Cell Culture-derived Influenza Vaccine Research Articles

Subunit Influenza Vaccines Produced from Cell Culture or in Embryonated Chicken Eggs: Comparison of Safety, Reactogenicity, and Immunogenicity

This study assessed the safety, reactogenicity, and immunogenicity of an injectable cell culture-derived influenza vaccine (CCIV), compared with those of an injectable egg-based trivalent inactivated influenza vaccine (TIV). Adult subjects (n = 613; 18 to <50 years of age) were randomized (1:1) to receive either CCIV or TIV. The safety and reactogenicity of the 2 vaccines were assessed on the basis of solicited indicators and other adverse events (AEs) within 7 days of vaccination. All serious AEs and those AEs resulting in withdrawal were recorded throughout the study. Antibody titers were determined by the hemagglutination inhibition assay, using egg- and cell-derived antigens. Immunogenicity was assessed on the basis of the ratio of postvaccination (day 22) geometric mean titers (GMTs) between the 2 vaccines, seroprotection rates, and seroconversion rates. There was no clinically relevant difference between the safety and reactogenicity profiles of the 2 vaccines. The immunogenicity of CCIV was demonstrated to be noninferior to that of TIV on the basis of the ratio of postvaccination GMTs between the 2 vaccines. GMTs, seroprotection rates, and seroconversion rates were comparable between the 2 vaccines. The safety, reactogenicity, and immunogenicity of the CCIV and the egg-based TIV are comparable.

A novel mammalian cell-culture technique for consistent production of a well-tolerated and immunogenic trivalent subunit influenza vaccine

Conventional influenza vaccine production methods have limitations due to their reliance on chicken eggs. We evaluated whether a mammalian cell-culture system could reliably produce an influenza vaccine with favourable tolerability and immunogenicity profiles. Adult subjects ( n = 1200; 18–60 years of age) were randomized (2:2:2:1) to receive either one of three lots of a cell-culture-derived influenza vaccine (CCIV) or an egg-based trivalent inactivated influenza vaccine (TIV). Safety and reactogenicity were assessed using solicited indicators for 7 days post-vaccination, all other adverse events (AEs) were recorded for 21 days post-vaccination, and all serious AEs and AEs necessitating a physician's visit, and/or resulting in subject's withdrawal from the study, were collected for up to 6 months post-vaccination. Antibody titres were measured by haemagglutination inhibition (HI) assay using egg-based viral antigens. All three lots of CCIV had similar safety and tolerability profiles, analogous to those of the TIV. Lot-to-lot consistency was statistically demonstrated through bioequivalence for immunogenicity. Antibody titres assessed at 6 months demonstrated good persistence. This Phase III trial is the first to demonstrate lot-to-lot bioequivalence of a CCIV and persistence of immunogenicity in comparison with a TIV.

Trivalent MDCK cell culture-derived influenza vaccine Optaflu® (Novartis Vaccines)

Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu®, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.

A New Mammalian Cell Culture-Derived Influenza Vaccine is as Safe as, and Immunogenically Non-Inferior to, an Egg-Based Influenza Vaccine

A New Mammalian Cell Culture-Derived Influenza Vaccine is as Safe as, and Immunogenically Non-Inferior to, an Egg-Based Influenza Vaccine

Safety, tolerability and immunogenicity of a mammalian cell-culture-derived influenza vaccine: A sequential Phase I and Phase II clinical trial

This sequential, observer-blind, randomised, single-centre, combined Phase I and Phase II clinical trial compared the tolerability and immunogenicity of a single intramuscular dose of a novel cell-culture-derived influenza vaccine (CCIV), produced in Madin–Darby canine kidney cells, with a conventional egg-based vaccine. The immunogenicity of both vaccines was assessed by SRH assay, a well-recognized test by EMEA, in compliance with the requirements of the EU Committee for Medicinal Products for Human Use (CHMP). The Phase I part of the trial comprised 40 healthy adults (18–40 years of age); the subsequent Phase II part involved 200 healthy adult ( n = 80, 18–60 years of age) and elderly ( n = 120, ≥61 years of age) subjects. Both vaccines showed similar reactogenicity and any solicited local or systemic reactions were mostly mild or moderate. Regarding immunogenicity, both the CCIV and the control vaccine met all of the EU Committee for Medicinal Products for Human Use criteria for influenza vaccines for each strain and in both age groups. In conclusion, the CCIV produced in mammalian cell-culture is as well tolerated and as immunogenic as the control egg-based vaccine in non-elderly and elderly adults.

Head-to-head comparison of four nonadjuvanted inactivated cell culture-derived influenza vaccines: Effect of composition, spatial organization and immunization route on the immunogenicity in a murine challenge model

In order to study the influence of antigen composition, spatial organization of antigen and the route of administration, four cell culture-derived, inactivated, nonadjuvanted influenza vaccine formulations, i.e. whole inactivated virus (WIV), split, subunit and virosome vaccines were prepared from a single antigen batch. We directly compared the immunogenicity and efficacy of these vaccine formulations after intramuscular (i.m.) or intranasal (i.n.) administration in mice. Prime and boost vaccination were followed by a potentially lethal homologous aerosol challenge. For all vaccines, the i.m. route induced higher serum humoral immune responses as compared to the i.n. route and protected all mice against challenge at a dose of 5 μg. Upon i.n. immunization only WIV and split vaccines induced detectable IgG titers and partial protection against challenge but only very low HI titers were induced in almost all mice. WIV induced mainly IgG2a/c titers via both routes, whereas split vaccine induced exclusively IgG1 titers via both routes. Subunit and virosome vaccines induced exclusively IgG1 via the i.m. route. Mucosal sIgA levels were only detected after i.n. vaccination with WIV. Furthermore, vaccines containing all viral components (WIV and split vaccine) induced higher serum HI titers and serum antibody titers than subunit and virosome vaccines. The differences in magnitude and quality of immune responses of split and WIV, having the same composition, are likely related to their distinct spatial organization. In conclusion, the direct comparison between WIV, split, subunit and virosomes, shows that the differences in immune responses between these well known influenza vaccines can be explained by both the composition and particulate structure of these vaccine formulations.

Safety and immunogenicity of a trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children

We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19–50 years), children (3–12 years) and the elderly (≥65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults ( n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors ( n=269), and one lot of each vaccine in children ( n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors.