Current issues with meningococcal vacine programmes in the Netherlands

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Fiona van der Kliss' presentation at the 2013 Meningitis Research Foundation conference Meningitis & Septicaemia in Children & Adults

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Current issues with meningococcal vacine programmes in the Netherlands

  1. 1. Adolescent booster after single primary MenCC vaccination at young age: the TIM-study Fiona van der Klis 1 6 november 2013 RIVM-CIB
  2. 2. Introduction MenC conjugate vaccine in the Netherlands ● Implemented in Dutch NIP since september 2002 – Single vaccination for all children at 14 months of age – Vaccination coverage >95% ● Catch-up campaign 1-18 year olds in June-November 2002 – Vaccine uptake: 94% ● Vaccine: NeisVac, MenCC-TT 2 RIVM-CIB
  3. 3. Meningococci incidence since 1993 Source: NRBM, AMC/RIVM 3 RIVM-CIB
  4. 4. PIENTER studies ● PIENTER: nation-wide, cross-sectional, serosurveillance studies to monitor immune status of the Dutch population ● Allows to investigate the effect of the MenCC-vaccine immunity pre- and post implementation 95 96 97 Serum bank n=8539 98 99 00 01 02 03 04 05 Start MenC immunization Catch-up campaign <19 years 4 RIVM-CIB 06 07 08 Serum bank n=6377
  5. 5. MenC PS IgG GMCs pre- vs post-immunization MenC-specific IgG GMC (μg/ml) Pre-immunization era (n=2305) Post-immunization era (n=6376) Post-immunization era (n=6376) 3.5 3.5 3 3 2.5 2.5 2 2 1.5 1.5 1 1 0.5 0.5 70--79 60--69 50--59 40--49 31--39 25--30 23--25 21--22 19--20 17--18 15--16 13--14 11--12 9--10 7--8 6 5 4 3 2 15-24 mo 8-14 mo 0-7 mo 0 0 Age at bloodsampling 5 RIVM-CIB De Voer et al, PloS ONE, 2010, 5(8), e12144
  6. 6. MenC PS IgG prediction 2013 in NS 6 RIVM-CIB
  7. 7. Approaches ● Shift in schedule – Move dose from first year to second year of life – Recommend dose at later age, adolecence  3+1, 2+1, 1+1, 1+1+1 – The dutch situation  7 1
  8. 8. TIM-study Tweede Immunisatie MenCC studie = Second Immunisation MenCC 8 RIVM-CIB
  9. 9. Set-up TIM study ● 3 age groups (No interference with other vaccinations) – 10 years – 12 years – 15 years ● Vaccination with NeisVac-CTM at T0 – blood and saliva collection ● Follow-up 1 month (T1) and 1 year (T2) – blood and saliva collection ● Start: October 2011 – 9 years after introduction of MenCC vaccination into Dutch NIP 9 RIVM-CIB
  10. 10. Objectives ● Primary – Difference in serum bactericidal antibody titers and percentages above correlate of protection ● Secundary – MenC PS specific IgG and IgA in serum and saliva › Quantity › Subclass distribution › Avidity – Longitudinal kinetics of B- and T- cell memory immune responses – Effect on IgG antibody levels against tetanus – Antibody persistence 9 years after primary vaccination 10 RIVM-CIB
  11. 11. Methods ● Measurement MenC-PS specific IgG, IgG subclass and avidity levels: Fluorescent bead-based multiplex immunoassay ● Measurement functional antibody levels (SBA): – Baby rabbit complement – Meningococcal serogroup C strain C11 11 RIVM-CIB
  12. 12. 4667 approached Flow chart enrollment 705 responses 56 dropped out during inclusion procedure: 224 ‘no’ 481 assessed for eligibility - 40 ‘no’ after receiving additional information - 16 fear for venapuncture 268 ENROLLED 157 excluded: - 83 study fully enrolled - 31 medical history 12 year olds 15 year olds N=91 N=91 N=86 N=90 N=85 2 dropped out 1 no show 1 no show 1 no blood 1 ‘no’blood N=85 N=89 N=83 2 dropped out - 14 not available during study period 10 year olds N=88 - 21 immunisation history different 2 dropped out 3 dropped out T0 - 8 other reason 2 no blood 12 RIVM-CIB T1 T2
  13. 13. Baseline characteristics 10 year olds 12 year olds 15 year olds 91 91 86 53 (58) 44 (48) 41 (48) 1.2 (0.2) 2.7 (0.3) 5.8 (0.4) No. of priming doses of MenCC vaccine 1 1 1 Mean age at enrollment T0: years ( SD) 9.9 (0.3) 12.0 (0.3) 15.0 (0.3) Interval since primary MenCC vaccine: years ( SD) 8.8 (0.3) 9.3 (0.1) 9.2 (0.2) No. of enrolled participants Female: No. (%) Mean age at MenCC vaccine priming: years ( SD) 13 RIVM-CIB
  14. 14. Difference in SBA GMTs ** ** * MenC specific SBA GMT 100,000 10,000 T0 1,000 T1 100 T2 10 01 10 12 15 Age (years) * = P<0.01 ** = P<0.001 Stoof et al, in preparation 14 RIVM-CIB
  15. 15. SBA titers≥ correlate of protection 10 years T0 Total SBA ≥8: n (%) T1 Total SBA ≥128: n (%) T2 Total SBA ≥128: n (%) 12 years 15 years 91 91 86 17 (19)*‡ 31 (34)* 39 (45)‡ 88 90 85 85 (100) 89 (100) 85 (100) 85 89 83 81 (100) 87 (100) 80 (100) * 10 vs. 12 years P=0.02 ‡ 10 vs. 15 years P<0.001 15 14-11-2013 RIVM-CIB
  16. 16. Difference in MenC-PS specific IgG GMCs ** MenC-PS specific GMC (µg/mL) 1000.00 ** ** 100.00 T0 T1 10.00 T2 1.00 0.10 10 * = P<0.05 ** = P<0.001 16 12 15 Age (years) Stoof et al, in preparation 14-11-2013 RIVM-CIB
  17. 17. MenC-PS specific IgG decrease between T1 and T2 T1 GMC IgG μg/ml (95%CI) T2 GMC IgG μg/mL (95%CI) % decrease median (IQR) 10 year olds 134 (117-153) 12 (10-14) 92 (85-94)*‡ 12 year olds 194 (168-222) 23 (19-28) 86 (81-92)*# 15 year olds 174 (147-206) 33 (28-40) 81 (69-86)‡# * 10 vs. 12 years: P<0.001 ‡ 10 vs. 15 years: P<0.001 # 12 vs. 15 years: P<0.001 17 14-11-2013 RIVM-CIB
  18. 18. Conclusions ● 9 years after the single MenCC vaccination, 45% of the 15 year-olds had protective antibody levels, versus 34% in the 12 year-olds and 19% in the 10 year-olds ● All age groups developed extremely high antibody levels 1 month after the study MenCC vaccination – 1 year after the booster vaccination 100% of the participants had protective antibody levels ● 1 year after the study vaccination the 15 year-olds remained the highest antibody levels and showed the lowest decay rate  potential age for vaccination 18 14-11-2013 RIVM-CIB
  19. 19. Discussion ● 15 years seems a good age for second MenCC vaccination based on these immunological data ● Another sample after 3-5 years to follow-up decrease (2014-2016) ● Role of the age at priming. Another booster study including same age groups with similar priming ages and with MenACWY tetravalent vaccine 19 14-11-2013 RIVM-CIB
  20. 20. Acknowledgements ● RIVM-CIb – Susanne Stoof – Debbie van Rooijen – Nelleke Bakker – Pieter van Gageldonk – Mirjam Knol – Guy Berbers ● All participants TIM-study and their parents! ● Baxter for vaccines ● WKZ-UMC Utrecht – Lieke Sanders – Tom Wolfs 20 RIVM-CIB
  21. 21. SBA seroprevalence pre- vs post-immunization in NS Pre-immunization era (95/96) Post-immunization era (06/07) 100 Prevalence SBA ≥ 8 (%) 90 80 70 60 50 40 30 20 10 70--79 60--69 50--59 40--49 31--39 25--30 22--25 19--21 17--18 15--16 13--14 11--12 9--10 7--8 5--6 3--4 2 15-24 mo 8-14 mo 0-7 mo 0 Age at bloodsampling 21 RIVM-CIB De Voer et al, PloS ONE, 2010, 5(8), e12144
  22. 22. SBA seroprevalence pre- vs post-immunization in NS Pre-immunization era (95/96) Post-immunization era (06/07) 100 Prevalence SBA ≥ 8 (%) 90 80 70 60 50 40 30 20 10 70--79 60--69 50--59 40--49 31--39 25--30 22--25 19--21 17--18 15--16 13--14 11--12 9--10 7--8 5--6 3--4 2 15-24 mo 8-14 mo 0-7 mo 0 Age at bloodsampling 22 RIVM-CIB De Voer et al, PloS ONE, 2010; 5(8), e12144

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