A Single Centre, Open-label, Randomised Clinical Study to Investigate Meningococcal Serogroup A and C Saccharide Specific B Cell Responses in Adult Volunteers to One of Three Regimens of Meningococcal ACWY Conjugate Vaccine or Meningococcal ACWY Polysaccharide Vaccine Priming Doses Followed by a Booster Dose of the Meningococcal ACWY Conjugate Vaccine
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- phenotype of meningococcal serogroup A specific B cells
研究概览
简要总结
The bacterium (germ) Neisseria meningitidis causes meningitis and blood poisoning. N meningitidis is classified into different serogroups (types), based on its outer polysaccharide (carbohydrate) capsule. Serogroups A,B,C,W & Y are responsible for the vast majority of meningococcal disease worldwide.
Older vaccines against types A,C,W & Y contain part of the polysaccharide capsule of the germ. However, these polysaccharide vaccines do not provide long-term protection against disease and are less effective in young children, the group most at risk of meningococcal disease. Newer "conjugate" ACWY vaccines attach a polysaccharide to a protein carrier - these provoke a good response in young children and can provide long-term protection.
White blood cells called B cells produce antibodies, which are the main components of protection against meningococcal disease. Although many studies have investigated the immune response to these vaccines in different age groups by measuring specific antibodies, there is limited information about the B cells underlying such an immune response. Several different subsets (populations) of B cells exist in the blood. Previous studies by the investigators group suggest that different numbers of B cells are produced in response to each vaccine type. However, little is understood about which subset of B cell is important for antibody production in response to these polysaccharide or conjugate vaccines.
This study aims to provide detailed information on the immune response to meningococcal vaccines by investigating the appearance of B cells and their subsets in the blood after vaccination with the polysaccharide and conjugate vaccines. These observations will help us understand how polysaccharide and conjugate vaccines stimulate the immune system in different ways. This knowledge will help in the development of new vaccines that are effective across all age groups.
The investigators aim to recruit 20 adults aged 30-70 from Oxfordshire. The study will be funded by the Oxford Vaccine Group.
详细描述
EPIDEMIOLOGY
Neisseria meningitidis is a globally important cause of meningitis and septicaemia. The polysaccharide capsule is an important virulence factor in causing invasive disease. The serogroup of a meningococcal strain is determined by the biochemical composition of the polysaccharide capsule. There are 13 diverse polysaccharide capsules but only A, B, C, W and Y commonly cause invasive infections. In particular serogroups A,C,W, & Y account for >70% of meningococcal disease in North America, serogroups B & C are responsible for the vast majority of disease in Europe and Serogroup A causes cyclical meningitis epidemics in the African meningitis belt, including the recent outbreak in 2009/2010.
Given the rapid progression and serious sequelae of meningococcal disease, primary prevention is vital and this is most effectively achieved by vaccination. In the absence of a serogroup B vaccine, quadrivalent vaccines against serogroups ACW & Y represent the broadest mechanism of control of meningococcal disease worldwide. Protection induced by these vaccines relies on anti-capsular polysaccharide antibodies.
MENINGOCOCCAL POLYSACCHARIDE AND CONJUGATE VACCINES
Polysaccharide ACWY vaccines consist of pure capsular polysaccharide from each of the four serogroups and have been in widespread use since the late 1970's. However, in common with polysaccharide vaccines against other encapsulated bacteria, meningococcal polysaccharide vaccines are poorly immunogenic in young children, do not provoke long lasting immune responses[5] and may not reduce nasopharyngeal carriage. Newer conjugate vaccines consist of capsular oligosaccharides chemically linked to a protein carrier. Conjugation of a polysaccharide to a protein carrier allows the recruitment of cognate T cell help with subsequent exposure to antigen provoking a potentiated antibody response and immunological memory.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must meet the following conditions in order to be enrolled:
- •Between 30 and 70 years of age inclusive;
- •Willing and able to give informed consent for participation after the nature of the study has been explained;
- •In good health as determined by:
- •medical history history-directed physical examination clinical judgment of the investigator
- •Able (in the Investigators opinion) and willing to comply with all study requirements including be available for all the visits scheduled in the study;
- •Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
排除标准
- •Participants with any of the following conditions or characteristics will be excluded from study enrolment:
- •Prior receipt of a meningococcal vaccine;
- •Prior laboratory confirmed disease caused by N meningitides;
- •Prior history of any anaphylactic shock, asthma, urticarial or other allergic reaction after previous vaccinations or known hypersensitivity to any vaccine component;
- •Known or suspected autoimmune disease or impairment /alteration of immune function resulting from (for example):
- •Receipt of immunostimulants
- •Congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding year or long-term systemic corticosteroid therapy (prednisolone or equivalent for more than two consecutive weeks within the past 3 months).
- •Suspected or known HIV infection or HIV related disease;
- •Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 3 months
- •Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time;
- •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 ;
- •Concurrent breast-feeding.
研究组 & 干预措施
Group 1 Conjugate-conjugate
Group I will receive 2 doses of the MenACWY-CRM conjugate vaccine (Novartis Vaccines) given 1 month apart. All vaccine doses are 0.5ml and will be administered intramuscularly into the deltoid.
干预措施: MenACWY-CRM conjugate vaccine (Menveo, Novartis) (Biological)
Group 2 Polysaccharide-conjugate
Group II will receive one full dose of MenACWY-PS polysaccharide vaccine meningococcal vaccine, followed by one dose of MenACWY-CRM conjugate vaccine given 1 month later.
0.5 mL of MenACWY-PS vaccine will be administered subcutaneously and 0.5 mL of the MenACWY-CRM vaccine will be administered intramuscularly into the deltoid.
干预措施: MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis) (Biological)
Group 3 Polysaccharide (subcutaneously)-conjugate
Group III will receive a full dose of MenACWY-PS polysaccharide vaccine meningococcal vaccine subcutaneously, followed by one dose of MenACWY-CRM conjugate vaccine given 1 month later.
干预措施: MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis) (Biological)
Group 3 Polysaccharide (subcutaneously)-conjugate
Group III will receive a full dose of MenACWY-PS polysaccharide vaccine meningococcal vaccine subcutaneously, followed by one dose of MenACWY-CRM conjugate vaccine given 1 month later.
干预措施: 1/5th dose MenACWY-PS polysaccharide vaccine, ( ACWYVax, GSK) and MenACWY-CRM conjugate vaccine (Menveo, Novartis) (Biological)
Group 4: 1/5th dose Polysaccharide:conjugate
Group IV will receive one fifth dose of MenACWY-PS polysaccharide vaccine meningococcal vaccine, followed by one dose of MenACWY-CRM conjugate vaccine given 1 month later.
0.1 mL of MenACWY-PS vaccine will be administered IM and 0.5 mL of the MenACWY-CRM vaccine will be administered intramuscularly into the deltoid.
干预措施: Polysaccharide (subcutaneously)-conjugate (Biological)
结局指标
主要结局
phenotype of meningococcal serogroup A specific B cells
时间窗: 7 days after immunisation
The phenotype of meningococcal serogroup A specific B cells will be observed at day 7 following the initial immunisation with full dose quadrivalent meningococcal polysaccharide vaccine, 1/5th dose quadrivalent meningococcal polysaccharide vaccine and quadrivalent meningococcal conjugate vaccine by Fluorescent Activated Cell Sorting (FACS) analysis. This will be performed at the laboratories of the Oxford Vaccine Group, University of Oxford.
次要结局
- The phenotype of meningococcal serogroup C specific B cells(7 days after immunisation)
- The measurement of meningococcal serogroup A and C specific memory B cells(28 days after immunisation)
- The phenotype of meningococcal serogroup A specific B cells(28 days after immunisation)
- The measurement of meningococcal serogroup A and C specific plasma cells(7 days after immunisation)
- The phenotype of meningococcal serogroup C specific B cells(28 days after immunisation)