Investigating the Immune Response to 4CMenB in Infants

The incidence of meningococcal disease is 0.2-14 per 100,000 in industrialized countries. In England and Wales, during the period 2005-2010, there were 900-1300 cases annually. Disease is commonest in infants, young children and adolescents and case fatality is high at 8-10%.

Until recently there were no licensed vaccines against serogroup B meningococcal disease, although vaccines against epidemic strains of MenB have been used in several countries.

Unfortunately, 4CMenB is associated with significant reactogenicity. This is presumably related to the presence of various bacterial surface components present in the outer membrane vessicles (OMVs), including lipopolysacchride (LPS), which are capable of activating the innate immune response. The host pathways responsible for reactogenicity to OMV vaccines, and indeed to other vaccines, are not yet established, and the relationship between reactogenicity and immunogenicity is not clear.

This study will provide information about pathways and mechanisms of immunity and may identify gene expression signals which can be used in future vaccine design and evaluation.

Inclusion criteria

• Healthy infants of two Caucasian parents (self-defined by parent) born between 37 and 42 weeks of gestation aged 8-12 weeks at time of first visit
• Parent or legal guardian willing and able to comply with the requirements of the protocol and have internet access for the duration of the study.
• Parent/legal guardian who have given informed consent for their child's participation in the study

Exclusion criteria

• Non-Caucasian infants
• Children of parents who are on the delegation log for this study
• Parent/ legal guardian under the age of 18
• History of invasive meningococcal B disease
• Previous vaccination with meningococcal serogroup B vaccine
• History of being a household contact with a case of confirmed bacterial meningitis
• Prior administration of any vaccine or planned administration of any vaccine not specified in the study protocol, with the exception of Hepatitis B vaccine and Influenza vaccines (which can be given 14 days before or after study vaccines), or BCG (which can be administered 28 days before or after study vaccines)
• Prior or planned receipt of any other investigational vaccine or drug
• Confirmed or suspected immunodeficiency
• A family history of congenital or hereditary immunodeficiency, or maternal HIV
• Receipt of more than 1 week of immunosuppressants or immune modifying drugs (e.g. oral prednisolone >0.5ml/kg/day or intravenous glucocorticoid steroid).
• History of allergy to any component of the vaccine
• Major congenital defects or serious chronic illness
• History of any neurologic disorders or seizures
• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period
• Any other condition which, in the opinion of the investigator, may interfere with the ability to fulfil study requirements (this may include plans to move house and language comprehension).
• No internet access for the duration of the study.