Independent report

Joint Committee on Vaccination and Immunisation (JCVI) interim statement on the immunisation schedule for children

Published 5 August 2022

Advice

The Joint Committee on Vaccination and Immunisation (JCVI) has been notified of the discontinuation of Menitorix© (Hib/MenC). This necessitates a change to the routine infant schedule as this vaccine is currently given at 12 months.

After careful consideration of the options, the JCVI advises that:

• an additional dose of Hib-containing multivalent vaccine should be offered at 12 or 18 months of ages – note that giving this at 18 months would require the creation of a new immunisation visit
• the second dose of measles, mumps and rubella (MMR) vaccine should be brought forwards from 3 years 4 months to 18 months of age to improve coverage
• based on the demonstrated decline of invasive meningococcal A, C, W and Y disease in the UK (primarily due to the success of the teenage MenACWY vaccination programme) and subsequent low number of cases to prevent, including a dose of MenC-containing vaccine (such as MenACWY) in the infant schedule is not recommended – efforts to sustain and improve coverage of MenACWY in adolescents are important to maintain herd immunity

Background

The Joint Committee on Vaccination and Immunisation is an expert scientific advisory committee that advises the UK government on vaccination and immunisation matters.

The JCVI has been notified that Menitorix© (Hib/MenC) will be discontinued. This was a commercial decision made by the marketing authorisation holder, GSK.

Menitorix© vaccine immunises against haemophilus influenzae type b (Hib) and invasive meningococcal group C (MenC) disease, and is currently given as part of the routine childhood immunisation schedule at 12 months of age. It is given alongside a dose of pneumococcal conjugate vaccine (PCV), MMR and meningococcal group B vaccine (4CMenB).

As Menitorix© is the only Hib/MenC combination product currently available on the UK market, changes to the routine infant schedule are necessary. It is estimated that, based on current UK stocks of Menitorix©, the current routine schedule can continue until 2025.

The JCVI discussed options for the necessary changes to the schedule in February 2020, June 2021, December 2021 and June 2022.

Haemophilus influenzae type b (Hib)

Menitorix© is the fourth dose of a Hib-containing vaccine given in the childhood immunisation schedule. The prior 3 doses are given as the hexavalent DTaP/IPV/Hib/HepB vaccine at 8, 12 and 16 weeks of age.

The introduction of routine Hib vaccination in 1992 led to a substantial reduction in Hib disease across all ages. However, in the early 2000s, a resurgence in Hib was observed associated with increased carriage in 1 to 3 year olds. While a catch-up programme was implemented to reduce the number of cases, the introduction of the accelerated infant schedule in 1990 (at 8, 12 and 16 weeks) was thought to be an important factor contributing to the increased incidence. As a result, a booster dose of Hib-containing vaccine at 12 months of age was introduced to the schedule in 2006. Since then, Hib has been under excellent control in the UK as a result of the current 3 + 1 schedule and sustained high coverage.

The JCVI considered numerous options including the use of single Hib-only containing vaccines to replace the Hib/MenC dose. Available supply of single Hib-only is unlikely to be sustainable in the longer term as it is not used elsewhere in Europe. An additional dose of a multivalent Hib-containing vaccine – such as the hexavalent ‘6 in 1’ (DTaP/IPV/Hib/HepB) or pentavalent (DTaP/IPV/Hib) – is likely to be a more appropriate choice for the longer term.

Rapid waning of antibody levels after primary immunisation indicated that infants were protected by population-level immunity and, therefore, delaying the Hib booster from the current offer of 12 months to 18 months could maintain disease control as long as high vaccine coverage is maintained. Hib control is more likely to be sustained longer term by the addition of a booster dose of Hib-containing vaccine in the second year of life (at either 12 or 18 months).

Meningococcal C (MenC)

The introduction of a MenC vaccination programme in 1999 with an extensive catch-up campaign up to 25 years of age led to a significant reduction in the number of cases of invasive meningococcal C disease.

Over time, there has been a reduction in the overall number of MenC-containing vaccine doses within the UK routine schedule. This reduction in doses is a direct result of the success of the programme in substantially reducing the number of cases of invasive disease due to herd immunity effects. The last remaining infant dose of single MenC vaccine was withdrawn from the routine schedule in 2016.

Currently, vaccination to protect against MenC is given at 12 months (Hib/MenC) and 14 years (MenACWY). The teenage MenACWY programme commenced in 2015 and has been successful in reducing incidence.

Alongside the teenage vaccination programme, the coronavirus (COVID-19) pandemic, and resulting implementation of social distancing and lockdown measures across the UK has led to further significant declines in the spread and detection of invasive meningococcal disease (IMD) (UKHSA 2022).

Due to the success of the teenage MenACWY programme and resulting indirect effects on reducing disease burden in infants, and the overall reduction in disease carriage due to the impact of the pandemic, the JCVI noted that direct protection in infancy may not need to be maintained, as a result of reduced transmission leading to herd immunity.

The committee considered that, if a dose of MenC-containing vaccine was still needed in the early childhood programme, then the MenACWY vaccine would be the preferred vaccine. This is to ensure long term-availability of vaccine and sustainability of any future programme.

The committee requested modelling data on whether vaccination against MenC was still required in the childhood schedule and, if so, at what age this should be given (at 3 months or at 12 months).

MenC and MenW protection is likely to be sustained indirectly from the teenage MenACWY programme if current levels of coverage are maintained, potentially eliminating the need for a primary dose. However, this relies on maintaining good uptake in the adolescent programme, which has been significantly impacted during the pandemic.

The incidence of IMD is higher in the first year of life compared with the second year of life. The JCVI reviewed modelling that evaluated the predicted impact of administering MenACWY at age 3 months and 12 months, as well as an adolescent programme, compared with only a dose of MenACWY in teenagers.

These findings suggested that indirect protection against MenC in infants is sustained as a result of the teenage MenACWY programme.

Over time, MenACWY carriage prevalence is expected to reduce to near elimination levels. This decline is attributable to the teenage MenACWY programme and is not observed in scenarios where there is no adolescent programme. A decline in transmission was accelerated by the effects of the pandemic and resulting reduction in social contact, despite the pandemic-related decrease in teenage MenACWY vaccine uptake. Near elimination levels are predicted to be reached by 2040 – earlier than previously expected.

Recent surveillance data support the declining incident in IMD caused by MenACWY strains in 2020 and this reduction has been maintained since pandemic restrictions have been lifted. It is expected that very few IMD cases caused by meningococcal groups A, C, W and Y will be observed by 2025 (when Hib/Men C supplies will be depleted), and therefore there are few cases that could be prevented by addition of a dose of MenACWY vaccine into the childhood schedule.

In addition, there is some cross-protection against meningococcal W disease from the 4CMenB vaccine (Bexsero). A recent paper (Ladhani and others) suggests that improving the timeliness of the 4CMenB vaccine could prevent more cases of meningococcal disease overall than adding a dose of MenACWY.

Maintaining good uptake in the teenage vaccination programme and catching up those who may have missed out during the pandemic is critical to ensure that the indirect protection is maintained. Modelling showed that the indirect protection is maintained even where there is a significant decrease in coverage – this was demonstrated by decreases seen due to COVID-19 pandemic disruption of the teenage programme. It is also essential that good surveillance of meningococcal infection and IMD is maintained to monitor the impact of the vaccination programme and expected overall decline of disease.

Due to the very few cases of IMD as a result of meningococcal A, C, W and Y strains predicted, it is very unlikely that an infant or toddler MenACWY immunisation campaign would be cost-effective.

Other considerations

An additional dose of multivalent Hib-containing vaccine also gives the opportunity to strengthen the protection against other infectious diseases covered by these vaccines, including polio, diphtheria and pertussis.

Since 2004, acellular pertussis vaccination has been used in the infant schedule and is known to provide less durable protection than the previous whole cellular pertussis vaccine. An additional dose of pertussis will augment the protection already offered by the routine programme, which is particularly relevant in light of the predicted heightened levels of pertussis transmission.

The committee discussed the option of removing another immunisation visit if adding the 18 months visit to maintain the same number of overall visits – however, the 8, 12 and 16-week vaccination model is trusted and considered to be successful. The introduction of the accelerated schedule in 1990 was as a result of aiming to improve pertussis control, and was demonstrated to increase coverage and provide earlier protection to infants from pertussis when risk of severe disease is highest. Removal of one of these visits, and therefore removal of a dose of pertussis-containing vaccine, may have implication on disease control in infants where risk of severe disease is highest.

The committee discussed the option to add an additional immunisation visit at 11, 13 or 18 months. On balance, 18 months was considered to be the best option as this allows space for the second dose of MMR vaccine to be brought earlier in the schedule from 3 years 4 months with the aim to increase coverage.

Studies in London (Lacy and others) where the second dose of MMR has been brought forward from 3 years 4 months to 18 months in response to measles outbreaks have shown that an earlier vaccination with the second dose of MMR is associated with significantly higher coverage at 5 years for this vaccine. Therefore, moving the second dose of MMR is a potential opportunity to increase coverage and provide increased protection against potential measles outbreaks.

Aside from Hib/Men C, currently a dose each of PCV, MMR and 4CMenB are also given at 12 months. Therefore, it may be preferable to give the multivalent Hib-containing vaccine at 18 months to reduce the number of vaccines given at one visit. This approach would also leave sufficient space in the programme to explore options for potential future vaccine programmes, such as varicella, which can either be given as a single or multivalent product. Maintaining the current scheduled visits would limit the options for this.

In terms of protection against polio, for population immunity it wouldn’t matter whether the additional dose of multivalent Hib (inactivated polio vaccine (IPV)-containing) vaccine was given at 12 or 18 months. Immunologically, a dose given later may be beneficial, particularly as maternal polio antibody (from the maternal pertussis vaccination programme) may still be present at 12 months. A dose at 12 months may offer earlier catch-up for any children who have missed prior doses of IPV-containing vaccine.

In the context of an additional DTaP and IPV-containing dose being given at 18 months and moving the second dose of MMR vaccine forwards, the JCVI considered the positioning of the pre-school booster (DTaP/IPV), which is given at 3 years 4 months.

The gap between pertussis-containing vaccines would be shortened as a result and there is evidence to suggest that frequent acellular pertussis booster doses leads to a shorter duration of protection from each subsequent dose. From an immunological perspective, moving this dose of pertussis-containing vaccine to later may be beneficial – however, this would leave a longer delay in those who may have missed previous doses. Positioning a vaccination visit prior to school also gives opportunity to catch up on any previously missed vaccine doses.

Any further consideration on timing of the ‘pre-school booster’ would need to be evaluated from an operational perspective.

References

Ladhani SN, Campbell H, Amin-Chowdhury Z and others. (2022) Timing of meningococcal vaccination with 4CMenB (Bexsero®) in children with invasive meningococcal group B (MenB) disease in England. Vaccine 2022: volume 40 (issue 10), pages 1493–1498.

Lacy J, Tessier E, Andrews N and others. Impact of an accelerated measles-mumps-rubella (MMR) vaccine schedule on vaccine coverage: an ecological study among London children, 2012–2018. Vaccine 2022: volume 40 (issue 3), pages 444–449.

Unpublished modelling data: estimating the potential number of cases prevented by infant or toddler immunisation with a MenACWY vaccine.

UK Health Security Agency (UKHSA). 2013. Haemophilus influenzae type b (Hib): the green book, chapter 16.

UKHSA. 2022. Meningococcal disease: laboratory-confirmed cases in England in 2021 to 2022.