Meningitis B (MenB), a virulent bacterium, causes the majority of cases of bacterial meningitis in the UK and Europe as well as elsewhere in the world including the US and Canada.
Fortunately, there is now an effective vaccine – Bexsero – which was licensed by the European Medicines Agency in 2013. Last year (2015), the UK government became the first in the world to announce a nationwide MenB vaccination programme. However, it is only available on the NHS for infants aged up to one year.
At the present time, an online petition to the UK Parliament calling for the vaccine programme to be extended to all children up to age 11 has reached nearly a million signatures. Images of dying children who have not been vaccinated against MenB have seared themselves into the public consciousness. Demand for the vaccine has proved so overwhelming that supplies are now limited and there are waiting lists for people who want to have the jab done privately.
I take a particular interest in the subject because I was one of the team that helped to develop Bexsero. We knew we had a huge task ahead of us. Other meningitis vaccines had already been developed in the 1980s, using a clever technology through which sugars, located on the bacterial surface of bacteria and called capsular polysaccharides, were bonded to protein. On their own, the polysaccharides did not protect infants, but when combined with protein, these conjugate vaccines produced a much more generous immune response which was also much longer lasting than that occurring by injection of the polysaccharide alone. These conjugates were the basis of several highly successful vaccines that induced protection against several forms of bacterial meningitis.
But this methodology didn’t work for MenB because conjugates of the MenB capsule and protein didn’t induce an immune response against the bacteria. In fact, there was a risk that they would trigger an autoimmune response, a reaction where the body’s own immune system turns on itself. This is because the MenB capsule mimics the sugars found on healthy human cells.
So a team from Chiron Vaccines and I decided to approach the problem at an entirely different angle – focus on the DNA of the bacterium and try and find antigens that would trigger the correct response. Fortunately we had the help of Craig Venter — a US scientist based at The Institute for Genome Research (TIGR) — who was a pioneer in the application of DNA sequencing methods. In 1995, Venter had published the complete genome sequence of the bacterium Haemophilus influenzae, opening up the possibility that this could also be done for other disease-causing bacteria, most importantly MenB.
Venter’s group and I started to sequence the genome of MenB in 1995 and in 1997, scientists from Chiron Vaccines (Siena, Italy), Rino Rappuoli and Mariagrazia Pizza, spearheaded a research consortium whose aim was to use the genome sequence to identify the proteins that over the next several years became the basis of the MenB vaccine, Bexsero. Starting with the MenB genome sequence, a large number of promising proteins,
candidate vaccine antigens, were tested to find those which would be most likely to protect against MenB disease. Eventually, this was reduced to a short list of 3 proteins. These now had to go through rigorous further testing to gauge their safety and confirm their capability to induce protective immunity in the laboratory before human clinical trials could be started. In 2004, Chiron Vaccines was acquired by Novartis. Testing of Bexsero in the clinic started in 2006. Altogether there were seven trials, involving more than 6000 children.
Now that Bexsero is available and has been successfully implemented (more than a million doses have been given in the UK alone), future research priorities include precise information on how many cases the vaccine prevents and whether the vaccine could also provide community protection (so-called ‘herd immunity’) to protect individuals who have not been vaccinated.
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- MenB – will Parliament cede to a million petitioners? - 21st March 2016