Understanding the Immune Response to Meningitis Vaccines
Understanding the Immune Response to Meningitis Vaccines
The purpose of the study is to evaluate and compare the immune response to two vaccines
 against 4 related bacteria: meningococcal serogroups A, C, W-135 and Y. These bacteria can
 cause meningitis and /or septicaemia (blood poisoning). The two vaccines are a
 protein-polysaccharide conjugate vaccine (MenACWY)and a meningococcal plain polysaccharide
 vaccine(MenACWY PS). Both vaccines are licensed and are currently used for travellers to
 areas with a high incidence of invasive meningococcal disease. However, plain polysaccharide
 vaccines are known to be poorly immunogenic in children and they do not stimulate
 immunological memory, apart from the serogroup A component. In contrast, a
 protein-polysaccharide conjugate vaccine against meningococcal serogroups A, C, W-135 and Y
 has been found to be immunogenic in infants and to be able to induce immunological memory.

 The proposed study is a single centre, open-label, randomised, controlled study in 150
 healthy adults aged 18-70 years. The participants will be given either 2 injections of the
 meningococcal protein-polysaccharide conjugate vaccine one month apart, or one injection of
 the meningococcal plain polysaccharide vaccine followed one month later with an injection of
 the meningococcal conjugate vaccine. Blood samples will be collected before immunisation and
 at several time points following immunisations to evaluate the level of meningococcal
 specific antibody induced by two different vaccination regimes. The data derived from the
 study will be relevant in determining which of these vaccines should be used in preference in
 travellers who are receiving immunisation against meningococcal disease before travelling to
 high risk areas. Additionally, a number of scientific questions regarding the nature of the
 immune response to the two vaccines (specifically looking at the white blood cells
 responsible for producing antibodies, known as B cells) and the role of genetic variations in
 influencing the vaccine recipient's immune response will be addressed in the study.
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