Principal areas of research Biography Research In 1974, he obtained a Research Career Development Award (1978-1983) to train in molecular biology in the laboratory of Hamilton Smith at Johns Hopkins in Baltimore. He used recombinant DNA technology to investigate the molecular basis of the virulence of H.influenzae and did pioneering work on the biosynthesis, transport and surface assembly of the type b capsular antigen (polyribose-ribitol phosphate), thereby providing a robust rationale for the development of the type b, polysaccharide capsule-based conjugate vaccines. In 1984, having moved to Oxford, he and his team carried out studies on the public health impact of H.influenzae type b (Hib) invasive disease in the UK and performed the definitive efficacy study of a Hib conjugate vaccine in UK children. His group then established a long-term prospective study to investigate the impact of Hib conjugate vaccines, including the occurrence of a number of true vaccine failures. In subsequent work, these studies have provided a rational basis for important changes to the UK infant routine immunisation programme. This research on Hib vaccines was the stimulus for the formation of the Oxford Vaccine Group (OVG), currently one of the biggest clinical trials units for research on children’s vaccines in Europe. OVG is currently directed by Dr. Andy Pollard. The track record of OVG in vaccine research in research helped to secure Oxford University’s successful bid (RM as Principal Applicant) for Joint Infrastructure Funding to build a new Centre for Clinical Vaccinology in Oxford, completed in 2002. Since 1988, his research in the Weatherall Institute of Molecular Medicine has focused on the genetics, structure and biology of lipopolysaccharide (LPS) biosynthesis in H.influenzae and N.meningitidis. Supported by MRC and Wellcome Trust Programme Grants), his group has identified the key role of neuraminic acid (sialylated LPS glycoforms) in the pathogenesis of H.influenzae otitis media and has established the candidacy of LPS (specifically the inner core saccharides) as a Group B meningococcal vaccine candidate. He was a key collaborator in the H.influenzae genome project (completed by The Institute of Genomic Research in 1995). His laboratory used the whole genome sequence data to identify and characterise the more than 30 genes required for biosynthesis of the LPS core structures. His group was one of three that collaborated to sequence and annotate the complete genome sequence of N.meningitidis Group B and to identify novel vaccine candidates that are now undergoing Phase 2 trials in humans. Over recent years, his Group has expanded understanding of the adaptive behaviour of bacterial pathogens. This stemmed from the recognition that repetitive DNA, located adjacent to genes of H.influenzae, is responsible for antigenic variation of many key virulence factors, a role that is modulated by genes of genome maintenance. The role of the pathogen diversity generated by these hypermutable sequences (called contingency loci) has major implications for the evolution of bacterial virulence and the problem of developing sustainable anti-infective strategies and vaccines that are not rendered redundant by escape variants. Key publications Booy R, Hodgson S, Carpenter L, Mayon-White RT, Slack MPE, Macfarlane JA, Haworth EA, Kiddle M, Shribman S, St Clair Roberts J and Moxon ER. Efficacy of the Haemophilus influenzae type b conjugate vaccine PRP-T. Lancet 344: 364-366, 1994 Bouchet V, Hood DW, Li JJ, Brisson JR, Randle GA, Martin A, Li Z, Goldstein R, Schweda EKH, Pelton SI, Richards JC, Moxon ER. Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media. PNAS 100:8898-9803, 2003 Pizza M, Scarlato V, Masignani V, et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287: 1816-1820, 2000 Moxon ER, Bayliss CD and Hood DW. Bacterial contingency loci: The role of simple sequence DNA repeats in bacterial adaptation. 2006. Annual Review of Genetics. 40. 307- 333. |
||
