Evaluation of Human Immune Responses to Influenza Virus Vaccination in Healthy Volunteers
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Percentage of Subjects With Pre-vaccination Titer <1:40
研究概览
简要总结
This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants, with the aim of enrolling up to 70 participants. This study enrolled males and non-pregnant females, 18-49 years old, inclusive. The participants were screened at enrollment with a history and physical exam and laboratory testing to ensure they were healthy enough to participate. Total enrollment was 60 participants.
Qualifying participants were vaccinated with an FDA approved seasonal inactivated influenza vaccine (IIV) according to the package insert. The study enrolled a total 60 participants. The primary objective of the study was to characterize HA-specific plasmablasts and memory B cells after influenza vaccination.
Note: Due to the Coronavirus Disease 2019 (COVID-19) pandemic, all non-essential research was halted in mid-March 2020. New enrollments were placed on hold for this study. Follow-up visits were also halted, which impacted the timing of participants' subsequent follow-up visits. Five participants had their Day 180 visits halted due to the COVID-19 pandemic.
详细描述
This was an open label, single arm, Phase IV study of longitudinal immunologic responses to influenza vaccine in healthy adult participants. This study enrolled males and non-pregnant females, 18-49 years old. The primary objective of the study was to characterize hemagglutinin (HA)-specific plasmablasts and memory B cells after influenza vaccination. The secondary objective was to investigate the longevity of humoral immunity to influenza virus in humans. Total enrollment was 60 participants.
This was a multi-year study. Participant duration in this study was 180 days. Participants were screened at enrollment with a history and physical exam and laboratory testing to ensure they were healthy enough to participate. Qualifying participants were vaccinated with an FDA approved seasonal inactivated influenza vaccine (IIV) according to the package insert. Approximately 450 ml of blood was collected for the research assays during the course of the study. Specifically, 16 ml was be collected for screening; 48ml was collected at enrollment; 96ml was collected at visit Days 7 and 14; and 64 ml was collected at 28, 90, and 180 days post vaccination.
A total of 60 participants were enrolled over the course of the study. Participants who completed the study were given the option to re-enroll in subsequent years as long as they continued to meet all inclusion/exclusion criteria. Re-enrolling participants were re-consented, given new participants identifiers, and counted towards the enrollment number goal for each year of participation. Safety was assessed from the time of study enrollment through the last study visit, via monitoring of vital signs, and querying for change in health status.
Note: Due to the Coronavirus Disease 2019 (COVID-19) pandemic, all non-essential research was halted in mid-March 2020. New enrollments were placed on hold for this study. Follow-up visits were also halted, which impacted the timing of participants' subsequent follow-up visits. Five participants had their Day 180 visits halted due to the COVID-19 pandemic.
A request was submitted to the Emory University Institutional Review Board to extend the missed visit windows for the Day 180 visit for a maximum of up to 90 days, to ensure that ample time would be available to bring participants back for their missed visits. Enrollment for this study ended on September 30, 2020, before research activities could resume at Emory.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female subjects between 18 and 49 years of age, inclusive.
- •Subjects capable of providing written informed consent prior to initiation of any study procedures. Subjects able to understand and comply with planned study procedures and be available for all study visits.
- •Screening labs within normal limits per the local laboratory normal ranges or considered to be not clinically significant by the investigator. Normal laboratory ranges are as listed below:
- •Hematology:
- •Hemoglobin: Male- 12.9-16.1 gm/dL, Female- 11.4-14.4 gm/dL
- •White blood cells (WBC): Male- 4.2-9.2 upper limit (uL), Female- 4-10 upper limit (uL)
- •Platelet count: 150-400 upper limit (uL)
- •Chemistries:
- •Kidney function: Glomerular filtration rate (GFR) > / = 60 mL/min/1.73 m^2;
- •Liver enzymes: Albumin > / = 3.5 g/dL; alanine aminotransferase (ALT) <66 U/L; aspartate aminotransferase (AST) <62 U/L
- •Subjects who have not received the seasonal influenza vaccine in the current flu season and are not suspected to have had an influenza infection in the current flu season.
- •Female subjects of child bearing potential must have a negative urine pregnancy test at the screening visit, enrollment visit and all subsequent study visits longer than 14 days since the last pregnancy test.
