| Dr Ann Rawkins |
Research interestsMy current role is a Scientific Leader providing scientific direction to the TB research programme at HPA Porton. The broad aim of the group is to study the physiology, molecular genetics and pathogenesis of M. tuberculosis in order to identify and further develop vaccine and/or therapeutic targets and to contribute to the development of strategies to control TB in humans by evaluation of vaccines and therapies in specialised aerosol-challenge in-vivo models. The vaccine evaluation team are internationally renowned and collaborate with the majority of TB vaccine developers world-wide. My particular expertise is in novel vaccine development and evaluation and in aerobiology as applied to in-vivo model development. I provide expertise on in-vivo evaluation of TB vaccines to several international bodies including a major EU-funded TB vaccine consortium and the newly formed TB Vaccine Initiative (a non-profit organization aimed at facilitating new TB vaccine development) and the NIH TB vaccine testing and research materials Contract. Publications58 Peer Reviewed Publications, in the name of Williams, and 1 book chapter in the name of Rawkins, listed below.
Michael J. Brennan, Clagett B, Chen V, Fitzgerald H, Williams A, Izzo A and Barker L (2012) Preclinical Evidence for Implementing a Prime-boost Vaccine Strategy for Tuberculosis. Vaccine In press
Naomi F Walker, Simon O Clark, Tolullah Oni, Nuria Andreu, Liku Tezera, Shivani Singh, Luísa Saraiva, Bernadette Pedersen, Dominic Kelly, Julia Tree, Jeanine M D’Armiento, Graeme Meintjes, Francesco Mauri, Ann Williams, Robert J Wilkinson, Jon S Friedland & Paul Elkington. (2012) Doxycycline and HIV infection suppress tuberculosis induced matrix metalloproteinases. American Journal of Respiratory and Critical Care Medicine. In press
Julia A. Tree, Jyoti Patel, Ruth E. Thom, Michael J. Elmore, Hubert Schäfer, Ann Williams, Philip D. Marsh. Temporal changes in the cytokine response of guinea pigs following BCG vaccination. Vaccine. 2010 Nov 23;28(50):7979-86
Sharpe SA, H McShane, MJ Dennis, R J Basaraba, F Gleeson, G Hall, A McIntyre, K Gooch, S Clark, N E R Beveridge, E. Nuth, A White, A Marriott, S Dowall, AVS Hill, A Williams, & PD Marsh (2010) Establishment of an aerosol challenge model of tuberculosis in rhesus macaques, and an evaluation of endpoints for vaccine testing. Clinical & Vaccine Immunology;17(8):1170-82.
Ann Williams, Yper Hall, Ian M. Orme. Evaluation of new vaccines for tuberculosis in the guinea pig model. Tuberculosis 89 (2009) 389–397.
S.A. Sharpe, E. Eschelbach , R.J. Basaraba , F. Gleeson , G.A. Hall , A. McIntyre , A. Williams, S.L. Kraft, S. Clark, K. Gooch, G. Hatch, I.M. Orme, P.D. Marsh, M.J. Dennis. Determination of lesion volume by MRI and stereology in a macaque model of tuberculosis, Tuberculosis (2009), doi:10.1016/j.tube.2009.09.002
Vipond J, Cross ML, Lambeth MR, Clark S, Aldwell FE, Williams A. Immunogenicity of orally-delivered lipid-formulated BCG vaccines and protection against Mycobacterium tuberculosis infection. Microbes Infect. 2008;10:1577-81.
Clark S, Cross ML, Nadian A, Vipond J, Court P, Williams A, Hewinson RG, Aldwell FE, Chambers MA. 2008 Vaccine 26;5791-7
Clark S, Cross ML, Nadian A, Vipond J, Court P, Williams A, Hewinson RG, Aldwell FE, Chambers MA. Oral vaccination of guinea pigs with Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine in a lipid matrix protects against aerosol infection with virulent M. bovis. 2008 Infect Immun. 76;3771-6.
