MenPF-1. A new vaccine against meningococcal disease.

• Research type

  Research Study

• Full title

  A phase I, single centre, open-label dose-escalation study to assess the safety and immunogenicity of three doses of 25µg or 50 µg of meningococcal serogroup B outer membrane vesicle vaccine MenPF-1.

• IRAS ID

  98210

• Contact name

  Andrew J Pollard

• Sponsor organisation

  University of Oxford

• Eudract number

  2012-001046-17

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  Summary of Research

  Neisseria meningitidis is also known as meningococcus and is a type of bacteria. The bacterium expressing the serogroup B capsule (MenB) causes the majority of the 1200 cases of invasive meningococcal disease infection each year and is the leading infectious cause of death in childhood. It does so by infecting the lining of the brain (meningitis) or the bloodstream (septicaemia). Conjugate vaccines made by combining sugars (called polysaccharide) taken from the capsule of the meningococcus, together with protein, have produced highly effective vaccines that can be given in infancy to protect against the meningococcal groups A, C, Y and W135. However the serogroup B meningococcus is different in that the structure of the capsule appears similar to some of our own human cells, and so the immune system can fail to recognise MenB for what it is and doesn't make the same response after vaccination that has made conjugated vaccines so successful in providing protection against the other types of meningococcus. The search for comprehensive protection against meningococcal disease therefore necessarily focuses on another site for the immune system to recognise MenB called the subcapsular antigens (subcapsule proteins) and in particular ones called PorA and FetA. Outer Membrane Vesicle (OMV) vaccines with PorA can provide protective responses and were safe and effective in trials in Norway, Cuba and New Zealand. This is very good news, but their limitation was that each OMV vaccine was serosubtype-specific. In other words, they provided protection against meningococci with the same PorA protein but not meningococci with a different type of PorA. MenPF1 contains PorA and FetA in addition. Based on detailed epidemiological evidence showing nearly 80% of invasive MenB contain certain combinations of both PorA and FetA, MenPF1 can hope to provide a wider range of protection against many sero-subtypes of MenB that can cause disease.

  Summary of Results

  In this study we tested a new vaccine against Neisseria meningitidis , the leading infective cause of childhood death in the UK. This bug (also known as meningococcus) can infect the lining of the brain (meningitis) or the blood stream and can affect all ages, but especially children, adolescents and young adults. We tested how good the vaccine MenPF-1 was at stimulating antibodies in the immune system to protect against meningococci bacteria proteins PorA and FetA that are on the surface of MenB bacteria. Volunteers received three injections of either 25µg (low dose) or 50 µg (high dose) of the MenPF-1 vaccine and provided us with blood samples before and after vaccination to test how well the vaccine worked.
  Our results showed that the new MenPF-1 vaccine was safe to give in adults and volunteers reported mainly local side effects at the injection site that were self-limiting. Immunogenicity (a measure of the immune response to the vaccine) was measured in our labs by serum bactericidal assay (SBA). The SBA measures how well the antibodies in people’s blood kill the bacteria. The greater the amount of meningococci bacteria that are killed by the antibodies in the blood, the better the vaccine is at protecting against MenB disease.
  After 3 doses of the MenPF-1 vaccine, the percentage of volunteers with protective levels of SBA was 98% for the strain of the MenB bacteria used to create the vaccine. This meant that the vaccine was effective against this strain. To test the FetA antibody response separately, a strain of bacteria was created that did not contain PorA, therefore PorA antibodies made in response to the vaccine MenPF-1 would not be able to kill this strain, which was called FetAonPorAoff. We found that after three doses of MenPF-1 vaccine, blood from 77% of volunteers was able to kill this strain (FetAonPorAoff) compared with 51% of volunteers for the strain FetAoffPorAoff, a strain that does not contain FetA or PorA. Therefore, more bacteria were killed when the FetA was present in the bacteria compared with the strain that did not contain FetA. These findings demonstrate that the MenPF-1 vaccine was able to generate FetA and PorA antibodies that were able to kill meningococci.

• REC name

  South Central - Oxford A Research Ethics Committee

• REC reference

  12/SC/0306

• Date of REC Opinion

  18 Jul 2012

• REC opinion

  Further Information Favourable Opinion