Evaluation of strategies to reduce meningococcal disease risk in patients with complement deficiencies.
Complement deficiency is a condition which affects how well a person’s immune system functions. People with complement deficiency are at 10,000 times greater risk of contracting meningococcal disease than people without the condition.
They are given daily antibiotics and regular vaccines to protect them from meningococcal disease. We do not know how many of these patients take penicillin regularly, or if penicillin prevents people carrying the meningococcal bacteria.
Currently, most cases of meningococcal disease in the UK are caused by meningococcal group B (MenB) bacteria. A new vaccine has been licensed for use in patients with complement deficiency to protect them from Men B disease. It is known to be effective in healthy people, however, we do not know how effective it will be for people at high risk of developing meningococcal disease.
What the research team did
Dr Hughes and his team have a number of aims. Firstly, they hope to test the success and acceptability of the MenB vaccine programme by looking at the immune responses and adverse effects following vaccination for people with complement deficiency.
Secondly, they will examine how long the protective immune response continues after vaccination for other meningococcal strains (A, C, W, and Y). Finally, they will look for the meningococcal bacteria in throat swabs to see if penicillin is effective in stopping people carrying the germ.
Dr Hughes’ work will help us understand how to improve protection for people at increased risk of meningococcal disease. It will examine how effective the new MenB vaccine is for patients with complement deficiency, and whether they are likely to experience adverse effects.
The team will also gain a better understanding of whether patients should be re-vaccinated against MenA, C, W, Y within four years and how the meningococcal germ is carried. With this new knowledge, doctors will be able to better advise and care for patients with complement deficiency.
Summary and impact of results
184 patients with complement deficiency (as a result of a medication called eculizumab) were given the Men B (Bexsero®) vaccine. The vaccine was welcomed by patients and doctors. However, eculizumab interferes with the test used to determine if an individual has made a satisfactory response to vaccination. This study has shown that eculizumab blocks the immune response created by the vaccine, meaning patients are still vulnerable to the infection and that the antibodies made after the vaccine cannot be measured in this test. To try and find out if there is a protective response which can be measured, an alternative blood test has been studied (the OPA). This test now needs to be evaluated in a bigger study to determine whether the vaccine can make high enough antibody levels to protect against Men B disease.
MenACYW vaccine responses
Historic meningococcal vaccination and blood test results from 113 patients were collected. The research team determined that the current one-dose schedule only protects 23% of recipients, whereas a higher proportion (52%) of patients are protected if a two-dose vaccine schedule is adopted. They demonstrated that vaccine responses weaken over time and that a booster dose may be required every three years to improve vaccine responses.
Meningococcal carriage results
Swabs from patients’ throats were checked to determine if they carried meningococcal bacteria. There was no evidence of this. However, swabs from various locations in the UK often did not reach the laboratory in time. It was also found that these patients did not take the penicillin to prevent them from carrying meningococcal bacteria in their throats. During the study, three patients developed serious meningococcal diseases, despite being vaccinated. This demonstrates that routine antibiotic prophylaxis is very important.
The research team proposes future work to:
- Determine the protective levels of antibodies following MenB vaccination in the OPA assay
- Continue to follow up patients with complement deficiency to see how long the responses following meningococcal vaccines persist and to further understand why some patients respond well to vaccination and others don’t
- Investigate whether meningococcal bacteria are carried in the throats of these patients by using more rigorous test