Serogroup B Meningococcal Disease
Conditions
Brief summary
In this study the investigators are testing 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 (septicaemia) and can affect all ages, but especially children, adolescents and young adults. The bug is classified into different groups based on its outer capsule (or shell), and this study will test a new vaccine to protect against group B meningococcus (MenB) disease, which is the most common type in the UK. Vaccines are given to prepare the immune system to fight an infection. Vaccines work by stimulating the immune system to produce specialised proteins (called antibodies) and white blood cells designed to kill the bug later in life if needed. Vaccines against other types of meningococcus have been developed and saved many lives. However MenB is different because its outer capsule does not stimulate the immune system very effectively. There is therefore no broadly effective vaccine against MenB disease.
Detailed description
The vaccine the investigators are testing in this study is known as MenPF-1, and uses two bacterial proteins called PorA and FetA. PorA works to move particles across the bacterial cell wall, and FetA is needed to bind to iron that the bacteria need in order to grow. These proteins are found on almost all meningococcal bugs so they are an excellent target for the immune system, and it is thought that they could be the key to developing a new vaccine against MenB disease. MenPF-1 is a type of vaccine known as an Outer Membrane Vesicle (OMV) vaccine. This means that it has been produced from 'blebs' of the meningococcal bug's outer membrane, released by the meningococcus both during natural infection and in the laboratory. These outer membrane vesicles contain the PorA and FetA proteins, so can be used to make vaccines. The techniques used to produce the OMVs to make MenPF-1 are the same as those used in other very similar safe and effective vaccines. The MenB strain that the investigators use naturally produces PorA protein, and has been genetically modified to produce increased amounts of FetA for the OMV vaccine. MenPF-1 contains: * Many proteins, but especially PorA and FetA * Aluminium, which is safe and commonly used in many vaccines to better activate the immune system * Sugar and water for injection It is worth noting that the vaccine product MenPF-1 is designed to work against MenB and, even if successful, would not protect against all forms of meningitis. Also, it is not a live vaccine and therefore cannot cause a meningitis infection.
Interventions
BIOLOGICALMenPF-1.
A new vaccine against meningococcal disease.
Sponsors
Wellcome Trust
Norwegian Institute of Public Health
University of Oxford
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Willing and able to give informed consent for participation in the study * Aged between 18 and 50 years * In good health as determined by medical history, physical examination and clinical judgment of the investigators * (Females) Willing to use effective contraception (such as the oral contraceptive pill, contraceptive implant or barrier methods) from one month prior and for the duration of the study * Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of diary cards * Willing to allow his or her General Practitioner and/or Consultant, if appropriate, to be notified of participation in the study * Confirmation from GP that they are aware of the inclusion and
Exclusion criteria
and are satisfied from their knowledge of the volunteer that they are suitable to enrol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To investigate safety and tolerability of 25 µg or 50 µg of the serogroup B meningococcal protein vaccine MenPF-1 | 20 weeks | This will be measured by the recording and assessment of the following local and systemic adverse events following administration of each vaccine dose: 1. Tenderness and pain at the injection site 2. Induration 3. Redness 4. Swelling 5. Headache 6. Malaise 7. Myalgia 8. Nausea and/or vomiting 9. Fever 10. Blood parameters 11. Any unsolicited symptom(s) not listed above |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity | 20 weeks | Immunological assays to study the immune responses to vaccines, including: 1. Serum bactericidal antibody (SBA) assay. 2. Antibody concentration against vaccine antigens. 3. Quantification of circulating vaccine-induced B-cells. 4. Quantification of vaccine-induced, antigen specific T-cell responses and associated cytokine production. 5. Serum opsonophagocytic activity. 6. Gene expression profile after immunization and DNA storage for investigation of the genetic associations with the immune response. |
Countries
United Kingdom
Outcome results
None listed