Farahnaz Movahedzadeh, Ann Williams, Simon Clark, Graham Hatch, Debbie Smith, Joanna Bacon, Tanya parish, Neil Stoker. Construction of a severely attenuated mutant of Mycobacterium tuberculosis for reducing risk to laboratory workers. 2008, Tuberculosis. 88;375-81
Bennett A, Rawkins A, Lever M.S. Aerosol infection of small animals – safety considerations. In: Anthology of Biosafety X: Animal Biosafety. Ed J.L. Richmond, ABSA Publication. 2007
Julia Vipond, Richard Vipond, Emma Allen-Vercoe, Simon O. Clark, Graham J. Hatch, Karen E. Gooch, Joanna Bacon, Toby Hampshire, Helen Shuttleworth, Nigel P Minton, Karen Blake, Ann Williams and Philip D. Marsh. Selection of novel TB vaccine candidates and their evaluation as DNA vaccines against aerosol challenge. 2006 Vaccine, 24:6340-50.
Rajko Reljic, Ann Williams and Juraj Ivanyi Mucosal immunotherapy of tuberculosis: Is there a value in passive IgA? 2006 Tuberculosis 86: 179-190.
Julia Vipond, Simon O. Clark, Graham J. Hatch, Richard Vipond, Else Marie Aggera, Julia A. Tree, Ann Williams and Philip D. Marsh. Re-formulation of selected DNA vaccine candidates and their evaluation as protein vaccines using a guinea pig aerosol infection model of tuberculosis. 2006 Tuberculosis 86, 218-224.
Martin C, Williams A, Hernandez-Pando R, Cardona PJ, Gormley E, Bordat Y, Soto CY, Clark SO, Hatch GJ, Aguilar D, Ausina V, Gicquel B. The Mycobacterium tuberculosis phoP strain SO2 is highly attenuated and confers protective immunity against tuberculosis in the guinea pig superior to the BCG vaccine. 2006 Vaccine 24 3408-3419.
Else Marie Agger, Graham Hatch, Ann Williams, Ida Rosenkrands, Anja Olsen, Claire S. Andersen, Karen Korsholm and Peter Andersen. Protective immunity to Tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31 2006 Vaccine, 24:5452-60
Eleanor Roy, Dharshan De Silva, Simon O. Clark, Evangelos Stavropoulos, Vasan Sambandamurthy, William B. Jacobs Jr, Ann Williams, Brigitta Stockinger, M. Joseph Colston and Ricardo E. Tascon Induction of high levels of protective immunity after vaccination using dendritic cells infected with auxotrophic mutants of Mycobacterium tuberculosis. 2006 Immunology Letters. 102:196-199.
JA Tree, ME Elmore, S Javed, A Williams, PD Marsh. The development of a guinea pig immune-related microarray and its use to define the host response following BCG vaccination. Infection and Immunity.2006 74:1436-1441
Rajko Reljic, Simon Clark, Ann Williams, Gustavo Falero-Diaz, Mahavir Singh, Stephen Challacombe, Philip Marsh and Juraj Ivanyi. Intranasal IFN? extends passive IgA anibody protection of mice against Mycobacterium tuberculosis lung infection. Clinical Experimental Imunology. 2006 143, 467-473.
Ariane Rodríguez, Anna Tjärnlund, Juraj Ivanji, Mahavir Singh, Irene García, Ann Williams, Philip D. Marsh, Marita Troye-Blomberg and Carmen Fernández . Role of IgA in the defense against respiratory infections IgA deficient mice display increased susceptibility to intranasal infection with Mycobacterium bovis BCG. 2005 Vaccine 23, 2565- 2572.
Ann Williams, Graham J Hatch, Simon O Clark, Karen E Gooch, Kim A Hatch, Graham A Hall, Kris Huygen, Tom HM Ottenhoff, Kees LMC Franken, Peter Andersen, T. Mark Doherty, Stefan H.E. Kaufmann, Leander Grode, Peter Seiler, Carlos Martin, Brigitte Gicquel, Stewart T. Cole, Priscille Brodin, Alexander S. Pym, Wilfried Dalemans, Joe Cohen, Yves Lobet, Nilu Goonetilleke, Helen McShane, Adrian Hill, Tanya Parish, Debbie Smith, Neil Stoker, Douglas B Lowrie, Gunilla Källenius, Stefan Svenson, Andrzej Pawlowski, Philip D Marsh. Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis. Tuberculosis 2005 85, 29-38
Ann Williams, Brian W. James, Joanna Bacon, Kim A. Hatch, Graham J. Hatch, Graham A. Hall and Philip D. Marsh. An assay to compare the infectivity of Mycobacterium tuberculosis isolates based on aerosol infection of guinea pigs and assessment of bacteriology. Tuberculosis 2005; 85, 177-84
Williams A, Goonetilleke NP, McShane H, Clark SO, Hatch GJ, Gilbert SC, Hill AVS. Boosting with Poxviruses Enhances Mycobacterium bovis BCG Efficacy against Tuberculosis in Guinea-Pigs. 2005 Infection and Immunity, 73, 3814-3816.
