Understanding the Immune Response to Meningitis Vaccines

In this single centre, open-label, randomised, controlled study of 150 healthy adults aged 18-70 years we will be evaluating the immune response to immunisation with 2 different vaccines against 4 related bacteria known as Neisseria meningitidis serogroups A, C, W-135 and Y. These bacteria (also known as meningococci) can produce meningitis and septicaemia (blood poisoning). The first vaccine, which has been used as a travel vaccine in the UK for several years, is known as the MenACWY plain polysaccharide (MenACWY PS). The other vaccine, known as the MenACWY conjugate vaccine (MenACWY) was licensed in the UK in March 2010 and is now recommended as a travel vaccine by the Department of Health.

In order to evaluate the immune response to these vaccines we will be measuring not only the blood levels of antibodies specific to serogroup A, C, W-135 and Y meningococci, but also the population of white blood cells known as B cells which produce these antibodies. Two forms of these B cells will be measured, the plasma cells (which actively produce antibodies) and memory B cells (which do not produce antibodies but persist in the body and can be stimulated to turn into plasma cells when required).

Participants will be randomised into group I or group II on a 1:1 basis to receive either MenACWY or MenACWY PS. One month later, all participants will receive a booster dose of the MenACWY conjugate vaccine. The ACWY polysaccharide vaccine will be administered subcutaneously, and the MenACWY conjugate vaccine will be given intramuscularly. Each participant will be observed for at least 15 minutes after vaccination for any immediate reactions.

Blood samples will be collected from each participant for analysis prior to each immunisation, 7 days following the first immunisation and 7 and 28 days following the second immunisation. The volume of blood samples obtained at each timepoint will be 20 mLs. Blood will be used for antibody analysis (by ELISA), B cell analysis (by ELISpot)and DNA extraction for genetic analysis.

In summary, participants enrolled in this study will have a total of 5 visits in a period of 2 months. They will receive two doses of the MenACWY conjugate vaccine or one dose of the ACWY polysaccharide vaccine followed by one dose of the MenACWY conjugate vaccine. During this period they will have a total of 5 blood samples taken (5x20mL= 100 mL of blood taken in a 2 month period).

Inclusion criteria

• Participant is willing and able to give informed consent for participation after the nature of the study has been explained
• Male or Female, aged 18- 70 years inclusive
• In good health as determined by:

• Medical history
• History-directed physical examination
• Clinical judgment of the investigator
• Female participants of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
• Able (in the Investigator's opinion) and willing to comply with all study requirements
• Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study

Exclusion criteria

• Are unwilling or unable to give written informed consent to participate in the study
• Have previously received any meningococcal vaccine (this will be confirmed with the participant's general practitioner after enrolment)
• Have previously been diagnosed with laboratory confirmed meningococcal disease
• Have a history of any anaphylactic shock, asthma, urticaria or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component
• Have a known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):

• Receipt of any immunosuppressive therapy
• Congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months or long-term systemic corticosteroid therapy* (*prednisolone or equivalent for more than two consecutive weeks within the past 3 months).
• Have a suspected or known HIV infection or HIV related disease
• Have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months
• Have a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time
• Have any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives
• Participation in another clinical trial investigating a vaccine, a drug, a medical device, or a medical procedure
• Pregnancy as confirmed by a positive pregnancy test
• Currently breast-feeding