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Evaluation of the Effects of Age, Prior Exposure, and Previous Vaccination on B Cell Response to Influenza Vaccine in Healthy Adults and Children

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ClinicalTrials.gov Identifier: NCT03328325
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : December 14, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
The study will be designed as a prospective surveillance of the immune response to seasonal influenza vaccination in 240 healthy children and adults ages 9 and over. Study duration will be 5 years, with a participant duration of 6 months. Subjects will receive Fluarix (GSK) quadrivalent inactivated influenza vaccine, at a dose of not less than 15 ug of hemagglutinin (HA), by intramuscular injection in open label fashion on day 0. Blood draws will occur at baseline, day 7, 28 and 90. The primary objective of this study is to evaluate the relationship between first influenza A virus exposure (inferred by age), vaccine history, and baseline serum antibody and Memory B cell (MBC) specificity, and the magnitude and breadth of the subsequent B cell response to seasonal influenza vaccine in healthy adults and children.

Condition or disease Intervention/treatment Phase
Influenza Influenza Immunisation Biological: Influenza Virus Quadrivalent Inactivated Vaccine Phase 4

Detailed Description:
The study will be designed as a prospective surveillance of the immune response to seasonal influenza vaccination in 240 healthy children and adults ages 9 and over. Study duration will be 5 years, with a participant duration of 6 months. Subjects will receive Fluarix (GSK) quadrivalent inactivated influenza vaccine, at a dose of not less than 15 ug of hemagglutinin (HA), by intramuscular injection in open label fashion on day 0. Blood draws will occur at baseline, day 7, 28 and 90. The primary hypothesis being tested in this study is that there will be differences in the specificity and magnitude of the HA-specific B cell response depending on the age, previous vaccine history and baseline B cell reactivity. The primary objective of this study is to evaluate the relationship between first influenza A virus exposure (inferred by age), vaccine history, and baseline serum antibody and Memory B cell (MBC) specificity, and the magnitude and breadth of the subsequent B cell response to seasonal influenza vaccine in healthy adults and children. The secondary objective is to determine the durability of the antibody response and relationship between acute and durable antibody.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Evaluation of the Effects of Age, Prior Exposure, and Previous Vaccination on the B Cell Response to Inactivated Influenza Vaccine in Healthy Adults and Children
Actual Study Start Date : December 20, 2017
Estimated Primary Completion Date : October 11, 2022
Estimated Study Completion Date : December 11, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: Fluarix
0.5 mL dose of IIV-4 vaccine administered intramuscularly, n=240
Biological: Influenza Virus Quadrivalent Inactivated Vaccine
A seasonal quadrivalent inactivated influenza vaccine (IIV4), prepared from influenza viruses propagated in embryonated chicken eggs, protecting against 2 influenza A subtypes and 2 influenza B subtypes.




