Defining the expression of MenB vaccine genes by meningococci at different phases and densities of colonisation

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Professor Adam Finn, Dr Hannah Christensen


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Rationale

Meningococcal meningitis and septicaemia are rare but severe infections; in the UK most cases are caused by group B. A new meningococcal vaccine containing protein antigens (Bexsero) has been recommended for UK infants (subject to a cost-effective price). Another similar vaccine (Trumenba) has been licensed in the USA. If these vaccines affect pharyngeal colonisation and transmission of meningococci, which occur most commonly in adolescents, an alternative strategy may be to immunise this age group to generate indirect effects as were seen with conjugate group C vaccines. Any vaccine induced mucosal immune responses affecting transmission will depend upon levels of expression of the vaccine antigens by bacteria at different phases of colonisation. Novel transcriptomic techniques permit accurate absolute quantification of numbers of mRNA transcripts in biological samples providing a means of measuring whether certain bacterial genes are up- or downregulated in specific circumstances.

Aims & objectives

-To elucidate bacterial transcription signatures for different stages and densities of colonisation of the human pharynx that will permit prediction of vaccine impact upon acquisition and clearance of meningococci
Objectives:
- Establish mRNA transcript detection assays for a panel of meningococcal proteins including those in the two "MenB" vaccines and other surface expressed proteins

Methods

The Bristol HPRU is currently conducting a longitudinal study (over 6 months) detecting and quantifying meningococcal pharyngeal carriage in ~800 16-18 year old school students. Assays will first be established using RNA derived from cultures of standard meningococcal strains done under conditions designed to mimic different levels of stress (variation in nutrients temperature etc.) as well as pharyngeal swabs taken into RNA preservation medium from individuals with detectable meningococcal carriage.
Gene expression profiles will then be described using samples from carriers with low and high density pharyngeal colonisation, individuals who have acquired detectable carriage de novo within the previous month and individuals who have had detectable colonisation for at least 3 months.
Later in the project it may also be feasible to compare bacterial gene expression in colonised individuals who have received MenB vaccines with others who have not.

References


Created on Oct. 1, 2015, 9 a.m.