排除标准
- •Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). This information will be obtained verbally from the patient.
- •If female, active pregnancy or breast-feeding or plans to become pregnant during study participation.
- •Chronic medical conditions that cause immunodeficiency or that require medications which could alter immune function such as immunosuppressants and immunoenhancers.
- •Have any medical disease or condition that, in the opinion of the site principal investigator or appropriate sub-investigator, is a contraindication to study participation. This includes any chronic medical disease or condition, defined as persisting 3 months (defined as 90 days) or longer, that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of this study
- •Have an acute illness, as determined by the site principal investigator or appropriate sub-investigator, within 72 hours prior to study vaccination. An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site principal investigator or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.
- •Persons taking anticoagulants, long-term aspirin therapy, or long-term systemic steroids (greater than 3 months in the past 12 months and any within 30 days).
- •Have known hypersensitivity or allergy to eggs, egg or chicken protein, or other components of the study vaccine;
- •Have a known latex allergy;
- •Have a history of severe reactions following previous immunization with licensed influenza virus vaccines.
- •Have a history of Guillain-Barre syndrome.
- •Subjects who had or are suspected to have had an influenza infection in the current influenza season.
- •Subjects who, at screening, have abnormal vital signs and/or physical exam, including a temperature > / = 38.0 C, Systolic blood pressure < / = 90 or > / = 160 mmHg, pulse < / = 60 or > 110 beats per minute, new rash, signs of infection.
- •Subjects who have already received the seasonal influenza vaccine in the current influenza vaccination season.
结局指标
主要结局
Percentage of Subjects With Pre-vaccination Titer <1:40
时间窗: Day 0
Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using RDE-treated plasma and turkey red blood cells following the WHO standard protocol. For influenza B, guinea pig red blood cells were used instead.
Percentage of Subjects Achieving Seroconversion (Pre-vaccination Hemagglutination Inhibition (HI) Titer <1:10 and a Post-vaccination HI Titer >1:40 or a Pre-vaccination HI Titer >1:10 and a Minimum Four-fold Rise in Post-vaccination HI Antibody Titer)
时间窗: Day 28
Hemagglutination inhibition titers were measured against reference influenza A/H1N1 and A/H3N2 strains, as well as influenza B Yamagata lineage influenza strains. Strains were matched to the composition of the vaccine received by each subject. For H1N1 and H3N2, hemagglutination was performed using receptor destroying enzyme (RDE)-treated plasma and turkey red blood cells following the World Health Organization (WHO) standard protocol. For influenza B, guinea pig red blood cells were used instead.
次要结局
- Endpoint Immunoglobulin G (IgG) Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein(Day 0)
- Endpoint IgG Titers for Serum Antibody Responses Directed Against the Full Length A/H1N1 Hemagglutinin (HA) Protein(Day 28)
- Expression of Human Influenza-specific Monoclonal Antibodies From Plasmablasts(Day 7)
- Plasmablast Responses Against Hemagglutinin (HA) Head Antigens Assessed by Direct ex Vivo Enzyme-linked Immunospot (ELISPOT)(Day 7)
- Frequency of Hemagglutinin (HA) Stem-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells(Day 28)
- Function of Human Influenza-specific Monoclonal Antibodies Assessed by Virus Neutralization Assay(Day 7)
- Function of Human Influenza-specific Monoclonal Antibodies Assessed by Enzyme-Linked Immunosorbent Assay (ELISA)(Day 7)
- Function of Human Influenza-specific Monoclonal Antibodies Assessed by Hemagglutination Inhibition (HAI) Assay(Day 7)
- Quadrivalent Influenza Vaccine IgG1 ELISA Endpoint Titer(Day 28)
- Frequency of Hemagglutinin (HA) Head-specific IgG Secreting Memory B Cells Per Total IgG Secreting Cells(Day 28)
- Quadrivalent Influenza Vaccine Immunoglobulin Gamma-1 (IgG1) ELISA Endpoint Titer(Day 0)
- Plasmablast Responses Against Hemagglutinin (HA) Stem Antigens Assessed by Direct ex Vivo Enzyme-linked Immunospot (ELISPOT)(Day 7)
- Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region(Day 180)
- Endpoint IgG Titers for Serum Antibody Responses Directed Against the H1N1 Hemagglutinin (HA) Stem Region.(Day 28)