Multivalent Meningitis Vaccines
Meningococcal disease is a potentially fatal illness caused by the Neisseria meningitidis bacterium. Due to the difficulty in recognising the early signs of an infection, the best method of protection is vaccination.
Oxford researchers have successfully introduced difficult to isolate immunogenic peptides (PorA) into factor H binding protein (fHbp). These modified fHbp units allow presentation of the immunogenic PorA regions to the immune system and initiation of an immune response. This has potential in the development of single protein, multi-valent vaccines.
Neisseria meningitidis (meningococcus) is a bacterium that inhabits the upper respiratory tract of humans and is a major cause of disease. Worldwide there are approximately 500,000 cases of meningococcal disease each year and around 10 percent of these are fatal. The disease is a particular threat to children and can cause profound disability in survivors. Rapid disease progression and non-specific early symptoms mean that vaccination is the best way to protect against meningococcal infection. However, existing serogroup B vaccines have relatively low efficacy in infants and are complex, multi-component compositions that are expensive to make.
PorA – An integral outer membrane protein
PorA is an integral outer membrane protein and a major target of the immune response against meningococcal outer membrane vesicles. These factors make it an ideal vaccine candidate, however, PorA is difficult to produce in its native conformation due to the presence of large, membrane-spanning, hydrophobic regions, which prevent the recombinant protein from folding correctly. Current vaccines based on PorA are poorly defined and have limited efficacy.
Combine and conquer
Oxford researchers have introduced small regions of PorA into Meningococcal factor H binding protein (fHbp), a key antigen in vaccines being developed against serogroup B Neisseria meningitidis. The incorporation of PorA loops into the fHbp structure results in a chimeric molecule, which presents the appropriate regions of PorA to the immune system, eliciting the desired immune response. This methodology could be extended to a wide range of immunogenic integral outer membrane proteins.
The advantages of this technology include:
- Immunogenic regions of PorA can be isolated in the correct conformation
- fHbp scaffold is already a key antigen in other meningitis vaccines
- Allows the development of single protein multivalent vaccines
- May be extended to other immunogenic outer membrane proteins
- Simpler to manufacture than OMV-based vaccines
A priority patent application has been filed and Oxford University Innovation is looking for companies interested in licensing and developing the technology.
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