Routinely vaccinating adolescents against meningococcus: targeting transmission & disease

Figures & data

Figure 1. Simplified illustration of the pivotal role of adolescents in the epidemiology of meningococcal disease compared to other pathogens that also cause invasive disease [25,28,31,32,42,43].

The frequency of interactions between adolescents and other specific age groups may depend on factors including culture and social norms. This figure illustrates the potential of adolescents to transmit to all contacts, regardless of age. Grey arrows indicate transmission of pathogens.Image credit: Copyright: <a href = ‘http://www.123rf.com/profile_majivecka’>/123RF Stock Photo</a>; Image of woman: http://shutterstock.com/.

Figure 2. Evidence of herd protection in countries which implemented a large catch-up campaign (the Netherlands [44] and the United Kingdom [46]) after the onset of meningococcal serogroup C conjugate vaccination programs.

Vaccination commenced in the Netherlands in 2002: one dose administered at 14 months of age with catch-up to age 18 years, inclusive. Vaccination commenced in the U.K. in 1999: administered at 2, 3, and 4 months of age with catch-up to age 18 years, inclusive. For the U.K. 2014 data are provisional.

Table 1. Phase II and III studies of MenACWY conjugate vaccines and MenB vaccines in adolescents.

		Age			Serogroup
Author	Country	(years)	NCT	N	A	C	W	Y
ACWY-TT (Nimenrix, GSK Vaccines^a)					rSBA % ≥8
Phase II
Ostergaard [59]		15–19	NCT00126945	23–25	100 (83.9; 100)	100 (85.2; 100)	100 (85.2; 100)	100 (85.2; 100)
Bermal [60]	Philippines, India, Taiwan	11–17	NCT00464815	760	100 (99.5; 100)	100 (99.0; 100)	99.7 (99.1; 100)	99.9 (99.3; 100)
Phase III
Ostergaard [61]	Sweden, Denmark	11–17	NCT00465816	113	100 (96.8;100)	99.1 (95.3; 100)	100 (96.8; 100)	100 (96.8; 100)
				335^b	99.7 (98.4; 100)	99.7 (98.5; 99.9)	100 (99.0; 100)	99.7 (98.5; 100)
Lupisan [62]	Philippines, Thailand, Panama	18–25	NCT01154088	359–375 (lotA)	100 (99.0; 100)	100 (99.0; 100)	100 (99.0; 100)	100 (99.0; 100)
Bermal [60]	Philippines, India, Taiwan	11–17	NCT00464815	760	100 (99.5; 100)	99.7 (99.0; 100)	99.7 (99.1; 100)	99.9 (99.3; 100)
					hSBA % ≥8
Baxter [63]	U.S.	10–25	NCT00454909	479–517	81.9 (78.2; 85.1)	96.1 (94.0; 97.6)	91.4 (88.6; 93.8)	95.2 (92.9; 96.8)
ACWY-DT (Menactra, Sanofi Pasteur)
Jackson [64]	U.S.	11–18	NCT00450437	288–501	67 (62; 72)	84 (80; 87)	88 (84; 92)	69 (63; 74)
Baxter [63]	U.S.	10–25	NCT00454909	149–173	70.7 (63.1; 77.4)	98.8 (95.9; 99.9)	76.5 (68.9; 83.1)	81.8 (75.1; 87.3)
					hSBA % ≥4
Halperin [65]	U.S., Canada	10–25	NCT01165242	286–306	73.1	98.3	83.2	94.1
ACWY-CRM (Menveo, GSK Vaccines)					hSBA % ≥8
Phase II
Jackson [66]	U.S.	11–17	Not provided	148	81 (74; 87)	84 (77; 90)	91 (84; 95)	95 (90; 98)
Phase III
Jackson [64]	U.S.	11–18	NCT00450437	1024–1483	75 (73; 78)	84 (82; 86)	96 (95; 97)	88 (85; 90)
Phase II or II/III					hSBA≥ 4
4CMenB (Bexsero, GSK Vaccines)					44/76-SL^c	5/99^c	NZ98/254^c
Santolaya [67]	Chile	11–17	NCT00661713	98–126^d	100 (97–100)	100 (96–100)	100 (95–100)
				179–211^e	100 (97–100)	100 (97–100)	100 (97–100)
rLP2086 (Trumenba, Pfizer)					PMB1745^f	PMB17^f	PMB1321^f	PMB2948^f
Richmond [68]	Australia, Spain, Poland	11–19	NCT00808028	–	92.8	86.6	88.0	83.9
					PMB1256^f	PMB3302^f
					~75	100

N = number in the according-to-protocol cohort.