Primary Outcome Measures :
  1. Frequency of ASC stratified by age group [ Time Frame: Day 7 ]
  2. Frequency of ASC stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  3. Frequency of ASC stratified by vaccine history [ Time Frame: Day 7 ]
  4. Frequency of peripheral blood antibody secreting cells (ASC) overall [ Time Frame: Day 7 ]
  5. Frequency of peripheral blood memory B cells (PMBC) overall [ Time Frame: Day 28 ]
  6. Frequency of PMBC stratified by age group [ Time Frame: Day 28 ]
  7. Frequency of PMBC stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  8. Frequency of PMBC stratified by vaccine history [ Time Frame: Day 28 ]
  9. Magnitude of the serum antibody response by genome fragment phage display (GFPD) overall [ Time Frame: Day 7 ]
  10. Magnitude of the serum antibody response by GFPD overall [ Time Frame: Day 28 ]
  11. Magnitude of the serum antibody response by GFPD stratified by age group [ Time Frame: Day 28 ]
  12. Magnitude of the serum antibody response by GFPD stratified by age group [ Time Frame: Day 7 ]
  13. Magnitude of the serum antibody response by GFPD stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  14. Magnitude of the serum antibody response by GFPD stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  15. Magnitude of the serum antibody response by GFPD stratified by vaccine history [ Time Frame: Day 28 ]
  16. Magnitude of the serum antibody response by GFPD stratified by vaccine history [ Time Frame: Day 7 ]
  17. Magnitude of the serum antibody response by HAI overall [ Time Frame: Day 28 ]
  18. Magnitude of the serum antibody response by HAI stratified by age group [ Time Frame: Day 28 ]
  19. Magnitude of the serum antibody response by HAI stratified by age group [ Time Frame: Day 7 ]
  20. Magnitude of the serum antibody response by HAI stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  21. Magnitude of the serum antibody response by HAI stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  22. Magnitude of the serum antibody response by HAI stratified by vaccine history [ Time Frame: Day 28 ]
  23. Magnitude of the serum antibody response by HAI stratified by vaccine history [ Time Frame: Day 7 ]
  24. Magnitude of the serum antibody response by hemagglutination-inhibition (HAI) overall [ Time Frame: Day 7 ]
  25. Magnitude of the serum antibody response by Hemagglutinin Array assay overall [ Time Frame: Day 28 ]
  26. Magnitude of the serum antibody response by Hemagglutinin Array assay overall [ Time Frame: Day 7 ]
  27. Magnitude of the serum antibody response by Hemagglutinin Array assay stratified by age group [ Time Frame: Day 28 ]
  28. Magnitude of the serum antibody response by Hemagglutinin Array assay stratified by age group [ Time Frame: Day 7 ]
  29. Magnitude of the serum antibody response by Hemagglutinin Array assay stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  30. Magnitude of the serum antibody response by Hemagglutinin Array assay stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  31. Magnitude of the serum antibody response by Hemagglutinin Array assay stratified by vaccine history [ Time Frame: Day 28 ]
  32. Magnitude of the serum antibody response by Hemagglutinin Array assay stratified by vaccine history [ Time Frame: Day 7 ]
  33. Magnitude of the serum antibody response by microneutralization (MN) overall [ Time Frame: Day 7 ]
  34. Magnitude of the serum antibody response by MN overall [ Time Frame: Day 28 ]
  35. Magnitude of the serum antibody response by MN stratified by age group [ Time Frame: Day 28 ]
  36. Magnitude of the serum antibody response by MN stratified by age group [ Time Frame: Day 7 ]
  37. Magnitude of the serum antibody response by MN stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  38. Magnitude of the serum antibody response by MN stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  39. Magnitude of the serum antibody response by MN stratified by vaccine history [ Time Frame: Day 28 ]
  40. Magnitude of the serum antibody response by MN stratified by vaccine history [ Time Frame: Day 7 ]
  41. Magnitude of the serum antibody response by SPR overall [ Time Frame: Day 28 ]
  42. Magnitude of the serum antibody response by SPR stratified by age group [ Time Frame: Day 28 ]
  43. Magnitude of the serum antibody response by SPR stratified by age group [ Time Frame: Day 7 ]
  44. Magnitude of the serum antibody response by SPR stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  45. Magnitude of the serum antibody response by SPR stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  46. Magnitude of the serum antibody response by SPR stratified by vaccine history [ Time Frame: Day 28 ]
  47. Magnitude of the serum antibody response by SPR stratified by vaccine history [ Time Frame: Day 7 ]
  48. Magnitude of the serum antibody response by surface plasmon resistance (SPR) overall [ Time Frame: Day 7 ]
  49. Specificity of ASC overall [ Time Frame: Day 7 ]
  50. Specificity of ASC stratified by age group [ Time Frame: Day 7 ]
  51. Specificity of ASC stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  52. Specificity of ASC stratified by vaccine history [ Time Frame: Day 7 ]
  53. Specificity of PMBC overall [ Time Frame: Day 28 ]
  54. Specificity of PMBC stratified by age group [ Time Frame: Day 28 ]
  55. Specificity of PMBC stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  56. Specificity of PMBC stratified by vaccine history [ Time Frame: Day 28 ]
  57. Specificity of the serum antibody response by GFPD overall [ Time Frame: Day 28 ]
  58. Specificity of the serum antibody response by GFPD overall [ Time Frame: Day 7 ]
  59. Specificity of the serum antibody response by GFPD stratified by age group [ Time Frame: Day 28 ]
  60. Specificity of the serum antibody response by GFPD stratified by age group [ Time Frame: Day 7 ]
  61. Specificity of the serum antibody response by GFPD stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  62. Specificity of the serum antibody response by GFPD stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  63. Specificity of the serum antibody response by GFPD stratified by vaccine history [ Time Frame: Day 28 ]
  64. Specificity of the serum antibody response by GFPD stratified by vaccine history [ Time Frame: Day 7 ]
  65. Specificity of the serum antibody response by HAI overall [ Time Frame: Day 28 ]
  66. Specificity of the serum antibody response by HAI overall [ Time Frame: Day 7 ]
  67. Specificity of the serum antibody response by HAI stratified by age group [ Time Frame: Day 28 ]
  68. Specificity of the serum antibody response by HAI stratified by age group [ Time Frame: Day 7 ]
  69. Specificity of the serum antibody response by HAI stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  70. Specificity of the serum antibody response by HAI stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  71. Specificity of the serum antibody response by HAI stratified by vaccine history [ Time Frame: Day 28 ]
  72. Specificity of the serum antibody response by HAI stratified by vaccine history [ Time Frame: Day 7 ]
  73. Specificity of the serum antibody response by Hemagglutinin Array assay overall [ Time Frame: Day 28 ]
  74. Specificity of the serum antibody response by Hemagglutinin Array assay overall [ Time Frame: Day 7 ]
  75. Specificity of the serum antibody response by Hemagglutinin Array assay stratified by age group [ Time Frame: Day 28 ]
  76. Specificity of the serum antibody response by Hemagglutinin Array assay stratified by age group [ Time Frame: Day 7 ]
  77. Specificity of the serum antibody response by Hemagglutinin Array assay stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  78. Specificity of the serum antibody response by Hemagglutinin Array assay stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  79. Specificity of the serum antibody response by Hemagglutinin Array assay stratified by vaccine history [ Time Frame: Day 28 ]
  80. Specificity of the serum antibody response by Hemagglutinin Array assay stratified by vaccine history [ Time Frame: Day 7 ]
  81. Specificity of the serum antibody response by MN overall [ Time Frame: Day 28 ]
  82. Specificity of the serum antibody response by MN overall [ Time Frame: Day 7 ]
  83. Specificity of the serum antibody response by MN stratified by age group [ Time Frame: Day 28 ]
  84. Specificity of the serum antibody response by MN stratified by age group [ Time Frame: Day 7 ]
  85. Specificity of the serum antibody response by MN stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  86. Specificity of the serum antibody response by MN stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  87. Specificity of the serum antibody response by MN stratified by vaccine history [ Time Frame: Day 28 ]
  88. Specificity of the serum antibody response by MN stratified by vaccine history [ Time Frame: Day 7 ]
  89. Specificity of the serum antibody response by SPR overall [ Time Frame: Day 28 ]
  90. Specificity of the serum antibody response by SPR overall [ Time Frame: Day 7 ]
  91. Specificity of the serum antibody response by SPR stratified by age group [ Time Frame: Day 28 ]
  92. Specificity of the serum antibody response by SPR stratified by age group [ Time Frame: Day 7 ]
  93. Specificity of the serum antibody response by SPR stratified by baseline serum antibody level [ Time Frame: Day 28 ]
  94. Specificity of the serum antibody response by SPR stratified by baseline serum antibody level [ Time Frame: Day 7 ]
  95. Specificity of the serum antibody response by SPR stratified by vaccine history [ Time Frame: Day 28 ]
  96. Specificity of the serum antibody response by SPR stratified by vaccine history [ Time Frame: Day 7 ]

