Dataset Information

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: a randomized, double-blind, controlled phase III clinical trial in children aged 6-35 months in China.

ABSTRACT: Mismatch between circulating influenza B viruses and vaccine strains occurs frequently. In a randomized, double-blind, controlled phase III clinical study, healthy children aged 6-35 months were randomized into three groups at a ratio of 2:1:1, received two doses of quadrivalent influenza vaccines (QIVs) or licensed trivalent influenza vaccines (TIVs). The primary objective was to evaluate the non-inferiority immunogenicity of QIV compared with the two TIVs, containing B/Victoria or B/Yamagata strain. Safety information was collected for 28 days after each vaccination. Serious adverse events (SAEs) were monitored for 6 months after the second vaccination. A total of 2146 subjects (QIV: 1069, TIV-Vic: 540, TIV-Yam: 537) were enrolled in this study. QIV was found non-inferior to TIVs for shared strains (A/H1N1 and A/H3N2) and corresponding BY strain based on hemagglutination inhibition (HI) antibodies 28 days after the second dose of vaccination. The resulted geometric mean titer (GMT) ratios (QIV/TIV) were 0.98 (0.89, 1.07) for H1N1, 0.95 (0.85, 1.05) for H3N2 and 0.89 (0.81, 0.98) for BY. And the seroconversion rate differences (QIV-TIV) were -0.46% (-3.24%, 2.31%) for H1N1, -1.95% (-5.54%, 1.65%) for H3N2 and -3.58% (-8.11%, 0.95%) for BY. The BV strain in QIV did not reach the non-inferiority criteria, with GMT of 1:52.25 (vs. 1:61.02 of TIV-Vic) and seroconversion rate of 59.49% (vs. 66.85% of TIV-Vic). No increased safety concerns occurred in QIV group. Candidate QIV can provide good protection for children aged 6 to 35 months, and its immunogenicity and safety were proved.

Clinical trials registration

ClinicalTrials.gov number: NCT03859141.

SUBMITTER: Hu Y

PROVIDER: S-EPMC7482894 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:GSK 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. METHODS:The 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. RESULTS:The 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). CONCLUSIONS:The 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 REGISTRATION:ClinicalTrials.gov: NCT02207413 ; trial registration date: August 4, 2014.

Project description:BackgroundTwo antigenically distinct influenza B lineages have co-circulated since the 1980s, yet inactivated trivalent influenza vaccines (TIVs) include strains of influenza A/H1N1, A/H3N2, and only one influenza B from either the Victoria or Yamagata lineage. This means that exposure to B-lineage viruses mismatched to the TIV is frequent, reducing vaccine protection. Formulations including both influenza B lineages could improve protection against circulating influenza B viruses. We assessed a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages versus TIV in adults in stable health.MethodsA total of 4659 adults were randomized 5:5:5:5:3 to receive one dose of QIV (one of three lots) or a TIV containing either a B/Victoria or B/Yamagata strain. Hemagglutination-inhibition assays were performed pre-vaccination and 21-days after vaccination. Lot-to-lot consistency of QIV was assessed based on geometric mean titers (GMT). For QIV versus TIV, non-inferiority against the three shared strains was demonstrated if the 95% confidence interval (CI) upper limit for the GMT ratio was ≤1.5 and for the seroconversion difference was ≤10.0%; superiority of QIV versus TIV for the alternate B lineage was demonstrated if the 95% CI lower limit for the GMT ratio was > 1.0 and for the seroconversion difference was > 0%. Reactogenicity and safety profile of each vaccine were assessed. Clinicaltrials.gov: NCT01204671.ResultsConsistent immunogenicity was demonstrated for the three QIV lots. QIV was non-inferior to TIV for the shared vaccine strains, and was superior for the added alternate-lineage B strains. QIV elicited robust immune responses against all four vaccine strains; the seroconversion rates were 77.5% (A/H1N1), 71.5% (A/H3N2), 58.1% (B/Victoria), and 61.7% (B/Yamagata). The reactogenicity and safety profile of QIV was consistent with TIV.ConclusionsQIV provided superior immunogenicity for the additional B strain compared with TIV, without interfering with antibody responses to the three shared antigens. The additional antigen did not appear to alter the safety profile of QIV compared with TIV. This suggests that the candidate QIV is a viable alternative to TIV for use in adults, and could potentially improve protection against influenza B.Trial registrationClinical Trials.gov: NCT01204671/114269.

Project description:The influenza B virus has two lineages; Yamagata and Victoria. The two lineages are antigenically distinct and it is difficult to expect cross-protection between the lineages. Actually, the mismatch between circulating influenza B viruses and vaccine strains has been occurred frequently. The cell-culture system for the production of influenza vaccine can contribute to improve vaccine strain selection and expand vaccine supplies. We investigated the immunogenicity and safety of cell culture-derived quadrivalent inactivated influenza vaccine (NBP607-QIV) in adults and elderly subjects.A randomized controlled phase III trial was undertaken in 10 university hospitals in the Republic of Korea (Clinical trial Number-NCT02467842). Adults (aged 19-59 years) and elderly subjects (aged ?60 years) were randomly assigned in a 2:1:1 ratio to NBP607-QIV versus cell culture-based trivalent inactivated influenza vaccine-Yamagata (NBP607-Y) and cell culture-based trivalent inactivated influenza vaccine-Victoria (NBP607-V). Immunogenicity was assessed 3 weeks after vaccination by hemagglutination inhibition assay. Safety was assessed for 6 months post-vaccination: solicited adverse events (AEs) for 7 days, unsolicited AEs for 21 days and serious adverse events (SAEs) for 6 months. AEs were sub-classified as adverse drug reactions (ADRs) according to the causality.A total of 1,503 participants were randomly assigned to NBP607-QIV (n = 752), NBP607-Y (n = 373) and NBP607-V (n = 378). The seroconversion rates of NBP607-QIV were 52.4%, 51.2%, 43.7% and 55.8% against A/H1N1, A/H3N2, B/Yamagata and B/Victoria, respectively. Non-inferiority against shared strains and superiority against alternate-lineage B strains were demonstrated for NBP607-QIV vs. NBP607-Y and NBP607-V. A total of 730 reactions occurred in 324 (43.1%) subjects of NBP607-QIV group. Majority of ADRs was solicited (99.2%) and mild (90.3%) in intensity. In adults (aged 19-59 years), solicited local AEs were slightly more frequent in NBP607-QIV group than NBP607-Y or NBP607-V group (40.9%, 33.4% and 32.5%, respectively). One SAE was observed among NBP607-QIV group, which was considered to be unrelated to the study vaccine within 3 weeks of vaccination and no vaccine-related SAEs were reported up to 6 months after vaccination.NBP607-QIV is a safe, well-tolerated and immunogenic influenza vaccine in Korean adults and elderly subjects.

Dataset Information

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: a randomized, double-blind, controlled phase III clinical trial in children aged 6-35 months in China.

Clinical trials registration

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets