A new MenB (meningococcal B) vaccine
In January 2013, the first ever wide-ranging MenB (meningococcal B meningitis and septicaemia) vaccine was licensed by the European Commission, which judged that the vaccine, called Bexsero® was safe and effective. Licensure meant that the vaccine was authorised for use and governments could choose to implement it. Read the statement
The Joint Committee on Vaccination and Immunisation (JCVI), which advises UK governments on vaccination, has not recommended routine use of the vaccine because of uncertainties about its cost effectiveness. However it is encouraging that in response to feedback from MRF and other stakeholders, the JCVI have decided to commission further analysis before making a final decision about its routine use. We are waiting to hear the JCVI’s conclusions from this further analysis towards the end of March 2014. Meanwhile the National Immunisation Advisory Committee (NIAC), which advises the Irish Government, continues to discuss whether to introduce it into the routine immunisation programme in Ireland.
Whilst deliberations over the routine use of the vaccine in the UK and Ireland continue, stocks of Bexsero® have been made available privately, which means that people who can pay for it will be able to get it. In the very near future, the vaccine will also be made available free of charge to people in the UK with medical conditions that increase their risk of the disease.
MRF wants to see the vaccine introduced into routine immunisation programmes so that it is free for all who need it, as that is the fairest and most effective way to combat this deadly illness.
Why do we need a MenB vaccine?
For decades, MenB has been the most common cause of bacterial meningitis in the UK and Ireland. Vaccines are the only way to prevent meningitis and have almost eliminated some other kinds of meningitis. Since the first meningitis vaccine was introduced against Hib meningitis in 1992, many kinds of meningitis have been reduced or have dwindled to a mere handful of cases, including Hib, MenC and pneumococcal. Thanks to meningitis vaccines, thousands of children are alive today who would otherwise have died from these deadly diseases. Developing a MenB vaccine has been much more difficult – until now, protection against MenB has been a distant possibility. Meanwhile, meningococcal meningitis and septicaemia remain the leading infectious cause of death for children under five in the UK.
How effective is this vaccine?
The effectiveness of a vaccine is determined by many things, including how strong an immune response it produces (its ‘immunogenicity’), and how widely it covers disease-causing strains circulating in the country. Results from the vaccine trials are very encouraging, showing that the vaccine triggers a strong immune response in infants, toddlers and adolescents [1-3]. Studies of circulating MenB strains looking at how well they match the vaccine have predicted that it will cover approximately 88% of MenB circulating in the UK , and 78% of MenB in Europe over all. The actual proportion of cases prevented will depend on other things too, including how widely the vaccine is offered and taken up, whether it prevents the bacteria from being carried and passed on as well as protecting from disease, how long protection lasts, and whether it works sufficiently well in all age groups.
Why hasn’t the JCVI recommended implementing this new vaccine for all children through the routine immunisation programme?
The JCVI must consider cost effectiveness when making recommendations on new vaccines. Based on a cost effectiveness analysis, the JCVI released an interim statement in July
, stating that routine immunisation of infants or toddlers was unlikely to be cost effective, but that under certain circumstances routine adolescent immunisation may be cost effective. This statement highlighted uncertainties around the vaccine’s effectiveness, its coverage and its impact on carriage and transmission of MenB bacteria.
The JCVI invited MRF and other stakeholders to respond to their interim statement. After considering the JCVI’s conclusions carefully, MRF submitted a detailed response (http://www.meningitis.org/news-media/our-response-to-the-jcvi-72756
, with a particular focus on how we believe they had underestimated the burden of disease and impact on people affected in their cost effectiveness analysis. We are encouraged that the JCVI has agreed to take on board new and recently published evidence that MRF and other stakeholders provided, commissioning further analyses so that the potential for the MenB vaccine can be thoroughly explored before making a final decision.
The most recent JCVI meeting minutes are available from: https://www.gov.uk/government/policy-advisory-groups/joint-committee-on-vaccination-and-immunisation.
Is anyone entitled to receive the new MenB vaccine free of charge on the NHS?
The JCVI have advised that the MenB vaccine should be made available free of charge to people with medical conditions that put them at high risk of getting meningococcal disease, including people with asplenia, splenic dysfunction or complement deficiency, including those on Eculizumab therapy (the same groups who are entitled to get MenACWY vaccine under current guidelines, see https://www.gov.uk/government/publications/meningococcal-the-green-book-chapter-22
). People with at risk conditions will be able to get the vaccine from their doctor in the very near future. The JCVI has also advised that the vaccine could be offered to laboratory workers who are at risk of occupational exposure to MenB bacteria. Additionally there are plans for Public Health England (PHE) to produce guidance on the use of the vaccine for close contacts of cases of MenB disease.
