Immunogenicity and Reactogenicity of an Inactivated Quadrivalent Influenza Vaccine Administered Intramuscularly to Children 6 to 35 Months of Age in 2012-2013: A Randomized, Double-Blind, Controlled, Multicenter, Multicountry, Clinical Trial

Joanne M Langley, Long Wang, Naresh Aggarwal, Agustin Bueso, Vijayalakshmi Chandrasekaran, Luis Cousin, Scott A Halperin, Ping Li, Aixue Liu, Shelly McNeil, Lourdes Peña Mendez, Luis Rivera, Bruce L Innis, Varsha K Jain, Joanne M Langley, Long Wang, Naresh Aggarwal, Agustin Bueso, Vijayalakshmi Chandrasekaran, Luis Cousin, Scott A Halperin, Ping Li, Aixue Liu, Shelly McNeil, Lourdes Peña Mendez, Luis Rivera, Bruce L Innis, Varsha K Jain

Abstract

Background: Influenza attack rates are high in 6- to 35-month-old children; vaccines containing both lineages of influenza B (Yamagata and Victoria), in addition to the H3N2 and H1N1 antigens, may improve protection rates.

Methods: In a randomized double-blind controlled trial, the immunogenicity and reactogenicity of an inactivated quadrivalent influenza vaccine (QIV) and a trivalent control vaccine (TIV) were assessed.

Results: Six hundred one children (QIV, n = 299; TIV, n = 302) were enrolled at 8 sites in 3 countries. The primary immunogenicity objective was met: the lower limit (LL) of the 2-sided 95% confidence interval (CI) for the seroconversion rate in QIV recipients ranged from 66.6% to 81.3%, which was ≥40% against all 4 strains. The immunogenic superiority of the additional B/Victoria strain in the QIV compared to that in the TIV was confirmed: the LL of the 2-sided 95% CI of the geometric mean titer ratio (QIV/TIV) (6.28 [95% CI, 5.32-7.41]) was greater than 1.5, and the LL of the 2-sided 95% CI for the difference in the seroconversion rate (QIV - TIV) (64.19% [95% CI, 57.65%-69.95%]) was greater than 10%. Injection-site pain and irritability/fussiness were the most commonly reported solicited injection-site and general adverse events, respectively, from days 0 to 6 and were similar in frequency between the groups.

Conclusions: In children aged 6 to 35 months, a QIV has superior immunogenicity for the added B strain and acceptable immunogenicity for shared strains, with no notable difference in reactogenicity and safety when compared to a TIV.

Keywords: children; immunogenicity; influenza vaccine.

Figures

Figure 1.
Figure 1.
Participant flow. Abbreviations: QIV, quadrivalent influenza vaccine; TIV-YB, trivalent influenza vaccine containing Yamagata lineage of the B strain.
Figure 2.
Figure 2.
SCRs for HI antibodies 28 days after the last vaccine dose (28 days after dose 1 [day 28] for primed subjects; 28 days after dose 2 [day 56] for unprimed subjects) in the ATP cohort for immunogenicity. The SCR was defined as an antibody titer of ≥40 1/DIL after vaccination for initially seronegative subjects and an antibody titer after vaccination of ≥4-fold the prevaccination antibody titer for initially seropositive subjects. % indicates the percentage of seroconverted subjects; error bars indicate 95% CIs. Abbreviations: Q-QIV, quadrivalent influenza vaccine; Q, manufactured in Quebec; TIV-YB, trivalent influenza vaccine containing Yamagata lineage of B strain; D, manufactured in Dresden.
Figure 3.
Figure 3.
Immunogenic superiority of QIV versus TIV-YB for the B Victoria strain in the ATP cohort for immunogenicity. Adjusted GMT indicates GMT adjusted for baseline titer; SCRs, an antibody titer of ≥40 1/DIL after vaccination for initially seronegative subjects and an antibody titer after vaccination of ≥4-fold the prevaccination antibody titer for initially seropositive subjects. Criteria for superiority were that the LL of the 2-sided 95% CI of the GMT ratio (Q-QIV /D-TIV-YB) was >1.5 and the LL of the 2-sided 95% CI on the SCR difference (Q-QIV – D-TIV-YB) was >10%. Error bars indicate 95% CIs.
Figure 4.
Figure 4.
Incidence and nature of local injection-site adverse events on days 0 to 6 after each vaccine dose in the TVC. Grade 3 pain was defined as a child crying when his or her limb was moved and/or spontaneously painful; grade 3, redness/swelling of >100 mm. Error bars indicate 95% CIs.
Figure 5.
Figure 5.
Incidence and nature of systemic adverse events on days 0 to 6 after each vaccine dose in the TVC. Grade 3 drowsiness was defined as drowsiness that prevented normal activity; grade 3 irritability/fussiness (irritability/fuss), crying that could not be comforted and/or prevented normal activity; grade 3 loss of appetite, child did not eat at all; grade 3 fever (or higher), temperature of ≥39.0°C (grade 4 fever also included here). Error bars indicate 95% CIs.

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Source: PubMed

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