^aNimenrix is a trademark of GSK group of companies, licensed to Pfizer.

^bSubjects received ACWY-TT co-administered with Twinrix (combined hepatitis A and B vaccine, GSK Vaccines).

^cIndicator strains: i.e. strains selected because they express one of the MenB vaccines proteins.

Results after subjects received two doses at a 1-month^d or 2-month^e interval.

^fTest strains randomly selected from groups encompassing 1263 invasive MenB strains from several countries.

Table 2. Studies of nasopharyngeal carriage of meningococcus after meningococcal conjugate vaccination.

Country	Campaign/study	Age group	Population	Serogroup	Carriage prevalence (%)
					Study year	Study year
					1999 (N = 14,056)	2001 (N = 17,770)
U.K. [69]	1999 MenC campaign	2, 3, 4 months with catch-up to 18 years	Students (vaccinated)	All	16.7	18.7
				C	2.51	0.48 (p < 0.001)
Burkina Faso [72]	2010 MenA campaign	1–29 years	1–29 years (vaccinated)		2009 (N = 20,326)	2011 (N = 22,093)
				All	3.98	6.95
				A	0.39	0 (p < 0.05)
Chad [50]	2011 MenA campaign	1–29 years			2011 (N = 4278)	2012 (N = 5001)
			<1 (unvaccinated)	All^a	1	0
				A	1	0
			1–29 (vaccinated)	All^a	45	39
				A	25	1
			>30 (unvaccinated)	All^a	10	2
				A	6	0
					Group	Group
England [70]	Study in university students	18–24 years			MenACWY-CRM (N = 983)	Control^b (N = 984)
			2 months post-dose 1	CWY	6^c	7
				Y	5^c	7
Poland [71]	Study in professional soldiers	21–52 years	1–3 years post-MenACWY vaccine		MenACWY (N = 257)	Unvaccinated (N = 302)
				All	1.2	9.6
				B	0.8	2.3
				C	0	2.3
				Y	0	2.6
				Other	0.4	2.3

N = number studied.

^aAll = serogroups A, W, Y, and other.

^bReceived Japanese encephalitis vaccine.

^cStatistically significant difference compared with controls who received placebo.

Table 3. Routine meningococcal immunization strategies in use globally [74–77].

	Vaccines in use in routine immunization schedules			Age groups targeted for immunization
Country	MenC vaccines	MenACWY conjugate vaccines	MenB (protein/ OMV) vaccines	Infant	Toddler/child	Adolescent
Austria	Y	Y			12–14 months	12 years MenACWY
Belgium	Y				15 months
Cyprus	Y				12–13 months	At risk from 2 years MenACWY-PS
Czech Rep.		Y	Y (protein)	2, 3, 4 months MenB (+catch-up^a)	1–2 and 5–6 years MenACWY	13–15 years MenACWY
France	Y				12–23 months	2–24 years MenC
Germany	Y				11–23 months	2–17 years MenC
Greece	Y	Y		2, 4 months	6 months – 5 years	11 years MenACWY
Iceland	Y			6, 8 months
Ireland	Y			2, 4 months	13 months
Italy	Y		Y (protein: some regions)		13–15 months	11–18 years MenC
Liechtenstein	Y				12–15 months	11–15 years MenC
Luxembourg	Y				13 months
Netherlands	Y				14 months
Poland	Y			2–6 months	From 6 months
Portugal	Y				12 months
Spain	Y			2 months	12 months	12 years MenC
U.K.	Y	Y	Y	3 months (MenC) 2, 4 months (MenB from Sept 2015)	12–13 months (MenB & C)	14–15 years MenC (MenACWY from Aug 2015)
U.S.		Y				11–12 and 16 years
Canada	Y	Y			12 months	12 years
Australia	Y	Y			12 months
Argentina		Y		2, 4 months	12 months
Brazil	Y			3, 5 months	12–15 months
Cuba			Y (OMV)	3, 5 months
Chile		Y			12 months (MenACWY)

OMV: outer membrane vesicle vaccine. The Cuban vaccine (VA-MENGOC-BC) is a serogroup B OMV plus a serogroup C polysaccharide vaccine. MenACWY-PS: quadrivalent polysaccharide vaccine.