If everyone at risk will soon be able to get the vaccine on the NHS, why is it so important for it to be offered universally in the national immunisation programme?
Although medical conditons such as complement deficiency greatly increase a person’s risk of getting meningococcal disease, the vast majority of people who get MenB infection have no risk factor. Many people who do have risk factors do not find out that they are at risk until after they get meningococcal disease. How can I get the vaccine?
GPs and travel clinics throughout the UK and Ireland have been informed that the vaccine is available. Start by asking your own GP for the vaccine, as if they can provide it, this is likely to be the least costly option. Some GPs may not be able to offer vaccines on private prescription but they may be able to arrange it via another surgery if they have an agreement. You can also get the vaccine from a travel vaccination clinic in your area, or a private GP practice. It is worth asking more than one clinic as prices can vary considerably.
Novartis has a customer service line in the UK for healthcare professionals only. GPs or other health professionals can ring to get the vaccine: 08457 451500, Mon-Thu 8am-4.45pm and Fri 8am-1pm. Novartis is prohibited by law from speaking to members of the public on this line, so can only suggest that they speak to their healthcare practitioner. In Ireland, Bexsero is available to order through a company called Allphar Services based in Dublin. Health professionals can ring to get the vaccine on 014688456.
If the vaccine is for someone with a high risk condition in the UK, it should NOT have to be paid for. Official immunisation guidelines for GPs will very soon be updated to explain that MenB vaccination should be offered to people with risk factors. In Ireland NIAC are still deciding whether the vaccine will be made available to people with at risk conditions free of charge. A decision is expected in 2014.How much will the vaccine cost if I want to get it privately?
As a guideline, the NHS list price of the vaccine is £75 per dose. It is being supplied to pharmacies in Ireland at a similar price. GPs or clinics may also charge for administration. More than one dose of the vaccine is needed for sufficient protection – the total number depends on the age of the person being vaccinated:
- Children between 2-6 months of age need 4 doses.
- Children between 6 months and 2 years of age need 3 doses.
- Children over 2 and adults require 2 doses, but it has not yet been established whether a booster dose is needed to maintain protection in these age groups.
The vaccine is not licensed for children under 8 weeks old because there is not enough information about how well the vaccine works in this age group.
How should the vaccine be given?
The table below shows the required number of doses and the time
intervals between doses needed to provide full protection, as
recommended in the Summary of Product Characteristics
|Age Group||Primary dose series ||Interval ||Booster? |
| 2 – 5 months||3||No less than 1 month||Yes, at 12 - 23 months|
|Unvaccinated infants 6 - 11 months||2||No less than 2 month||Yes, at 12 - 23 months with an interval of at least 2 months after the last primary dose|
|Unvaccinated children, 12 - 23 months||2||No less than 2 month||Yes, between 12-23 months after the last primary dose |
|Children, 2 - 10 years||2||No less than 2 month||No need yet established|
|Those over 11 years||2||No less than 1 month||No need yet established|
Is the vaccine safe?
As with all drugs, vaccines can cause side effects. Vaccine side effects may include soreness/redness/swelling or hardness of skin at the injection site, fever, lack of appetite, muscle aches, irritability, sleepiness and rashes. Almost 8,000 people, including more than 5000 infants and toddlers, have had the new MenB vaccine during clinical trials[1-3, 6-8]. Results from these trials have shown that Bexsero® has a good safety profile.Can Bexsero® be given at the same time as other routine vaccines?
Yes, the side effects seen when Bexsero® is given with other vaccines in the routine childhood schedule are the same as those commonly seen with vaccines in general. This is also true when the vaccine is given at the same time as hepatitis B and varicella vaccines.
Fever is more common in babies when Bexsero® is given alongside other vaccines although taking paracetamol after getting vaccinated (or at the same time) reduces the likelihood and severity of fever without affecting the immune response to any of the vaccines.What are the active ingredients in the vaccine?
The active ingredients that equip our immune system to fight MenB bacteria include four main components of meningococcal bacteria. Three of them are proteins found on the surface of the bacteria:
- Factor H Binding Protein (fHbp)
- Neisseria Heparin Binding Antigen (NHBA)
- Neisserial Adhesin A (NadA)
These three components help meningococcal bacteria invade and survive within the human body. In vaccinated people, the immune system can recognise and ‘neutralise’ these components, so the bacteria cannot make them ill.
The final ingredient is the New Zealand MenB Vaccine (MenZB) derived from the New Zealand outbreak strain of MenB (strain NZ 98/254).
All of these components have been processed and inactivated and are not part of any living bacteria, but can still stimulate the immune system.Are there any safety reasons not to have the vaccine? What about allergies?
