Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults

Abstract

BackgroundGSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children.MethodsThe Phase III, randomized, double-blind, multinational study included three cohorts: adults (18–49 years; N = 120), children (3–17 years; N = 821), and infants (6–35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 μg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine.ResultsThe primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786).ConclusionsThe study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process.Trial registrationClinicalTrials.gov: NCT02207413; trial registration date: August 4, 2014.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3079-8) contains supplementary material, which is available to authorized users.

Safety Profile of GSK’s Inactivated Quadrivalent Seasonal Influenza Vaccine in Belgium, Germany and Spain: Passive Enhanced Safety Surveillance Study for the 2019/2020 Influenza Season

“…The frequency of reported fever in children aged 6 months–8 years in this current passive ESS study was comparable to that reported in clinical trials [ 21 , 23 ]. However, it should be cautiously interpreted since the fever ≥ 38 °C was self-reported by parents in the current study, and we did not have the chance to assess the start and end date of fever during the first 7 days post vaccination.…”

A Single Dose of Inactivated Influenza Virus Vaccine Expressing COBRA Hemagglutinin Elicits Broadly-Reactive and Long-Lasting Protection

“…The SIV vaccines with improved safety has been used as a commercial seasonal influenza virus vaccine for decades and is safe and effective in most populations (18). However, the SIV vaccine is not as effective in children and the elderly (21,37,38). The reduced vaccine effectiveness elicited by SIV vaccines compared to WIV vaccines was also observed in this study.…”

Pandemic influenza virus vaccines boost hemagglutinin stalk-specific antibody responses in primed adult and pediatric cohorts

“…The clinical trials included [25][26][27][28][29][30][31][32] and the number of participants is shown in Table 1. Demographic characteristics and prevaccination seropositivity for HI against the vaccine homologous virus and the A/H1N1pdm09 virus are shown in Supplementary Tables 1 and 2, respectively. ELISA Anti-H1 stalk antibodies.…”

“…6; Table 1; Supplementary Table 6). [25][26][27][28][29][30][31][32] We aimed to select approximately 30 participants from the relevant treatment groups of each trial. Participants were eligible for the present study if they had completed the clinical trial according to the protocol and had sufficient residual sample volume at all protocol-specified sample timepoints.…”