How does the Bexsero® vaccine work?


Posted by Joe Wanford on 24 May 2016

Joe Wanford, Outreach Developer at the Department of Genetics, University of Leicester explains how the MenB vaccine Bexsero works and why it will not cover 100% of circulating MenB strains.

Vaccines work by injecting harmless components (known as antigens) of harmful bacteria and viruses into the body. Antigens on their own cannot cause disease. Instead, they prepare the body to fight infection by helping the immune system recognise disease-causing bugs.

If the body has seen the antigen before, it can deal with infection far more quickly, killing the bacteria before it has a chance to do any damage.

Bexsero® is a new vaccine that protects against meningococcal B (MenB) disease, the leading cause of meningitis and septicaemia in the UK. It was introduced for use in babies as part of the infant immunisation programme in September 2015.

Typically, vaccines against the other types of meningitis have used as an antigen the bacteria’s capsule, which is a sugary layer surrounding the bug (the MenACWY vaccine for example). However it has not been as easy to develop a vaccine for MenB as its capsule resembles a molecule on the surface of developing human cells. If we took this approach with a MenB vaccine, our immune system would recognise the bug as one of our own cells and wouldn’t protect us.

For MenB then, we have had to test different antigens from the surface of the bug to see how the immune system will react. After lots of testing, four surface antigens were picked. These are:
  • PorA
  • NadA 
  • fHbp
  • NHBA
Further information on each of the four vaccine antigens can be found on the Bexsero® website.
To understand how well Bexsero® is working, we first need to understand a bit about the variety of different MenB antigens and how this affects the way our immune systems react. Each of the Bexsero® antigens can have slight differences in their shape. Antigens of these different shapes are grouped into ‘families’. For the vaccine to offer protection to an infecting MenB strain, at least one of the antigens in the vaccine must be in the same family as the matching antigen on the infecting bug. This way the immune system can easily recognise the harmful bacteria based on the antigen it has already seen from the vaccine.

In addition to the different families, there are also differences in the amount of antigen we can see on the MenB surface between strains. In some cases, even if the antigen on the bug is within the same family as the matching vaccine antigen, there may not be enough of it on the surface for the immune system to recognise. In some cases only one of the antigens on an infecting MenB strain may match with any of the four antigens in the vaccine. It may be possible for an immunised person to get meningococcal B disease if this antigen isn’t present in a high enough quantity to stimulate an immune response. This is not important with PorA, as this antigen is usually present in a high enough quantity or not at all.

Diagram 2 Potential reasons why cases may occur in vaccinated people

In what situation might the vaccine not work?

MenB is a constantly evolving bacterium and making a vaccine that protects against all strains is very difficult. The antigen families given in the Bexsero® vaccine are predicted to cover more strains of the disease than any other. Scientific tests have estimated that the vaccine will protect us against between 73-88% of MenB strains. Despite this, there is still a very small chance that we may be infected by MenB strains capable of escaping the vaccine and causing disease.

Following vaccination, it takes a little while for the body to recognise the antigens and develop immunity. If we are infected with MenB very soon after vaccination it is still possible that we may get the disease. After developing immunity in the first few weeks, for us to be protected, at least one of the antigens on the bacterium must be a match for at least one of the antigen families given in the vaccine. Finally, for which ever antigen that matches, there must be enough of it on the bacterium for the immune system to recognise.

This does not mean that we should be worried about the Bexsero® vaccine. This does however mean that despite vaccination we should remain vigilant of the symptoms of meningitis and contact our doctors if we experience them because the quicker MenB disease is treated, the better the outcome.

What is Meningitis Research Foundation (MRF) doing to help?

MRF are funding projects aimed at evaluating the effectiveness of Bexsero®.

Determining the molecular basis of vaccine failure by a new MenB vaccine

Researchers: Dr Chris Bayliss, Dr Julie Morrissey, Prof Helen Cooper, Prof Ray Borrow
Location: University of Leicester, Leicester, UK, Public Health England, Manchester, UK

This project aims to develop a test that measures how much fHbp is present on a particular meningococcal strain. It could be used to evaluate whether a strain that has caused disease has enough fHbp to be covered by the Bexsero vaccine.

Individual host-pathogen interactions at a molecular level

Researchers: Dr Mary Ramsay, Dr Shamez Ladhani, Prof Chris Tang, Prof Martin Maiden, Prof Ray Borrow
Location: Oxford University, Oxford, UK, Public Health England, Manchester, UK

In order to truly understand how humans interact with bacteria, we need to study the genetic blueprint of patients with meningococcal disease alongside the genetic blueprint of the bacteria that caused their illness. Researchers will use this information to create a single database that will become an invaluable resource for decades to come.

As the meningococcal B vaccine is introduced, the database will include any cases of MenB disease that occur in vaccinated children, allowing invaluable insight into how the vaccine works and exactly why it did not protect against disease in a given child.

This project makes use of MRF’s genome library which identified the harmful strain of MenW disease and led to all UK teenagers being vaccinated with MenACWY.

More about the project 

Learning from both research and clinical experience of vaccine usage will help us to protect the most people we can from meningococcal B disease and get all the closer to our goal of eradicating meningitis!

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