An Open Label Study of IgG Fc Glycan Composition in Human Immunity
试验速览
- 阶段
- 不适用
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- The Percent (of 100%) of IgG With Galactosylation, Fucosylation and/or Sialylation
研究概览
简要总结
In order to produce better more effective vaccines, it is important to understand the particulars of why individuals have an effective or ineffective immune response to vaccination. We are going to examine specific aspects of the antibody (IgG Fc glycan) made by healthy volunteers who receive different vaccines or who have a viral infection to understand the nature of an effective (or less effective) vaccine response. The results of this research could be used to develop adjuvants to increase/ improve vaccine response.
详细描述
Antibodies are principle mediators of immunity against infections and they can also give rise to autoimmune and inflammatory diseases. Two functional domains make up an IgG antibody - the Fab domain binds to a specific target, while the Fc domain can interact with receptor molecules to activate a pro- or anti- inflammatory state. The Fc domain of IgGs contains a glycan that is variable in composition and its specific sugar components are an important determinant of the biologic activity of IgGs in both protective and pathologic immune responses. New disease treatments could be developed through purposeful manipulation of IgG Fc glycans, but there is currently little known about how Fc glycan composition is regulated. We plan to study this by evaluating whether vaccination can cause changes in Fc glycan composition and, if so, whether signaling from helper T cells, age of the patient, and/or route of vaccine administration are determinants of specific modifications that are triggered by vaccination. Next, we will study effects that specific components within the Fc glycan have on immunity against the common human pathogens Streptococcus pneumoniae and influenza viruses using in vitro and in vivo models of infection. We will also study whether healthy adults who have been previously infected with dengue, zika or chikungunya virus generate distinct Fc glycoforms after vaccination compared with healthy adults who have not been previously infected with any of these viruses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or Female 18-80 years of age
- •Healthy volunteers without significant medical problems
- •Able to give informed consent to participate
- •Willing to receive a single dose of an FDA-approved vaccine (either the influenza virus, pneumococcal or meningococcal vaccine)
- •Documented previous infection with dengue, zika or chikungunya virus or no history of dengue, zika or chikungunya infection.
排除标准
- •Prior allergic reaction to commercial vaccination
- •For Flumist participants: Close contact with person with severely compromised immune system requiring isolation
- •For Flumist participants: Current illness that limits delivery to nasal airway (mild illness, such as diarrhea or mild respiratory infection with or without fever, and local infections do not apply)
- •History of seizure disorder for Flumist group participants only.
- •Participation in another clinical study of an investigational product currently or within the past 90 days, or expected participation during this study.
- •Any clinically significant acute or chronic medical condition requiring care of a physician (e.g., diabetes, coronary artery disease, rheumatologic illness, malignancy, substance abuse) that, in the opinion of the investigator, would preclude participation.
- •In the opinion of the investigator, the volunteer is unlikely to comply with the study protocol.
- •Currently taking systemic steroids or other immunomodulatory medications including anticancer medications and antiviral medications.
- •Egg allergy
- •Received the influenza vaccine less than 1 month ago and/or received the pneumococcal and meningococcal vaccine less than 4 years ago
- •Confirmed HIV infection, positive for hepatitis B surface antigen or positive for hepatitis C antibodies.
- •Is pregnant or lactating
- •History of Guillain-Barre syndrome
- •Poor venous access
- •Unable to continue participation for 12 weeks
- •Any clinically significant abnormality on medical history or physical examination including history of immunodeficiency or autoimmune disease.
研究组 & 干预措施
Biologic/Vaccine, Age 18-64 cohort
Vaccination. IM Pneumococcal, meningococcal, or flu vaccine
干预措施: IM Pneumococcal, meningococcal, or flu vaccine (Biological)
Biologic/Vaccine, Age 65-80 cohort
Vaccination. IM Pneumococcal, meningococcal, or flu vaccine
干预措施: IM Pneumococcal, meningococcal, or flu vaccine (Biological)
Vaccine, healthy adults
Vaccination. IM Pneumococcal, meningococcal, or flu vaccine
干预措施: IM Pneumococcal, meningococcal, or flu vaccine (Biological)
结局指标
主要结局
The Percent (of 100%) of IgG With Galactosylation, Fucosylation and/or Sialylation
时间窗: One Day
The percent of Fc glycans that are galactosylation, fucosylation and/or sialylation of pre- vs. post- vaccination Fcs determined by lectin blot (Erythrina cristagalli, Aleuria Aurantia Lectin and Sambucus nigra lectins specific for galactose, fucose and 2,6-sialic acid, respectively) or by mass spectrometric analysis. 100% of IgG were found to have these modifications.
次要结局
未报告次要终点