Julia A. Tree, Ann Williams, Simon Clark , Graham Hall, Philip D. Marsh and Juraj Ivanyi. Intranasal BCG vaccine dosage needs balancing between protection and lung pathology.2004 Clin Exp Immunol. 138 405-409
Priscille Brodin, Laleh Majlessi, Roland Brosch, Debbie Smith, Gregory Bancroft, Simon Clark, Ann Williams, Claude Leclerc and Stewart T. Cole Enhanced protection against extrapulmonary tuberculosis with an attenuated live Mycobacterium microti vaccine inducing T-cell immunity against RD1 antigens. 2004. Journal of Infectious Diseases, 190:115-22
Anja W. Olsen, Ann Williams, Limei M. Okkels, Graham Hatch and Peter Andersen Evaluation of a Tuberculosis subunit vaccine based on a fusion of Ag85B and ESAT-6 in the aerosol guinea pig model. 2004. Infection and Immunity, 72:6148-50.
Joanna Bacon, Brian W. James, Lorenz Wernisch, Ann Williams, Kim A. Morley, Graham J. Hatch, Joseph A. Mangan, Jason Hinds, Neil G. Stoker, Philip D. Butcher, Philip D. Marsh. 2004.. The influence of reduced oxygen availability on pathogenicity and gene expression in Mycobacterium tuberculosis. Tuberculosis. 84:205-17
A.Williams, R. Reljic, I. Naylor, S. O. Clark , G. Falero-diaz, M. Singh, S. Challacombe, P. D. Marsh and J. Ivanyi (2004) Passive protection with IgA antibodies against tuberculous early infection of the lungs. Immunology, 111 328-333.
Mark A. Chambers, R. Glyn Hewinson, Ann Williams, Graham Hatch, Graham Hall, Philip D. Marsh, Dolores Gavier-Widen, D. Craig Wright, Joan Brisker. 2004. A single dose of killed Mycobacterium bovis BCG in a novel class of adjuvant (NovasomeTM) protects guinea pigs against lethal tuberculosis. Vaccine, 22;1063-1071
Hamasur B, Haile M, Pawlowski A, Schroder U, Williams A, Hatch G, Hall G, Marsh P, Kallenius G, Svenson SB Mycobacterium tuberculosis arabinomannan-protein conjugates protect against tuberculosis.Vaccine. 2003;21:4081-93.
Pym AS, Brodin P, Majlessi L, Brosch R, Demangel C, Williams A, Griffiths KE, Marchal G, Leclerc C, Cole ST Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nat Med. 2003;9(5):533-9
Dieli F, Ivanyi J, Marsh P, Williams A, Naylor I, Sireci G, Caccamo N, Di Sano C, Salerno A Characterization of lung gamma delta T cells following intranasal infection with Mycobacterium bovis bacillus Calmette-Guerin. : J Immunol. 2003;170:463-9
M A. Chambers, A Williams, G Hatch, D Gavier-Widén, G Hall, K Huygen, D Lowrie, PD. Marsh, & RG Hewinson Vaccination of guinea pigs with DNA encoding the mycobacterial antigen MPB83 influences pulmonary pathology but not haematogenous spread following aerogenic infection with Mycobacterium bovis : Infect Immun. 2002;70:2159-65
MA Chambers A Williams D Gavier-Widen A. Whelan, Lever MS, GA Hall, PD Marsh and R G Hewinson (2001). A guinea pig model of low-dose M. bovis aerogenic infection suitable for virulence, vaccination and immunological studies. Veterinary Microbiology 80: 213-226
Williams A, Davies AC, Marsh PD, Chambers MA, Hewinson RG (2000) Evaluation of the protective efficacy of Bacille Calmette-Guerin vaccination against aerosol challenge by M. tuberculosis and M. bovis. Clinical Infectious Diseases 30 (Suppl 3): S299-301
Lever MS, Williams A and Hall GA. 1995. Experimental transmission of Mycobacterium tuberculosis via the respiratory route. Supplement to the Journal of Applied Bacteriology 79 (1) pxiii.
