MenPF-1 - A New Vaccine Against Meningococcal Disease
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official 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|
- Safety [ Time Frame: 20 weeks ] [ Designated as safety issue: Yes ]
This will be measured by the recording and assessment of the following local and systemic adverse events following administration of each vaccine dose:
- Tenderness and pain at the injection site
- Nausea and/or vomiting
- Blood parameters
- Any unsolicited symptom(s) not listed above
- Immunogenicity [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Immunological assays to study the immune responses to vaccines, including:
- Serum bactericidal antibody (SBA) assay.
- Antibody concentration against vaccine antigens.
- Quantification of circulating vaccine-induced B-cells.
- Quantification of vaccine-induced, antigen specific T-cell responses and associated cytokine production.
- Serum opsonophagocytic activity.
- Gene expression profile after immunization and DNA storage for investigation of the genetic associations with the immune response.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Low dose vaccine arm
To investigate safety, tolerability and immunogenicity of 25 µg of the serogroup B meningococcal protein vaccine MenPF-1 in healthy adults aged 18 to 50 years of age when given three doses of vaccine with 8 weeks interval.
A new vaccine against meningococcal disease.
Experimental: High dose vaccine arm
To investigate safety, tolerability and immunogenicity of 50 µg of the serogroup B meningococcal protein vaccine MenPF-1 in healthy adults aged 18 to 50 years of age when given three doses of vaccine with 8 weeks interval.
A new vaccine against meningococcal disease.
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.
- 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.
|Centre for Clinical Vaccinology & Tropical Medicine (CCVTM)|
|Oxford, Oxfordshire, United Kingdom, OX3 7LE|
|Principal Investigator:||Andrew J Pollard, PhD||Oxford Vaccine Group|