Immunogenicity and Safety of an EB66 Cell-Culture-Derived Influenza A/Indonesia/5/2005(H5N1) AS03-Adjuvanted Vaccine: A Phase 1 Randomized Trial

Anne Schuind, Nathan Segall, Mamadou Drame, Bruce L Innis, Anne Schuind, Nathan Segall, Mamadou Drame, Bruce L Innis

Abstract

Background: Cell-culture-derived (CC) influenza vaccine production methods could provide benefits over classical embryonated-egg technology, including a higher production capacity and the faster creation of a supply that meets demand.

Methods: A CC-inactivated split-virus influenza A/Indonesia/5/2005(H5N1) vaccine derived from the EB66 cell line (hereafter, "CC-H5N1") was investigated in a phase 1 randomized, blinded study. Healthy adults (n = 521) received 2 vaccine doses (days 0 and 21) of either investigational CC-H5N1 vaccine (1.9 µg or 3.75 µg of hemagglutinin antigen [HA] with the AS03 adjuvant system or 15 µg of plain HA), embryonated-egg-derived vaccines (3.75 µg of HA with AS03 or 15 µg of plain HA), or placebo. Assessment of the adjuvant effect and immunogenicity was performed using Center for Biologics Evaluation and Research acceptability criteria 21 days after dose 2. Safety was assessed until month 12.

Results: AS03-adjuvanted CC-H5N1 elicited a homologous hemagglutination inhibition antibody response that satisfied immunogenicity criteria 21 days after dose 2 and persisted at month 12. Adjuvant effect and immune response against a drift-variant strain were demonstrated. No vaccine-related serious adverse events were reported. The immunogenicity and safety of the CC-H5N1 formulation containing 3.75 µg of HA and AS03 appeared to be similar to those for the licensed egg-derived AS03-adjuvanted control vaccine.

Conclusions: The feasibility of the EB66 cell line to produce an immunogenic influenza vaccine with acceptable safety profile was demonstrated. Antigen sparing was achieved through combination with AS03 adjuvant. This CC-H5N1 might contribute to the rapid access of vaccine in the event of an influenza A(H5N1) pandemic.

Clinical trials registration: NCT01236040.

Keywords: AS03; cell culture; influenza A(H5N1); pandemic influenza vaccine.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Subject flow through the study. Subjects were eliminated at day 42 (D42) after the first dose for the following reasons (1 subject could have several elimination codes): protocol violation (n = 1), received protocol-forbidden medication (n = 1), underlying medical condition (n = 1), noncompliance with vaccination or blood sampling schedule (n = 11), and invalid results or insufficient serum quantity (n = 8). Subjects were eliminated at month 12 (M12) after the first dose for the following reasons (1 subject could have several elimination codes): protocol violation (n = 1), received protocol-forbidden medication (n = 2), underlying medical condition (n = 1), noncompliance with vaccination or blood sampling schedule (n = 5), invalid results or insufficient serum quantity (n = 3), and incomplete vaccination schedule and eliminated from the D42 analysis (n = 7). CC-1.9 µgHA + AS03B, cell-culture-derived formulation with 1.9 µg of HA plus AS03B adjuvant; CC-3.75 µgHA + AS03A, cell-culture-derived formulation with 3.75 µg of HA plus AS03A adjuvant; CC-15 µgPlainHA, cell-culture-derived formulation with 15 µg of HA without adjuvant; HA, hemagglutinin antigen; PP, per protocol; Q-3.75 µgHA + AS03A, egg-derived formulation with 3.75 µg of HA plus AS03A adjuvant; Q-15 µgPlainHA, egg-derived formulation with 15 µg of HA without adjuvant.
Figure 2.
Figure 2.
Percentage of subjects reporting solicited injection site or general symptoms within 7 days of either vaccine dose—total vaccinated cohort. Vertical lines indicate 95% confidence intervals. Grade 3 is defined as redness and swelling (diameter, >100 mm), a temperature of ≥39.0°C (any route), and, for all other symptoms, as symptoms with sufficient severity to prevent normal activities (eg inability to attend work/school). CC-1.9 µgHA + AS03B, cell-culture-derived formulation with 1.9 µg of HA plus AS03B adjuvant; CC-3.75 µgHA + AS03A, cell-culture-derived formulation with 3.75 µg of HA plus AS03A adjuvant; CC-15 µgPlainHA, cell-culture-derived formulation with 15 µg of HA without adjuvant; HA, hemagglutinin antigen; Q-3.75 µgHA + AS03A, egg-derived formulation with 3.75 µg of HA plus AS03A adjuvant; Q-15 µgPlainHA, egg-derived formulation with 15 µg of HA without adjuvant.

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Source: PubMed

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