Immunogenicity and Protective Efficacy in Mice of Influenza B Virus Vaccines Grown in Mammalian Cells or Embryonated Chicken Eggs

Abstract

The immunogenicity and protective efficacy of formalin-inactivated influenza B/Memphis/1/93 virus vaccines propagated exclusively in Vero cells, MDCK cells, or embryonated chicken eggs (hereafter referred to as eggs) were investigated. Mammalian cell-grown viruses differ from the egg-grown variant at amino acid position 198 (Pro/Thr) in the hemagglutinin gene. The level of neuraminidase activity was highest in egg-grown virus, while MDCK and Vero cell-derived viruses possessed 70 and 90% less activity, respectively. After boosting, each of the vaccines induced high levels of hemagglutinin-inhibiting, neuraminidase-inhibiting, and neutralizing antibodies that provided complete protection from MDCK-grown virus challenge. Mammalian cell-derived virus vaccines induced serum antibodies that were more cross-reactive, while those induced by egg-grown virus vaccines were more specific to the homologous antigen. Enzyme-linked immunospot analysis indicated that cell-grown virus vaccines induced high frequencies of immunoglobulin G (IgG)-producing cells directed against both cell- and egg-grown virus antigens, whereas egg-grown virus vaccine induced higher frequencies of IgG- and IgM-producing cells reacting with homologous antigen and low levels of IgG-producing cells reactive with cell-grown viruses. These studies indicate that influenza B virus variants selected in different host systems can elicit different immune responses, but these alterations had no detectable influence on the protective efficacy of the vaccines with the immunization protocol used in this study.

Generation of candidate human influenza vaccine strains in cell culture – rehearsing the European response to an H7N1 pandemic threat

“…being ordered in advance or to an avian outbreak reducing the supply of eggs. In addition, it has been shown in animal studies that vaccines produced in mammalian tissue culture can be more protective than those grown in eggs, [44][45][46] an advantage in a pandemic situation. Further studies are required to determine whether this is the case for the RD3 vaccine.…”

Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination

“…There are few alternative models in mice and ferrets (McLaren, Potter et al 1974;Alymova, Kodihalli et al 1998), but better models are required since anatomical and physiological relevance are as important as immunological relevance. Rabbits, non-human primates and pigs are considered anatomically and physiologically relevant (Ivins, Pitt et al 1998;Macklin, McCabe et al 1998;Little, Ivins et al 2006), but their use in influenza challenge studies is as yet unproven.…”

Expression and purification of an influenza hemagglutinin—one step closer to a recombinant protein-based influenza vaccine

“…The cell culture-based approach involves production of influenza viruses in cell culture followed by the current (egg-based) virus inactivation and purification for the down stream processing. The advantages are: cell cultures are easier to handle and can be scaled up in a short period of time, and the influenza vaccines produced with this approach have been tested in Phase I and Phase II clinical trials and were found to be safe and at least as effective as the vaccines produced in embryonated chicken eggs [13][14][15]. A limitation of the cell culture-based approach is that the process still requires the production of a high-yielding re-assorted virus.…”