Advice for Consideration of Quadrivalent (A, C, Y, W135) Meningococcal Conjugate Vaccine, for use by Provinces and Territories

Immunization Strategies

The goals of immunization programs against IMD should be: i) to prevent the occurrence of outbreaks or epidemics, ii) to control outbreaks or epidemics if not prevented, iii) to prevent sporadic cases and iv) to prevent secondary cases among close contacts of IMD cases.

As presented in Table 1, vaccination against serogroup C meningococcal infections is included in the immunization schedules of all Canadian provinces and territories. For primary immunization, the most frequent recommendation is a single dose of type C conjugate meningococcal vaccine (C- CMV) at 12 months (in effect in New Brunswick, Newfoundland and Labrador, Nova Scotia, Prince Edward Island, Quebec, Ontario, Saskatchewan and Nunavut). Primary immunization with three early doses (2, 4 & 6 months) was recommended in Alberta, but this schedule has recently been changed to administer the third dose at 12 months. Two-dose calendars exist in British Columbia (2 & 12 months), in the Yukon (2 & 6 months) and in the Northwest Territories (2 & 4 months). Finally, a calendar offering a single dose at 12 months, with catch up in the 4th year of primary school in Manitoba, a strategy justified by the epidemiological situation in 2004. Catch-up vaccination with variable schedules exists in most jurisdictions. In Alberta and Quebec, mass immunization campaigns have made any catch-up vaccination unnecessary.

Table 1: Recommendations regarding immunization schedule against invasive serogroup C meningococcal disease in Canadian provinces and territories (PHAC 2007/12/28)

	Primary Immunization	Catch-up (1 dose)*
Provinces
Alberta	3 doses : 2, 4 & 12 months	A mass vaccination campaign was conducted in 2000-2002, targeting the population aged 2-24 years, and polysaccharide meningococcal vaccines were used. Thereafter, conjugate serogroup C vaccines were used for those younger than 2 years of age.
British Columbia	2 doses : 2 & 12 months	1 dose in grade 6
Manitoba	1 dose at 12 months	1 dose in Grade 4
New Brunswick	1 dose at 12 months	Grades 9 (Menactra™)
Newfoundland & Labrador	1 dose at 12 months	Grades 4, 9
Nova-Scotia	1 dose at 12 months	Grade 7 and between 14 & 16 years
Ontario	1 dose at 12 months	Grade 7 and between 15 and 19 years
Prince Edward Island	1 dose at 12 months	Grade 9 (Menactra™)
Quebec	1 dose at 12 months	A mass vaccination campaign was conducted in 2001, targeting the population aged between 2 months and 20 years, using mainly type C conjugate meningococcal vaccine.
Saskatchewan	1 dose at 12 months	Between 4 & 6 years, Grade 6
Territories
Northwest Territories	1 dose at 12 months	A mass vaccination campaign was conducted in 2004, targeting all individuals of school- going age with type C conjugate meningococcal vaccine. Catch-up until 5 years. Screening and catch-up grade 9
Nunavut	1 dose at 12 months	Between 14 and 16 years
Yukon	2 doses: 2 & 6 months	Grade 9 catch-up; post secondary students leaving school and/or not previously vaccinated.

* A monovalent serogroup C meningococcal conjugate vaccine is used for catch-up, excepted in Prince Edward Island and in New Brunswick where Men4-DT is used.

Men4-DT has not been licensed for use in infants less than 2 years of age, and in this age group the immune response is low, particularly for the C, Y and W135 antigens (Rennels et al., 2002). In Canada, the first increase in meningococcal infection occurs near the age of 1 year and is mainly caused by serogroup C (Figure 1). In addition, there are no provinces or territories that have systematic vaccination at 2 or 3 years of age. For all these reasons, Men4-DT should not be used for primary vaccination against serogroup C in young children. Instead, primary vaccination should be performed with a monovalent conjugate serogroup C vaccine using one dose at the age of 12 months, or eventually at a younger age, using one or two doses with a booster dose in the second year (De Wals et al., 2006).

The preferred indication for Men4-DT in Canada is for vaccination of adolescents at the age of 12 years, just before the increase in incidence of IMD that occurs at the age of 13 years. For adolescents not previously vaccinated, this would be a primary vaccination. For those previously vaccinated with C-MCV at a young age, this would be a booster dose for serogroup C and a primary vaccination for the serogroups A, Y and W135. Results of epidemiological studies in the United Kingdom and Spain indicate a progressive decrease in protection during the years following primary vaccination with a serogroup C conjugate vaccine, which is more pronounced if the primary vaccination occurred at a young age (Trotter et al., 2004; Larrauri et al., 2005). Modeling of the relative effectiveness of various vaccination schedules suggests that revaccination near the age of 12 years is useful when the decrease of protection from primary vaccination at a young age is equal to or greater than 3% per year (De Wals et al., 2006). For protection against serogroup C, addition of revaccination around 10 years after a primary vaccination could offer additional duration of protection. In fact, observed concentrations of bactericidal antibodies against serogroup C are 35 times higher one month after revaccination with Men4-DT than after primary vaccination (Pichichero et al., 2005; El Bashir et al., 2006).

Like the conjugate serogroup C vaccine, Men4-DT probably induces appearance of mucosal antibodies (Zhang et al., 2000; Zhang et al., 2002). Therefore, vaccination of an important proportion of adolescents could significantly reduce transmission of pathogenic strains in the entire population, as the prevalence of carriage of N. meningitidis is maximal in this age group (Cartwright, 1995). In the United Kingdom, following a mass immunization campaign using C-MCV (reaching 81% of the population aged 18 years and under), observed carriage of serogroup C was reduced from 4.5% to 1.5% in students 15 to 17 years of age (Maiden et al., 2002), while the incidence of serogroup C IMD decreased by 52% in the non-vaccinated fraction of the target population (Ramsay et al., 2003). No epidemiological data exist regarding herd immunity induced by a routine vaccination program when only one or two cohorts are vaccinated per year. Trotter and coworkers (2005) developed a dynamic simulation model of meningococcal infection and disease that predicts a maximal indirect effect when adolescents are immunized with conjugate meningococcal vaccine. This herd immunity effect could be quite significant following a revaccination against serogroup C and could prevent new outbreaks. Regarding the other serogroups, herd immunity would be induced by vaccination of adolescents with Men4-DT, but a group of susceptible individuals would remain in children and older adults.

In the event of licensure of a quadrivalent meningococcal conjugate vaccine for children under 2 years of age which demonstrates a non-inferior immune response to the serogroup C polysaccharide as compared with currently available monovalent C vaccines, the ideal strategy would shift to the exclusive use of the quadrivalent product both for the priming (using either one dose at 12 months, or one or two doses below one year followed by a booster dose in the second year) and for the booster adolescent dose (ideally at 12 years).