Development of an influenza virus vaccine using the baculovirus-insect cell expression system : implications for pandemic preparedness

M.M.J. Cox

Research output: Thesisinternal PhD, WU

Abstract

Key word

Influenza, rHA, vaccine, baculovirus, insect cells, production, pandemic preparedness

Influenza (or flu) is a highly contagious, acute viral respiratory disease that occurs seasonally in most parts of the world and is caused by influenza viruses. Influenza vaccination is an effective way to reduce the complications and the mortality rate following influenza infections. The currently available influenza vaccines are manufactured in embryonated chicken eggs, a 40-year old production technology. The research in this thesis was aimed at the design, validation and development of a production process for a recombinant hemagglutinin (rHA) influenza vaccine for the prevention of seasonal influenza. The viral surface protein HA is the key antigen in the host response to influenza virus since neutralizing antibodies directed against HA can mitigate or prevent infection. The baculovirus-insect cell system was selected for the synthesis of rHA molecules. The designed process was used to manufacture candidate trivalent rHA vaccines, which were tested in four clinical studies in a total of more than 3000 human subjects age 18 - 92 to support licensure of FluBlok under the “Accelerated Approval” procedure in the United States (U.S.). These studies demonstrated that the purified rHA protein was well tolerated and resulted in a strong and long lasting immune response. In addition, the novel vaccine provided cross protection against drifted influenza viruses. In response to the emergence of the new H1N1 A/California /04/2009 influenza strain, the outlined design was used to produce a rHA vaccine candidate and merely 6 weeks later, the first batches of vaccine were ready for human clinical testing. There are two especially important advantages to the use of this technology from a public health perspective: First, the insect cell-baculovirus system has demonstrated the potential to facilitate safe and expeditious responses to health care emergencies such as the one currently posed by the novel H1N1 virus pandemic and secondly, the rHA vaccine does not contain ovalbumin or other antigenic proteins that are present in eggs and may therefore be administered to people who are egg-allergic.


Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Vlak, Just, Promotor
  • van Oers, Monique, Co-promotor
Award date9 Dec 2009
Place of Publication[S.l.
Publisher
Print ISBNs9789085854791
Publication statusPublished - 2009

Keywords

  • vaccine development
  • vaccines
  • influenza
  • baculovirus
  • insects
  • haemagglutinins
  • cell culture vaccines
  • recombinant vaccines

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