Secondary Outcome Measures :
  1. Serum antibody response by GFPDL overall [ Time Frame: Day 90 ]
  2. Serum antibody response by GFPDL stratified by acute antibody response [ Time Frame: Day 90 ]
  3. Serum antibody response by HAI overall [ Time Frame: Day 90 ]
  4. Serum antibody response by HAI stratified by acute antibody response [ Time Frame: Day 90 ]
  5. Serum antibody response by Hemagglutinin Array overall [ Time Frame: Day 90 ]
  6. Serum antibody response by Hemagglutinin Array stratified by acute antibody response [ Time Frame: Day 90 ]
  7. Serum antibody response by MN overall [ Time Frame: Day 90 ]
  8. Serum antibody response by MN stratified by acute antibody response [ Time Frame: Day 90 ]
  9. Serum antibody response by SPR overall [ Time Frame: Day 90 ]
  10. Serum antibody response by SPR stratified by acute antibody response [ Time Frame: Day 90 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   9 Years to 99 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Aged equal to or greater than 9 years of age and weigh at least 50 pounds.
  2. The subject must be in good health, as determined by: medical history; and targeted physical examination, when necessary, based on medical history. Stable medical or psychiatric condition is defined as: no recent increase in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months.
  3. The subject is able to understand and comply with the planned study procedures, including being available for all study visits.
  4. The subject/parent has provided informed consent/assent prior to any study procedures.
  5. Subjects who have not received seasonal flu vaccine for the current year.

