TITRE III: Influenza B Immunogenicity Investigation

Study Overview
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Brief Summary
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Each winter, viruses belonging to two kinds of influenza A (A/H1N1 & A/H3N2) and two kinds of influenza B (B/Yamagata & B/Victoria) can cause illness. Historically, the yearly influenza vaccine that was recommended in children was designed to protect against both kinds of influenza A but only one kind of influenza B. In a series of trials conducted between 2008-09 and 2010-11 (TITRE I, II, and IIB), the TITRE investigators measured antibody response to influenza B in children who were primed with two doses of trivalent inactivated influenza vaccine (TIV) containing B/Yamagata. Overall, the investigators found that 2 doses of vaccine containing B/Yamagata did not adequately prime children for response to the alternate B/Victoria antigen and that subsequent vaccine doses containing B/Victoria-lineage antigen strongly boosted antibodies to the B/Yamagata antigen that was introduced during first immunization priming, but with lower responses to B/Victoria. For the first time since 2009-10, the recommended B/Victoria component of the seasonal influenza vaccine has been changed, from B/Brisbane/60/2008 to B/Colorado/60/2007 for the coming 2018-19 season. The investigators thus have a unique opportunity to clarify lineage-specific influenza B responses in a well-characterized cohort of children originally primed to Yamagata. The investigators' main interest is to assess whether TITRE I children primed with two doses of B/Yamagata in 2008-09 have since or are now capable of achieving a sufficient antibody response to B/Victoria following a single dose of 2018-19 QIV, ten years after their initial TIV B/Yamagata priming exposure.

Official Title
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TITRE III: TIV Infant/Toddler Response Evaluation - Influenza B Immunogenicity Investigation

Conditions
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Influenza

Intervention / Treatment
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* Biological: 2018-19 quadrivalent inactivated influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Child previously completed the TITRE I study in British Columbia or Quebec; Child is healthy (stable chronic conditions acceptable) as established by health assessment interview and verbal history-directed health examination; Child is available and can complete all relevant procedures during the study period; Parent or legal guardian is available and can be reached by phone during the study period; Parent/guardian provides written informed consent; Parent/guardian is fluent in English/French Exclusion Criteria: Child has already received the 2018-19 seasonal (TIV or QIV) influenza vaccine; Child has a bleeding condition that would prevent vaccine injection or blood collection; Child has known or suspected immunodeficiency; Child has a suspected or known anaphylactic reaction to any of the vaccine components used in this study; Child has a health condition which, in the opinion of the investigator, would interfere with the evaluation or pose a health risk to the child; Child has received immune globulin or other blood products within the prior six weeks; Child has received injected or oral steroids within the prior six weeks defined by more than 1 week of immunosuppressants or immune modifying drugs (e.g. oral prednisolone >0.5mL/kg/day or intravenous glucocorticoid steroid). Nasal, topical or inhaled steroids are allowed; Child has received any live vaccine within 28 days of the study vaccine or is scheduled to receive live vaccine during the study period; Child has received any inactivated vaccine within 14 days of the study vaccine; Child is or will be enrolled in any other clinical trial of a drug, vaccine or medical device during the study period.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: influenza vaccine recipients<br>Participants of an earlier clinical trial (TITRE I) to receive one dose of the 2018-19 quadrivalent inactivated influenza vaccine | Biological: 2018-19 quadrivalent inactivated influenza vaccine<br>* A single age-appropriate dose of 2018-19 quadrivalent inactivated influenza vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection rate (SPR) for B/Victoria vaccine strains | SPR based on hemagglutination inhibition (HI) assay for current (B/Colorado/06/2017-like) and prior (B/Brisbane/60/2008-like) Victoria lineage vaccine strains | Pre-vaccination | 
| Seroprotection rate (SPR) for B/Victoria vaccine strains | SPR based on hemagglutination inhibition (HI) assay for current (B/Colorado/06/2017-like) and prior (B/Brisbane/60/2008-like) Victoria lineage vaccine strains | 4-6 weeks after receipt of QIV | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titre (GMT) for B/Victoria vaccine strains |  | Pre-vaccination | 
| Geometric mean titre (GMT) for B/Victoria vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Geometric mean titre ratio (GMTR) for B/Victoria vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Seroconversion rate (SCR) for B/Victoria vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Seroprotection rate (SPR) for B/Yamagata vaccine strains |  | Pre-vaccination | 
| Seroprotection rate (SPR) for B/Yamagata vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Geometric mean titre (GMT) for B/Yamagata vaccine strains |  | Pre-vaccination | 
| Geometric mean titre (GMT) for B/Yamagata vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Geometric mean titre ratio (GMTR) for B/Yamagata vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Seroconversion rate (SCR) for B/Yamagata vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Seroprotection rate (SPR) for A/H1N1 vaccine strains |  | Pre-vaccination | 
| Seroprotection rate (SPR) for A/H1N1 vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Geometric mean titre (GMT) for A/H1N1 vaccine strains |  | Pre-vaccination | 
| Geometric mean titre (GMT) for A/H1N1 vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Geometric mean titre ratio (GMTR) for A/H1N1 vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Seroconversion rate (SCR) for A/H1N1 vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Seroprotection rate (SPR) for A/H3N2 vaccine strains |  | Pre-vaccination | 
| Seroprotection rate (SPR) for A/H3N2 vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Geometric mean titre (GMT) for A/H3N2 vaccine strains |  | Pre-vaccination | 
| Geometric mean titre (GMT) for A/H3N2 vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Geometric mean titre ratio (GMTR) for A/H3N2 vaccine strains |  | 4-6 weeks after receipt of QIV | 
| Seroconversion rate (SCR) for A/H3N2 vaccine strains |  | 4-6 weeks after receipt of QIV |