1. Vaccine against meningitis, current issues, what’s new & what are the future possibilities? Ray Borrow Professor of Vaccine Preventable Diseases, Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Royal Infirmary, Manchester, M13 9WZ, UK [email_address] 16 th June 2011

2. Advances in meningococcal serogroup B vaccines

3. The Independent (20p version) Friday 10 th June 2011

5. Laboratory confirmed cases of meningococcal disease, E&W, Five Weekly Moving Averages: 1997 - 2011 (week 13)

6. Percentage of capsular groups of laboratory confirmed cases of meningococcal disease, E & W, 1999 to 2011 (May 14 th )

7. Increase in serogroup Y disease in England & Wales, 2007 to 2009 Meningococcal Y Strain 2007 2008 2009 All cases Y:P1.5-1, 10-1 : F4-1: ST1655 (CC23) 3 3 15 21 Y:P1.5-1, 10-4 : F4-1: ST1655 (CC23) 0 1 5 6 Y:P1.5-1, 10-10 : F4-1: ST1655 (CC23) 1 0 1 2 Y:P1.5-1, 10-12 : F4-1: ST1655 (CC23) 0 0 1 1 Total 4 4 22 30

13. Immunogenicity of the Pfizer investigational MenB vaccine in adolescents (11 – 18 yrs) in 0, 2, 6 month schedule Richmond P, Marshall H et al. 17 th IPNC. Banff, Canada. September 11-16, 2010. VW04, page 37. A04 A05 B02 B03 LP2086 variant in SBA test strains % subjects with hSBA ≥ 4 Pre dose 1 1 month post dose 2 1 month post dose 3

16. Novartis 4CMenB Phase III study in infants % of subjects with hSBA ≥ 1:5 one month after dose 3 (2, 4, 6 month schedule) Vesikari T, Esposito S, Kimura A et al. Presented at the 17 th IPNC. Banff, Canada. September 11-16, 2010. P180, page 167. fHBP NadA PorA 1.4 Baseline Post-primary N = 1149 to 1152 % Subjects with bactericidal titers ≥1:5 Antigen NHBA

17. Findlow J, Borrow R, Snape MD et al. Clin Infect Dis 2010;51:1127-37. % Subjects with SBA titres ≥1:4 fHBP NadA PorA UK infant trial: proportion of subjects with hSBA titres ≥ 4 before & after Novartis 4CMenB vaccine Strains Baseline Post 3 rd dose Pre booster Post booster

18. Summary of systemic reactogenicity after receipt of Novartis 4CMenB vaccine Findlow J, Borrow R, Snape MD et al. Clin Infect Dis 2010;51:1127-37.

19. Potential coverage of the investigational 4CMenB vaccine against group B isolates from England and Wales

22. Clonal complex of MenB isolates from 2007/2008 N = 535

23. PorA genotype of MenB isolates from 2007/2008 N = 535

24. Cumulative percentage (from n=535) 20 36 50 58 62 64 67 68 70 71 Top ten PorA genotypes of MenB isolates from 2007/2008

27. Methodological issues- to determine expression and/or cross-reactivity? Antigen expression Cross-reactivity Combination of expression and cross-reactivity Mathematically calculated threshold of being killed by post-vaccination sera (i.e. being covered or not covered)

28. Meningococcal Antigen Typing System (MATS) Donnelly J et al. PNAS 2010;107:19490-19495

35. www.clinicaltrials.gov ClinicalTrials.gov Identifier: NCT01214850 A phase 3 to evaluate the effect of Novartis vaccine's 4CMenB and Menveo on pharyngeal carriage of N. meningitidis in young adults, n = 3,000. Group 1: Subjects in this arm will receive 2 doses of Novartis 4CMenB vaccine. Group 2: Subjects in this arm will receive one dose of Menveo. Group 3: Control arm-subjects in this arm will receive 2 doses of IXIARO (Japanese encephalitis). Sheffield, Manchester, Liverpool, Nottingham, Bristol, Middlesbrough, Oxford, Southampton, London

36. Pneumo

37. Incidence of Invasive pneumococcal disease per 100,000 population by age England & Wales 1998-2006

40. Vaccine efficacy estimates for each age cohort , 62 to 80+ years, are being determined. These new data will inform as to the pneumococcal vaccination of those 65 years+. The use of PPV23 in at risk groups also being looked in to. PPV23 (Pneumovax ™)

42. HPA Enhanced Surveillance of IPD Microbiology Labs in England and Wales Hospitals in England and Wales S pneumoniae Isolates sent for serotyping to RSIL Reports of S. pneumoniae isolates sent to CFI via CoSurv Electronic data imported into CFI systems Rapid telephone follow to get PCV vaccination status Clinical advice sent to GP and paediatrician sends blood to HPA Manchester DATA SHARED ON JOINT DATABASE AT CFI Antibody results HPA Manchester Feed back results with further advice

44. The impact on Invasive Pneumococcal Disease Children Under 5 yrs: Serotypes contained in PCV7

45. The impact on Invasive Pneumococcal Disease Children Under 5 yrs: Serotypes NOT contained in PCV7

46. The impact on Invasive Pneumococcal Disease Persons ≥ 5 yrs: Serotypes contained in PCV7

47. The impact on Invasive Pneumococcal Disease Persons ≥ 5 yrs: Serotypes NOT contained in PCV7

48. Incidence of invasive pneumococcal disease per 100,000 population by age England & Wales 1998-2010

49. Cumulative weekly number of reports of Invasive Pneumococcal Disease Serotypes in PCV 13 but not in PCV 7 Children aged <2 years in England and Wales by Epidemiological Year: