smith GL. Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralising antibodies via its expression in recombinant vaccinia virus. EMBO J. 1986, Nov; 5(11): 3057-3063.
Collaborations
Internal
External
Dr Neil Almond, National Institute for Biological Standards and Control, UK
Dr Neil Berry, National Institute for Biological Standards and Control, UK
Professor Greg Towers, professor of molecular virology, Division of Infection and Immunity, University College London, and member of UCL MRC Centre for Medical Molecular Virology
Professor Robin Shattock, professor of mucosal infection and immunity, Department of Medicine, Imperial College, London
Dr Sally Sharpe, Public Health England, Porton Down, Salisbury
Professor Ben Berkhout, professor of virology, University of Amsterdam
Dr Atze Das, University of Amsterdam
Funding
St George’s Researcher Development Support Scheme
Awarded to Cranage M
October 2012 to August 2013, £38,736
Molecular vaccine development (staff, infrastructure, equipment and consumables)
Private endowment to St George's, awarded to Cranage M (PI)
The Hotung Trust
January 2002 to November 2012, £3,438,562
EUROPRISE Network of Excellence on microbicides and vaccines
St George's scientific team leaders: Shattock R, Cranage M, Ma J, Lewis D
The European Commission
January 2007 to December 2011, £67,000
EUROPRISE Network of Excellence on microbicides and vaccines
– Modelling HIV and SIV neutralisation at the colo-rectal mucosal surface (PhD studentship)
The European Commission
January 2007 to April 2011, £78,500
Grand Challenges in Global Health – Novel antigen design and delivery for mucosal protection against HIV
Awarded to Cranage M (co-applicant and PI for Immunology Core)
Bill & Melinda Gates Foundation and The Wellcome Trust
January 2005 to March 2013, £335,000
Teaching
Professor Cranage delivers an annual HIV vaccines lecture at the University of Bath.
He supervises one, and co-supervises four, postgraduate research students.
