Current issues with meningococcal vacine programmes in the Netherlands
-
Upload
meningitis-research-foundation -
Category
Health & Medicine
-
view
1.092 -
download
0
description
Transcript of Current issues with meningococcal vacine programmes in the Netherlands
Adolescent booster after single primary MenCC
vaccination at young age: the TIM-study
Fiona van der Klis
1RIVM-CIB6 november 2013
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
RIVM-CIB
Meningococci incidence since 1993
3
Source: NRBM, AMC/RIVM
RIVM-CIB
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
RIVM-CIB
95 02 07
Serum bankn=8539
Serum bankn=6377
Start MenC immunizationCatch-up campaign <19 years
96 97 98 99 00 01 03 04 05 06 08
5
MenC PS IgG GMCs pre- vs post-immunization
De Voer et al, PloS ONE, 2010, 5(8), e12144
0
0.5
1
1.5
2
2.5
3
3.5
0-7
mo
8-14
mo
15-2
4 m
o 2 3 4 5 6
7--8
9--1
0
11--1
2
13--1
4
15--1
6
17--1
8
19--2
0
21--2
2
23--2
5
25--3
0
31--3
9
40--4
9
50--5
9
60--6
9
70--7
9
Age at bloodsampling
Men
C-sp
ecifi
c Ig
G GM
C (μ
g/m
l)
Pre-immunization era (n=2305) Post-immunization era (n=6376)
0
0.5
1
1.5
2
2.5
3
3.5
0-7
mo
8-14
mo
15-2
4 m
o 2 3 4 5 6
7--8
9--1
0
11--1
2
13--1
4
15--1
6
17--1
8
19--2
0
21--2
2
23--2
5
25--3
0
31--3
9
40--4
9
50--5
9
60--6
9
70--7
9
Age at bloodsampling
Men
C-sp
ecifi
c Ig
G GM
C (μ
g/m
l)
Pre-immunization era (n=2305) Post-immunization era (n=6376)
RIVM-CIB
6
MenC PS IgG prediction 2013 in NS
RIVM-CIB
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
1
7
8
TIM-study
Tweede Immunisatie MenCC studie =Second Immunisation MenCC
RIVM-CIB
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
RIVM-CIB
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
RIVM-CIB
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
RIVM-CIB
12
Flow chart enrollment
56 dropped out during inclusion procedure:
- 40 ‘no’ after receiving additional information
- 16 fear for venapuncture
157 excluded:
- 83 study fully enrolled
- 31 medical history
- 21 immunisation history different
- 14 not available during study period
- 8 other reason
268 ENROLLED
10 year olds
N=91
12 year olds
N=91
15 year olds
N=86
4667 approached
705 responses 224 ‘no’
481 assessed for eligibility
T0
T1N=88
2 dropped out
1 no blood
N=90
1 no show
1 ‘no’blood
N=85
1 no show
N=89
2 dropped out
N=85
2 dropped out
2 no blood
N=83
3 dropped outT2
RIVM-CIB
13
Baseline characteristics
10 year
olds12 year
olds15 year
olds
No. of enrolled participants 91 91 86
Female: No. (%) 53 (58) 44 (48) 41 (48)
Mean age at MenCC vaccine priming: years (±SD) 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)
RIVM-CIB
Difference in SBA GMTs
14
10 12 1501
10
100
1,000
10,000
100,000
T0 T1
T2
Age (years)
Me
nC
sp
ec
ific
SB
A G
MT
***
* = P<0.01** = P<0.001
**
RIVM-CIB
Stoof et al, in preparation
SBA titers≥ correlate of protection
10 years 12 years 15 years
T0 Total 91 91 86
SBA ≥8: n (%) 17 (19)*‡ 31 (34)* 39 (45)‡
T1 Total 88 90 85
SBA ≥128: n (%) 85 (100) 89 (100) 85 (100)
T2 Total 85 89 83
SBA ≥128: n (%) 81 (100) 87 (100) 80 (100)
09-04-202315
* 10 vs. 12 years P=0.02‡ 10 vs. 15 years P<0.001
RIVM-CIB
Difference in MenC-PS specific IgG GMCs
09-04-202316
10 12 150.10
1.00
10.00
100.00
1000.00
T0
T1
T2
Age (years)
Me
nC
-PS
sp
ec
ific
GM
C (
µg
/mL
)
**
* = P<0.05** = P<0.001
**
**
RIVM-CIB
Stoof et al, in preparation
MenC-PS specific IgG decrease between T1 and T2
09-04-202317
T1GMC IgG μg/ml (95%CI)
T2GMC IgG μg/mL (95%CI)
% decreasemedian (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
RIVM-CIB
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
09-04-202318RIVM-CIB
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
09-04-202319RIVM-CIB
Acknowledgements● RIVM-CIb
– Susanne Stoof– Debbie van Rooijen– Nelleke Bakker– Pieter van Gageldonk– Mirjam Knol– Guy Berbers
● WKZ-UMC Utrecht– Lieke Sanders– Tom Wolfs
● All participants TIM-study and their parents!
● Baxter for vaccines
20RIVM-CIB
21
SBA seroprevalence pre- vs post-immunization in NS
0
10
20
30
40
50
60
70
80
90
100
0-7
mo
8-14
mo
15-2
4 m
o 2
3--4
5--6
7--8
9--1
0
11--
12
13--
14
15--
16
17--
18
19--
21
22--
25
25--
30
31--
39
40--
49
50--
59
60--
69
70--
79
Age at bloodsampling
Prev
alen
ce S
BA ≥
8 (%
)
Pre-immunization era (95/96) Post-immunization era (06/07)
De Voer et al, PloS ONE, 2010, 5(8), e12144RIVM-CIB
22
0
10
20
30
40
50
60
70
80
90
100
0-7
mo
8-14
mo
15-2
4 m
o 2
3--4
5--6
7--8
9--1
0
11--
12
13--
14
15--
16
17--
18
19--
21
22--
25
25--
30
31--
39
40--
49
50--
59
60--
69
70--
79
Age at bloodsampling
Prev
alen
ce S
BA ≥
8 (%
)
Pre-immunization era (95/96) Post-immunization era (06/07)
SBA seroprevalence pre- vs post-immunization in NS
De Voer et al, PloS ONE, 2010; 5(8), e12144RIVM-CIB