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BMC Infect Dis. 2018 Apr 18;18(1):186. doi: 10.1186/s12879-018-3079-8.

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.

Author information

1
GSK, Clinical Research and Development, Wavre, Belgium. carine.x.claeys@gsk.com.
2
GSK, Clinical Evidence Generation (CEG), King of Prussia, PA, USA.
3
Hospital Universitario HM Sanchinarro, Clinical Investigation in Vaccines Unit, Madrid, Spain.
4
icddr,b, MCHD Administration, Dhaka, Bangladesh.
5
Instituto Hispalense de Pediatría, Pediatría, Sevilla, Spain.
6
Cabinet Médical Tran, Pédiatrie, Nice, France.
7
Antequera Hospital, UGC de Pediatría, Málaga, Spain.
8
Department of Pediatrics, Santiago de Compostela, Hospital Clínico Universitario de Santiago, Translational Pediatrics and Infectious Diseases, Galicia, Spain.
9
Instituto de Investigación Sanitaria de Santiago and Universidade de Santiago de Compostela (USC), Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría (GENVIP), Galicia, Spain.
10
Association Française de Pédiatrie Ambulatoire (AFPA), Pédiatrie, Essey-les-Nancy, France.
11
Dr. med. Michael R. Horn Office, Pediatrics, Schoenau am Koenigssee, Germany.
12
Klinikum Würzburg Mitte, Standort Juliusspital, Central Laboratory and Vaccination Centre, Würzburg, Germany.
13
Ulrich Behre, Practice, Kehl, Germany.
14
Pediatric Department, Hospital Universitario de Burgos, Burgos, Spain.
15
Department of Obstetrics and Gynecology, Faculty of Medicine, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Torun, Poland.
16
Department of Neonatology, University Hospital No 2, Bydgoszcz, Poland.
17
NZOZ, Praktyka Lekarza, Oborniki Śląskie, Poland.
18
GSK, Global Industrial Operations, Dresden, Germany.
19
Present Address: Pfizer VRD, Collegeville, PA, USA.
20
GSK, Clinical Research and Development, King of Prussia, PA, USA.
21
Present Address: Bill and Melinda Gates Foundation, Seattle, WA, USA.
22
Present Address: PATH, Washington, DC, USA.

Abstract

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.

KEYWORDS:

Adults; Children; Immunogenicity; Infants; Influenza vaccine; Investigational; Manufacturing; Quadrivalent; Reactogenicity; Safety

PMID:
29669531
PMCID:
PMC5907359
DOI:
10.1186/s12879-018-3079-8
[Indexed for MEDLINE]
Free PMC Article

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