Targeted strategies of at-risk groups are not presented here.

^aCzech Republic, MenB 3 priming + booster doses in infancy, 2 doses in 6-month to 2-year-olds, 2 doses in 2- to 10-year-olds, 2 doses in 13- to 15-year-olds.

Table 4. Vaccination strategies targeting meningococcal disease.

Strategy	Advantages	Disadvantages
Infant vaccination	Early, direct protection of high incidence age group High coverage achievable if linked to other routine immunizations	Low immunogenicity and multiple doses needed Rapid waning of immunity Very young (unvaccinated/partially vaccinated) infants not covered High costs (2 + 1 schedule) Low impact on herd protection without catch-up
Toddler vaccination	Less doses needed Better immune response compared to infants Relatively early protection Lower costs High coverage achievable if linked to other routine immunizations	No direct protection of infants Low impact on herd protection without catch-up Rapid waning of immunity
Catch-up vaccination	Immediate and substantial achievement of herd protection Direct protection of vaccinated cohorts Protection of unvaccinated age groups	High cost in the beginning (budget impact) High coverage necessary for success (organizational challenge)
Adolescent vaccination	Direct protection of at-risk group Addressing age group with highest carriage High impact on herd protection Lower costs (less doses)	High coverage difficult to achieve

Table 5. Modeling results of meningococcal vaccine effectiveness under different schedules.

	U.S. [94]	U.S. [95]			Canada [96]			U.K. [93]
Model	Monte Carlo	Cohort simulation			Markov-like			Dynamic transmission
Incidence data	ABC, 1991–2002	ABC, 1993–2002			Canadian surveillance data for 1995–2001			Hospital episode statistics 2005–2012
Time frame	10 years	years			–			100 years
Reference	No vaccination	No vaccination			No vaccination			No vaccination
Vaccine efficacy (VE)	93% (78–98)	91.5% (65–98)	92% (65–98)	93% (78–98)	98.3% (96.5–100) at 1 year dose, 97.6 % (93.0–99.7) at 12 year dose			95%
Herd protection	Age-specific U.K. data	None	None	None	67% (52–77)			30% efficacy against carriage
Duration of protection	10 years	22 years (25% decrease in VE after 10 years)			Decrease in VE of 9.6% per year after toddler dose and 3.3%/1.7% per year after adolescent dose/booster			18 months after priming, 36 months after booster, 120 months in adolescents
Population	11- to17-year-olds	Birth cohort	Birth cohort	11-year-old cohort	Continuous population			Birth cohort
Schedule	11 years	2, 4, 6 months	12 months	11-year-olds	1 year	1 year + 12 years	1 year + 12 years	2, 3, 4, 12 months	2, 3, 4, 12 months + 13 years	13 years (+catch-up)
Catch-up	11–17 years	None	None	None	None	None	None	None	None	14–17 years
Vaccine	MenACWY	MenACWY	MenACWY	MenACWY	MCC	MCC/MCC	MCC/MenACWY	4CMenB	4CMenB	4CMenB
Coverage	70% (66–95)	77 % (34–90)	91% (54–98)	71% (16–95%)	90%	90%/70%	90%/70%	88% strain coverage. Age specific uptake
N (%) cases prevented
With herd protection	825 (48%) annually				1.6 (28%)	3.9 (68%)	4.8 (85%)	52,152 (26.3% in 5 years)	91,304 (48.8% in 10 years, 59.7% in 20 years)	64,667
Without herd protection	156 (9%) annually	447 (41%) over 22 years	385 (35%) over 22 years	270 (45%) over 22 years	1	1.7	2.0	–	–	–

ABC: Active Bacterial Core Surveillance; MCC: meningococcal serogroup C conjugate vaccine.

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