Leach SA, Williams A, Davies AC, Wilson J, Marsh PD, Humphrey TJ Aerosol route enhances the contamination of intact eggs and muscle of experimentally infected laying hens by Salmonella typhimurium DT104. FEMS Microbiol Lett 1999;171:203-7
Williams A, Davies AC, Wilson J, Marsh PD, Leach S, Humphrey TJ. Contamination of the contents of intact eggs by Salmonella typhimurium DT104. Vet Rec 1998;143:562-3.
Humphrey TJ, Williams A, McAlpine K, Jorgensen F, O'Byrne C Pathogenicity in isolates of Salmonella enterica serotype Enteritidis PT4 which differ in RpoS expression: effects of growth phase and low temperature. Epidemiol Infect 1998;121:295-301
Lever MS, Williams A Cross-infection of chicks by airborne transmission of Salmonella enteritidis PT4. Lett Appl Microbiol 1996;23:347-9
Humphrey TJ, Williams A, McAlpine K, Lever MS, Guard-Petter J, Cox JM. Isolates of Salmonella enterica Enteritidis PT4 with enhanced heat and acid tolerance are more virulent in mice and more invasive in chickens. Epidemiol Infect 1996;117:79-88
Williams A, McBride BW, Hall G, Fitzgeorge RB, Farrar GH Experimental Legionnaires' disease in SCID-Beige mice reconstituted with human leucocytes. J Med Microbiol. 1995;42:433-41.
Williams A, Lever MS Characterisation of Legionella pneumophila antigen in urine of guinea pigs and humans with Legionnaires' disease. J Infect 1995 ;30:13-6
Williams, A., Rechnitzer, C., Lever, M.S., & Fitzgeorge, R.B. (1993). Intracellular production of Legionella pneumophila tisue destructive protease in alveolar macrophages. In: Legionella, current status and emerging perspectives. pp 88-90. Edited by: Barbaree, J.M., Breiman, R.F., & Dufour, A.P. Washington, D.C. American Society for Microbiology.
Rechnitzer C, Williams A, Wright JB, Dowsett AB, Milman N, Fitzgeorge RB Demonstration of the intracellular production of tissue-destructive protease by Legionella pneumophila multiplying within guinea-pig and human alveolar macrophages J Gen Microbiol 1992;138:1671-7
Tully M, Williams A, Fitzgeorge RB Transposon mutagenesis in Legionella pneumophila. II.--Mutants exhibiting impaired intracellular growth within cultured macrophages and reduced virulence in vivo. Res Microbiol 1992;143:481-8
Baskerville A, Fitzgeorge RB, Gilmour MI, Dowsett AB, Williams A, Featherstone AS. Effects of inhaled titanium dioxide dust on the lung and on the course of experimental Legionnaires' disease. Br J Exp Pathol 1988;69:781-92
Conlan JW, Williams A, Ashworth LA .Inactivation of human alpha-1-antitrypsin by a tissue-destructive protease of Legionella pneumophila.
Williams A, Featherstone AS. The early diagnosis of legionnaires' disease in a Legionella pneumophila aerosol-infected guinea pig model; comparison of a method developed for detecting Legionella pneumophila antigens in urine and the demonstration of circulating antibody by enzyme-linked immunosorbent assay. J Infect 1988;16:47-54
Conlan JW, Williams A, Ashworth LA In vivo production of a tissue-destructive protease by Legionella pneumophila in the lungs of experimentally infected guinea-pigs. J Gen Microbiol 1988;134:143-9
Williams A, Baskerville A, Dowsett AB, Conlan JW Immunocytochemical demonstration of the association between Legionella pneumophila, its tissue-destructive protease, and pulmonary lesions in experimental legionnaires' disease. J Pathol 1987;153:257-64
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