Back in 1992 when I went to medical school there were a couple of diseases that used to terrify me above all others. No, I wasn’t paranoid! My fear was based on the fact that certain bacterial infections seemed to strike without warning, were easy to miss, and would quickly kill the young children who acquired them. Epiglottitis caused by Haemophilus influenzae type B (Hib) was one, the other was meningococcal sepsis caused by Neisseria meningitidis.
It is estimated that Neisseria meningitidis causes approximately 500,000 case of invasive infection annually worldwide, with about 800 laboratory confirmed cases per year in the UK. Ten per cent of these patients have severe septic shock, whereas the others have meningitis. Up to 40% of patents have both meningitis and septic shock at the same time. Contrary to popular belief, meningitis due to Neisseria meningitidis is actually less likely to lead to death then Streptococcus pneumoniae, 7.5% of patients versus 15.3%.
There are different capsular groups of N. meningitidis, the most common of which are A, B, C, Y and W. Vaccines against all except B have been available for some time, and the MenC vaccine has been part of the childhood immunisation schedule in England and Wales since 1999.
The MenC vaccine has been highly successful in reducing infection due to this capsular type, from 815 cases in 1998 to 29 in 2013. The majority of cases in 2013 were in non-vaccinated adults, but even in this group the incidence was reduced by herd immunity by 90% (from 238 to 24 cases). Herd immunity occurs when the vaccine is able to reduce carriage of the bacterium in the population and therefore non-vaccinated people do not get exposed to the microorganism.
A vaccine against MenB has been a long time coming. The main problem has been in trying to overcome the poor immune response generated by experimental vaccines against MenB because the bacterium has similar surface molecules to some normal human cells and therefore the vaccines are unable to make the host immune system recognise these molecules as foreign. In some respects this is probably a good thing as a vaccine that triggers an autoimmune response against normal human cells would be disastrous!
So what is the new MenB vaccine?
The new MenB vaccine (4CMenB) is a combination of four vaccine components which are essential to the bacterium but do not cross react with human cells. If you really want to know what they are, here you go (NB you really don’t need to remember this!):
- Porin A (PorA) - an outer membrane protein which forms a channel in the bacterial cell membrane
- Factor H binding protein (fHbp) – a protein which is present in all invasive meningococci and allows the bacterium to survive in blood by binding complement factor H preventing the complement system activating
- Neisserial adhesion A (NadA) – a molecule that helps the meningococcus bind to the nasopharyngeal epithelium and therefore colonise the host’s nose or pharynx
- Neisserial heparin binding antigen (NHBA) – a molecule that binds heparin and helps the bacterium evade complement-mediated cell killing
N. meningitidis group B contains slight variants in the components much like variations in the ingredients to make cakes. In a cake recipe you could use white flour, self-raising flour or wholemeal flour (for the PorA) and brown sugar, white sugar or caster sugar (for the fHbp), with butter, margarine or oil (for the NadA) and chocolate, lemon or vanilla flavouring (for the NHBA) but any combination of these ingredients can be used to make a cake. In invasive N. meningitidis group B strains there are a number of variations of the components but all strains contain a variation of the 4 main types. The specific vaccine component types have been shown to be present in the vast majority of strains and therefore will provide immunity to the majority of invasive N. meningitidis group B strains. To understand the above gobbledygook you’ll need a good immunology book or a patient Immunologist to explain further.
Is the vaccine effective?
It may come as a surprise to know that there have not been any large scale trials of the effectiveness of the MenB vaccine in the UK, but this in fact is normal procedure for many vaccines. Because the infection itself is not common you would need to vaccinate an awful lot of people in order to see if the vaccine prevented the infection occurring. To give an idea of the numbers involved, you would need to vaccinate approximately 25,000 under 18 year olds to prevent 1 case and hope that one of those 25,000 would have developed the infection without the vaccine...and how would you detect that the person was protected? The numbers involved in such a study would be enormous. It would be a dreadful study to do! So, in order to assess the effectiveness of the MenB vaccine, the UK uses its excellent surveillance system to study the impact of the vaccine after it has been introduced; this is what happened to MenC and all of our other vaccines in the past. It is predicted that the MenB vaccine will prevent over 90% of N. meningitidis group B infections.
Is the vaccine safe?
There have been a number of studies done to assess the safety of the MenB vaccine. These studies involve giving the vaccine to healthy children along with their other normal childhood vaccines. The studies that have been done show that fever and local reactions are more common when MenB is combined with the other normal childhood immunisations than the normal vaccines on their own:
- Fever: 77% versus 45% (but medical attention was not required)
- Local pain: 87% versus 59%
- Erythema: 83% versus 71%
- Swelling: 47% versus 34%
Although reactions to the vaccine were more common when MenB was given with other normal childhood vaccinations, this was not a significant safety concern and the conclusion was that the vaccine is safe and can be given at the same time as the other childhood vaccinations for convenience.
So what next?
The vaccine (under the trade name Bexsero, Novartis Vaccines and Diagnostics Ltd) has been licensed and a price agreed with the manufacturer and therefore the MenB vaccine is set to be introduced into the UK from September 2015. The vaccine will be offered to babies at the standard intervals of 2, 4 and 12 months.
Only time will tell if the MenB vaccine is as successful as it is hoped and predicted to be. During my career I have seen MenC almost disappear, and Hib become a rarity, so to see this happen to MenB as well would be really great.