Exclusion Criteria:

  1. Subject report of known hypersensitivity to allergy to components of the study vaccine or other components of the study vaccine.
  2. Subject report of known latex allergy
  3. Subject report of a history of severe reactions following previous immunization with licensed or unlicensed influenza virus vaccines.
  4. Subject report of a history of Guillain-Barre syndrome within 6 weeks of receipt of a previous influenza vaccine.
  5. The subject is a female of childbearing potential who is currently pregnant or breastfeeding or intends to become pregnant during the study period between enrollment and 90 days following receipt of vaccine. Pregnancy will be determined by subject interview. Pregnancy testing is not done in this study since there is no increased risk in pregnancy.
  6. The subject is immunosuppressed as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months.
  7. The subject has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematological malignancy. For this criterion, "active" is defined as having received treatment within the past 5 years.
  8. Have taken high-dose inhaled corticosteroids within 30 days prior to study vaccination. High-dose defined as per age as using inhaled high dose per reference chart https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/quick-reference-html#estimated-comparative-daily-doses
  9. The subject received immunoglobulin or another blood product within the 3 months prior to enrollment in this study.
  10. The subject has received an inactivated vaccine within the 2 weeks or a live vaccine within the 4 weeks prior to enrollment in this study or plans to receive another vaccine within the next 28 days after vaccination.
  11. The subject has an acute or chronic medical condition that, in the opinion of the investigator or appropriate sub-investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include any acute or chronic medical disease or conditions defined as persisting for 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 of the subject's successful completion of the study.
  12. Subjects with an active infection or that has an acute illness or an oral temperature greater than 99.9F (37.7C) within 3 days prior to enrollment or vaccination. Subjects who had an acute illness that was treated symptoms resolved are eligible to enroll as long as treatment is completed and symptoms resolved > 3 days prior to enrollment.
  13. The subject is currently participating or plans to participate in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study, or intends to donate blood during the study period.
  14. The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
  15. The subject has a history of alcohol or drug abuse in the 5 years prior to enrollment.
  16. The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C infection.
  17. Subject weighs less than 50 lbs.
  18. Subject expects to have a medical procedure during the upcoming 8 weeks that estimates blood loss to exceed 400 cc for adults or for children would exceed 3 ml/kg.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03328325


Contacts
Contact: Angela R. Branche 15852734104 angela_branche@urmc.rochester.edu

Locations
United States, New York
University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases Recruiting
Rochester, New York, United States, 14642-0001
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03328325     History of Changes
Other Study ID Numbers: 16-0101
HHSN272201400005C
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: December 14, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Influenza
PCR
Seasonal Vaccination

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs