Contents

12 Meningococcal disease

12.4 Vaccines

12.4.1 Introduction

Meningococcal vaccination programmes have been revolutionalised by the development of conjugate vaccines (firstly against group C but now also quadrivalent ACYW135 is available), which allow vaccination in younger children and are associated with the development of herd immunity when used widely (see section 1.2.3 for more information about conjugate vaccines). The inclusion of other serogroups (except serogroup B, which is not available in a conjugate vaccine) does not really offer much advantage in the New Zealand context, but those travelling to Africa, the Middle East and other areas with different serotype prevalence may benefit from broader protection.

Group B vaccines have been harder to develop because the group B capsule is poorly immunogenic and vaccines have been subtype specific. More recently, two recombinant group B vaccines have been developed, both of which cover a broad range of group B subtypes, but B group vaccines are not available in New Zealand at present.

The monovalent (C) and quadrivalent conjugate vaccines contain CRM197 or diphtheria or tetanus toxoid conjugate and are currently the only meningococcal vaccines available in New Zealand that can be effectively used in children aged under 2 years. Polysaccharide vaccines may still be useful and can offer three to five years’ protection in adults, but they are generally regarded as inferior to conjugate vaccines.

The meningococcal vaccines registered (approved for use) and available (marketed) in New Zealand are summarised in Table 12.4 below.

Table 12.4: Meningococcal vaccines registered and available in New Zealand

Name (manufacturer) Vaccine type
NeisVac-C
(Pfizer NZ Ltd)
Meningococcal group C conjugate
(MenCCV)
Menactra
(Sanofi-aventis NZ Ltd)
Quadrivalent meningococcal conjugate
(MCV4-D)
Nimenrix
(GSK)
Quadrivalent meningococcal conjugate
(MCV4-T)
Menomune ACYW-135
(Sanofi-aventis NZ Ltd)
Quadrivalent meningococcal polysaccharide
(4vMenPV)

Funded vaccines

No meningococcal vaccine is included on the routine Schedule, but in special circumstances, under the auspices of the medical officer of health and the Ministry of Health, meningococcal group C conjugate and quadrivalent meningococcal conjugate vaccines are recommended and funded (see section 12.5).

Two meningococcal conjugate vaccines are funded for certain at-risk groups.
  • Meningococcal group C conjugate vaccine MenCCV (NeisVac-C, Pfizer NZ Ltd) contains 10 µg of polysaccharide derived from the group C capsule, conjugated to 10–20 µg of tetanus toxoid. Other components include aluminium hydroxide and sodium chloride.
  • ​Quadrivalent meningococcal conjugate vaccine MCV4-D (Menactra, Sanofi-aventis NZ Ltd) contains 4 µg of each polysaccharide derived from the capsules of group A, C, Y and W135 N. meningitidis strains, each conjugated to diphtheria toxoid. Other components include sodium chloride and sodium phosphate.

Other vaccines

Group C vaccines

There are no other monovalent group C vaccines registered and available in New Zealand. 

Group A vaccines

There are no monovalent group A vaccines registered and available in New Zealand; group A strains are contained in the quadrivalent conjugate and polysaccharide vaccines.

Group B meningococcal vaccines

Group B vaccines are not currently registered in New Zealand. A strain-specific group B meningococcal vaccine (MeNZB, Chiron/Novartis) containing outer membrane vesicles (OMVs) derived from the epidemic strain B:4:P1.7b,4 (NZ 98/254) was developed for epidemic control in New Zealand and used between 2004 and 2008. The vaccination programme ceased in 2008 because of a decline in the incidence of group B disease. The immune response to the vaccine was shortlived and it is not expected that anyone previously vaccinated would still have existing immunity to B disease. This programme was covered in previous editions of the Handbook.

Since this time there have been major advances in group B vaccine development and there are now two recombinant group B vaccines (4CMenB and 2CMenB), both of which cover a broad range of group B subtypes. Neither vaccine is currently available in New Zealand.

The 4CMenB recombinant vaccine (Bexsero) contains four components from the group B bacteria: three different group B surface proteins plus detoxified OMV from the New Zealand group B epidemic strain. The 4CMenB vaccine has large-scale clinical trial data to support its use, and licensure has been granted in Europe, Australia, Canada and the US. The 4CMenB vaccine is associated with more local and febrile reactions than some other childhood vaccines. No serious adverse events have been identified, however, febrile seizures have occurred in temporal association with this vaccine.8

The 2CMenB recombinant vaccine (Trumenba) contains two group B surface proteins. One protein from each factor H binding protein subfamily (A and B) is included in the vaccine. The immunogenicity and safety of 2CMenB was assessed in individuals aged 10 years and older who received the vaccine in studies conducted in the US, Europe and Australia. The vaccine was licensed in the US in October 2014. The most commonly reported side effects by those who received the 2CMenB vaccine were pain at the injection site, fatigue, headache, joint pain and chills.9

In June 2015 the US Advisory Committee on Immunization Practices (ACIP) recommended that individuals aged 10 years or older at increased risk for meningococcal disease should receive meningococcal B vaccine (either 4CMenB or 2CMenB).9 In September 2015 England became the first country to introduce the 4CMenB vaccine as part of a funded schedule for infants.10 The vaccine is offered to infants at ages 2 and 4 months, with a booster at age 12 months. 

Quadrivalent meningococcal conjugate vaccines

​A second quadrivalent meningococcal conjugate vaccine MCV4-T (Nimenrix, GSK) is registered and available in New Zealand for individuals aged 12 months to 55 years. It contains 5 µg of each polysaccharide derived from the capsules of group A, C, Y and W135 N. meningitidis strains, conjugated to 44 µg of tetanus toxoid carrier protein. Other components include sodium chloride. 

Quadrivalent meningococcal polysaccharide vaccines

There is one quadrivalent meningococcal polysaccharide vaccine (4vMenPV) registered and available in New Zealand (Mencevax ACWY, GSK). It contains 50 µg of each polysaccharide derived from the capsules of group A, C, Y and W135 N. meningitidis strains.

Like other unconjugated polysaccharide vaccines, 4vMenPVs are less effective in children aged under 2 years and are approved for use only in children over this age.

12.4.2 Efficacy and effectivenessTop

Meningococcal group C conjugate vaccines

The first national immunisation programme using a conjugate group C meningococcal vaccine was introduced in the UK in 1999. Data from that programme indicates that a booster dose in the second year of life is important for sustained protection following infant vaccination. Some countries (eg, Australia) have introduced conjugate group C meningococcal vaccine as a single dose in the second year of life, with subsequent significant reductions in disease incidence.11

The conjugate vaccines containing tetanus toxoid (TT) as the carrier protein appear to be more immunogenic, with longer persistence of bactericidal antibodies.12, 13 Two studies showed that serum bactericidal titres at five years were higher in children whose primary vaccination used the TT conjugate.14, 15

Group C conjugate vaccine was introduced into the UK infant immunisation schedule at ages 2, 3 and 4 months, as well as via a mass vaccination campaign up to age 20 years. Four years after introduction the overall reported efficacy was at least 83 percent in children who had received the conjugate vaccine from age 5 months to 18 years.16 However, the vaccine offered little protection one year after the last dose in infants who were immunised only in the first six months of life.

Protective efficacy against carriage by adolescents of group C one year after the immunisation campaign was estimated at 69 percent.17 At the same time there was no increase in colonisation by the other meningococcal groups. Consistent with the reduction in meningococcal carriage rates, there has been a 67 percent reduction in group C disease among unvaccinated children within the target age groups and a reduction of 35 percent of cases in adults older than age 25 years, also unvaccinated.18 At the same time there is no evidence of capsular switching or an increase in disease caused by group B strains.19

The optimal vaccine schedule for sustained control of group C meningococcal disease by a universal programme has yet to be established. It is now recognised that circulating antibody is probably required for vaccine-induced protection and that antibody decay occurs quite rapidly in young children. Although conjugate vaccines can induce an anamnestic response, invasive disease develops within hours or days of acquisition and colonisation of the nasopharynx. This timeframe is shorter than that required for bactericidal antibodies to develop.

Herd protection, from reduced carriage resulting in reduced exposure to the organism, has an important role in the prevention of meningococcal disease. Consequently, further doses may be needed, possibly in early adolescence and then prior to leaving school. The exact timing will depend on any catch-up vaccination programme undertaken when the vaccine is first introduced, and the country’s specific epidemiology.

The optimal vaccine schedule in New Zealand (where we do not have a universal programme) is not known. In view of waning immunity, some experts recommend boosters every three to five years for individual protection.

Quadrivalent meningococcal conjugate vaccines

Immunisation against meningococcal disease with quadrivalent meningococcal conjugate vaccine is recommended in the US for all adolescents (at age 11 or 12 years and a booster at age 16 years). Individuals at high risk for meningococcal disease and underlying medical conditions may be given two doses, eight weeks apart, with boosters every five years if the risk condition persists (first booster given after three years if aged under 7 years at the time of the primary course).20

Because there is little group A meningococcal disease in New Zealand for the general population, there does not appear to be any major additional advantage over C conjugate vaccines, except for individuals travelling countries with different serotype predominance, such as Saudi Arabia (to the Hajj) or sub-Saharan Africa.

An early estimate of the effectiveness of the diphtheria conjugate quadrivalent meningococcal vaccine (MCV4-D, Menactra) among adolescents in the US was determined as 80–85 percent, which is similar to that reported for the polysaccharide vaccines.21  There was no published data for evidence of the effectiveness in older adults identified at the time of writing.

The MCV4-D vaccine was poorly immunogenic in infants aged under 6 months,22 and it is currently registered in New Zealand for children from 9 months of age.

The MCV4-T vaccine (Nimenrix) is registered in New Zealand for individuals aged 12 months to 55 years. Clinical trials showed that the vaccine was immunogenic in children above the age of 12 months, adolescents, and adults, and has an acceptable reactogenicity and safety profile.23 Other studies are now ongoing in order to determine the immunogenicity, reactogenicity, and safety of MCV4-T in infants from the age of 6 weeks.23

Quadrivalent meningococcal polysaccharide vaccines

Protective levels of antibody are usually achieved within seven to 10 days of vaccination with quadrivalent polysaccharide vaccines (4vMenPV).24 Immunity, as determined by antibody levels, lasts approximately three years, although in young children there may be a more rapid decline.

The effectiveness of 4vMenPV against disease due to group A or C N. meningitidis has been 85–100 percent in outbreaks involving children over the age of 2 years and adults. There is no similar efficacy data for protection against disease due to groups Y and W135.

In response to a meningococcal group C epidemic in Canada in the early 1990s, about 1.6 million doses of 4vMenPV were administered to people aged 6 months to 20 years. The overall field effectiveness of the vaccine was 79 percent (higher in teenagers and lower in children aged under 5 years).25 The epidemic waned both in provinces that vaccinated and in those that did not. A subsequent case-control study found a good level of protection (77 percent) was provided over a five-year period by a single dose of the polysaccharide vaccine in individuals aged 6 years and over, but in those aged 2 to 5 years only short-term protection was achieved.26

Revaccination with and hyporesponsiveness to polysaccharide vaccines

Revaccination with polysaccharide vaccines results in a reduced antibody response compared with the primary immunisation.27 In addition, following repeated vaccination with 4vMenPV, immunological hyporesponsiveness to the serogroup C component may be seen in both children and adults. This hyporesponsiveness can be partially overcome with meningococcal conjugate vaccines,20, 24 although additional doses of a conjugate vaccine may be required in young children.27 There is little response to the serogroup C component of the 4vMenPV before 18 months of age and little response to serogroup A before 3 months of age.27

12.4.3 Transport, storage and handlingTop

Transport meningococcal conjugate and polysaccharide vaccines according to the National Guidelines for Vaccine Storage and Distribution.28 Store at +2oC to +8oC. MCV4-D and MCV4-T should be protected from light. Do not freeze.

Reconstitution

MCV4-T (Nimenrix) and 4vMenPV (Mencevax ACWY) must be reconstituted with the supplied diluent and used as soon as possible.

12.4.4 Dosage and administrationTop

Meningococcal group C conjugate vaccine (MenCCV)

Each MenCCV dose is 0.5 mL, administered by intramuscular injection (see section 2.3). See Table 12.6 for a suggested meningococcal schedule for healthy children.

MenCCV can be administered concurrently with other scheduled vaccines, in separate syringes and at separate sites.29, 30

Quadrivalent meningococcal conjugate vaccines (MCV4)

Each MCV4 dose is 0.5 mL, administered by intramuscular injection (see section 2.3). See Table 12.6 for a suggested meningococcal schedule for healthy children.

Menactra (MCV4-D)

Menactra is registered in New Zealand for individuals aged 9 months to 55 years. For healthy children aged 9–23 months, two doses are given at least three months apart. For healthy individuals aged 2–55 years, one dose is given. See sections 4.2 and 4.3 for schedules for high-risk individuals. 

MCV4-D can be concurrently administered with other vaccines in separate syringes and at separate sites,31–34 except for PCV13. MCV4-D should be administered at least four weeks after PCV13. This is because when administered concurrently, there is impairment of the immune response to some of the pneumococcal serotypes.

Nimenrix (MCV4-T)

Nimenrix is registered in New Zealand for individuals aged 12 months to 55 years. One dose is given.

MCV4-T can be concurrently administered with other vaccines in separate syringes and at separate sites; however, there is no data on concurrent administration of MCV4-T and PCV13. 

Quadrivalent meningococcal polysaccharide vaccines (4vMenPV)

For those aged 2 years and older, a single dose of 0.5 mL is administered by subcutaneous injection (see section 2.3).