Clinical trial NCT03686514: The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics
Official title: The Impact of Imprinting and Repeated Influenza Vaccination on Adaptive Immunity, Transcriptomics, and Metabolomics
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Influenza
Keywords: Flu vaccine
Influenza vaccine
Immune response
Influenza strain
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2018-09-27
Enrollment: 39
Sex: ALL
Minimum age (years): 42
Maximum age (years): 71
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this study is to understand the impact on the human immune system's response to the four strain flu vaccine in individuals who have "imprinted" on specific influenza strains. It will also consider the effects of repeated prior annual influenza vaccination on the immune system.

Detailed description: Seasonal influenza outbreaks continue to cause substantial disease burden, with an estimated 3-5 million cases of severe illness, and 250,000 to 500,000 deaths worldwide each year. In the United States, the Centers for Disease Control and Prevention (CDC) reports that influenza has resulted in 9.2-35.6 million illnesses with 12,000-56,000 deaths annually since 2010. There is an urgent need to better understand the immunologic responses to current licensed vaccines in order to develop a more effective vaccine that does not rely on annual updates, provides broad protection, and is durable; i.e., a universal influenza vaccine.

The immune response to the influenza vaccine is affected by many parameters, including prior imprinting to a specific influenza strain based on birth cohort, as well as prior influenza vaccination. The FDA-approved, quadrivalent seasonal influenza vaccine that will be administered contains four distinct strains, two influenza A viruses (IAVs) and two influenza B viruses (IBVs). The approved seasonal influenza vaccine will be given for each season of influenza: 2018-2019, 2019-2020, and 2020-2021.

This study is a prospective pilot study conducted over the course of three years (with three specific influenza seasons studied). For each year (2018-2019, 2019-2020, and 2020-2021), two cohorts of 10 participants each, who are in good health and meet all eligibility criteria, will be recruited. The influenza A virus subtype H3N2 cohort (N=30 total, 10 per year) will consist of participants born between 1968-1977, and the influenza A virus subtype H1N1 cohort (N=30 total, 10 per year) will consist of participants born between 1948-1957. Each participant will make a total of six visits to the Hope Clinic. Day 1 will include the informed consent process, and screening to ensure the subject meets all inclusion criteria and meets no exclusion criteria. For the consenting and eligible subject, the visit will also include pre-vaccination phlebotomy for baseline immunogenicity laboratory assays. After baseline sample collection, the participants will receive the FDA-approved seasonal influenza vaccine. Subsequent study visits up to 180 days post-vaccination will include collection for immunogenicity assays.

This study is not powered to test a formal null hypothesis. Rather, it is a hypothesis-generating investigation that will hopefully lead to larger trials based on the findings. The study will be conducted over the course of three years to increase the total sample population size and to validate the findings over different influenza seasons.

Eligibility criteria: Inclusion Criteria:

1. Capable of informed consent and provision of written informed consent before any study procedures.
2. Capable of attending all study visits according to the study schedule.
3. Males or females born between 1968-1977 or 1948-1957.
4. Are in good health, as determined by medical history and targeted physical exam related to this history.
5. Oral temperature is less than 38 degrees Celsius.
6. Resting pulse rate is between 50 and 100 beats per minute.
7. Female subjects of childbearing age must have a negative urine pregnancy test within 24 hours before study vaccination.
8. Have received the influenza vaccine at least 3 of the past 5 years or have received the influenza vaccine in 2 or less of the past 5 years.

Exclusion Criteria:

1. Have an acute illness within 72 hours before vaccination.
2. Have any condition that, in the opinion of the principal investigator, would place the subject at an unacceptable risk of harm or confound the interpretation of the study results.
3. Have any acute or chronic medical condition that, in the opinion of the principal investigator, would make vaccination unsafe or interfere with the evaluation of immune response to study vaccination.
4. Have a suppressed immune system as a result of illness, immunosuppressive medication, chemotherapy, or radiation therapy within 3 years prior to study vaccination.
5. Have known HIV, hepatitis B, or hepatitis C infection.
6. Have a known history of autoimmune disease.
7. Have taken oral or parenteral corticosteroids of any dose within 30 days before study vaccination.
8. Have taken high-dose inhaled corticosteroids within 30 days before study vaccination.
9. Have received, or plan to receive, any licensed live vaccine within 30 days, or any licensed inactivated vaccine within 14 days, prior to, or after, study vaccination.
10. Have planned receipt of any unlicensed or investigational medications, biologics, or vaccines for the duration of subject study participation.
11. Have received immunoglobulin or other blood products, with the exception of Rho D immunoglobulin, within 90 days prior to study vaccination.
12. Have donated blood or blood products within 30 days before study vaccination, or within 60 days after study vaccination, or plan to donate blood within 30 days of the last blood draw.
13. Have known hypersensitivity or allergy to eggs, egg protein, chicken protein, or other compounds of the study vaccine.
14. Have a history of severe reactions following vaccination with influenza virus vaccines.

Primary outcomes:
measure: The Number of Participants Achieving Seroprotection Against Each Strain
timeFrame: 28 days after vaccination
measure: The Number of Participants Achieving Seroconversion Against Each Strain
timeFrame: 28 days after vaccination
measure: Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
timeFrame: 28 days after vaccination
Secondary outcomes:
measure: The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by Neutralizing Antibody (NAb) Response
timeFrame: 28 days after vaccination
measure: Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
timeFrame: 28 days after vaccination
measure: The Number of Participants Achieving Seroprotection Against Each Strain
timeFrame: 180 days after vaccination
measure: The Number of Participants Achieving Seroconversion Against Each Strain
timeFrame: 180 days after vaccination
measure: Geometric Mean Titers (GMTs) of Serum HAI Against Each Strain
timeFrame: 180 days after vaccination
measure: The Proportion of Participants Achieving Seroprotection or Seroconversion Against Each Strain Measured by NAb Response
timeFrame: 180 days after vaccination
measure: Geometric Mean Titers (GMTs) of Serum NAb Against Each Strain
timeFrame: 180 days after vaccination
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: The Hope Clinic of the Emory Vaccine Center
state: Georgia
Study officials:
affiliation: Emory University
name: Nadine Rouphael, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sherman AC, Lai L, Bower M, Natrajan MS, Huerta C, Karmali V, Kleinhenz J, Xu Y, Rouphael N, Mulligan MJ. The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination. Vaccines (Basel). 2020 Nov 7;8(4):663. doi: 10.3390/vaccines8040663.