People who have previously had an anaphylactic reaction to any of the vaccine components should not get the vaccine. In addition to the active components already mentioned, the vaccine is composed of sodium hydroxide, histidine, sucrose and water.
Anaphylaxis to current vaccines is very rare and is estimated to occur in one in a million doses given, although a recent study found no reports of anaphylaxis following more than 5 million preschool and infant immunisations over an entire year in the UK and Ireland.
People with severe immune system problems cannot have live vaccines, but the new MenB vaccine is not live. Those with egg allergies may need to avoid some flu vaccines, but generally food allergies are not a reason to avoid vaccination. People often worry that eczema, asthma, epilepsy and a family history of reactions to vaccinations are a reason to avoid vaccinations, but this is not trueWhy has it been so difficult to develop a MenB vaccine?
Meningitis vaccines developed up to now have been made from a fragment of the bacterial sugar coat. When we are vaccinated our immune system learns to recognise and attack this sugar as a ‘foreign invader’ by producing antibodies which help us destroy bacteria if we come into contact with one with the same sugar coat. However, the sugar coat of MenB bacteria does not trigger an immune response, because it looks like developing human cells. This means that the immune system does not recognise it as a foreign invader, and this protects it from attack. So using the sugar coat just does not work for MenB vaccine development.
The search for a MenB vaccine has focused on other elements of the surface of MenB bacteria but it has been very difficult to find elements which are both ‘visible’ to the immune system and present in every MenB strain. Even elements that are usually present are extremely variable, so the immune response against a vaccine made from one kind of MenB may not be capable of killing all the different MenB strains. Have there been other MenB vaccines?
Vaccines covering just one strain of MenB have been used successfully in New Zealand and Cuba to control epidemics in those countries caused by particular MenB strains. Our research has helped to show that neither of these vaccines would cover the majority of MenB infection in the UK and the rest of Europe. This new MenB vaccine, produced by Novartis, is the first one designed to cover different strains of meningococcal B infection around the world.
Why isn’t the MenB vaccine expected to cover 100% of cases?
It is impossible to be certain about the precise extent of coverage. The MenB vaccine is based on four main protein components found on the bacterial surface across most of the hundreds of different MenB strains. However, the structure of each protein can vary a lot and some bugs have more of a particular protein on their surface than other bugs do. The antibodies we produce after we’ve been vaccinated may not be able to recognise a protein carried on the surface of an invading MenB bug if its structure is a bit different to the protein in the vaccine, or if there is not very much protein to latch onto. If our antibodies cannot attach to an invading bug, our immune system will be unable to destroy it.
However, in addition to these main four protein components, other ingredients that are part of the vaccine formulation may also produce immunity. This may add to the coverage predicted for the four main vaccine components.
- Gossger, N., et al., Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial. JAMA, 2012. 307(6): p. 573-82.
- Santolaya, M.E., et al., Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study. Lancet, 2012. 379(9816): p. 617-24.
- Findlow, J., et al., Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant Meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy. Clin Infect Dis, 2010. 51(10): p. 1127-37.
- Frosi G, et al., Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage. Vaccine, 2013. Epub ahead of print.
- Vogel, U., et al., Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment. Lancet Infect Dis, 2013. 13(5): p. 416-25.
- Vesikari T et al., Immunogenicity of an investigational, multicomponent, meningococcal serogroup b vaccine in healthy infants at 2, 4, and 6 months of age., in Presented at IPNC, Sept 11-16, 2010; Banff, Canada. Poster #180.
- Snape, M.D., et al., Immunogenicity of two investigational serogroup B meningococcal vaccines in the first year of life: a randomized comparative trial. Pediatr Infect Dis J, 2010. 29(11): p. e71-9.
- Prymula R et al., Catch-up vaccination of healthy toddlers with an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) - exploration of a two-dose schedule., in Presented at 29th ESPID Meeting, 7-11 June 2011; The Hague, The Netherlands.
- Bai, X., J. Findlow, and R. Borrow, Recombinant protein meningococcal serogroup B vaccine combined with outer membrane vesicles. Expert Opin Biol Ther, 2011. 11(7): p. 969-85.
- Bexsero® Summary of Product Characteristics (Meningococcal Group B Vaccine [rDNA, component, adsorbed]). 2013 [cited 2013 December]; Available from: http://ec.europa.eu/health/documents/community-register/2013/20130114125155/anx_125155_en.pdf.
- Erlewyn-Lajeunesse, M., et al., Anaphylaxis following single component measles and rubella immunisation. Arch Dis Child, 2008. 93(11): p. 974-5.
- Department of Health. Contraindications and special considerations:the green book, chapter 6. 2013 [cited 2013 November ]; Available from: https://www.gov.uk/government/publications/contraindications-and-special-considerations-the-green-book-chapter-6.