Microcarrier / CEF / Media SYSTEM to make Viral Vaccines
DESCRIPTION (Provided by Applicant): This research plan is to develop a
Microcarrier-Bioreactor Cell Culture System for the growth and efficient
recovery of infected, whole cells from microcarriers in controlled, bioreactor
cultures. Primary chick embryo fibroblast (CEF) cells are widely used in viral
vaccine production (for both avian and human vaccines), but there are no known
licensed-manufacturing protocols which utilize a Microcarrier-Bioreactor System
for this purpose. Focus will be on the production of a whole cell Marek's
Disease vaccine for avian applications. The System technology developed in the
course of these studies could replace large-scale industrial processes in which
(1) primary CEF cells are utilized in roller bottles, (2) embryonated, fertile
eggs function as tiny bioreactors, such as in the manufacturing of human
influenza vaccine or (3) whole cell vaccines and/or immunotherapies.
Specific Aims I, II and VI. To optimize cell culture conditions for a one to
two day HVT-production run using primary CEF cells, secondary CEF cells and
immortalized CEF-like cells at high density, in a one-liter bioreactor culture.
Specific Aim III. To optimize culture conditions for a three-day HVT-production
run using secondary CEF cells at the one-liter scale in bioreactor culture.
Specific Aim IV & V. To develop protocols for rapid harvesting of HVT-infected
cells, and separation of those cells from microcarriers, and to achieve
high-titer Marek's vaccine production.
PROPOSED COMMERCIAL APPLICATION:
Many animal vital vaccines (e.g. Marek's) and human viral vaccines are produced
using chick embryo cells, either in roller bottle systems or in embryonated chicken
eggs. Neither process uses microcarrier - bioreactor systems. Large scale
production of Marek's vaccine in a Miaocarrier-Bioreactor System, will lead to
substantial economic advantages when bioreactors are compared to old technology.
Product quality and consistency should also be improved. and manufacturing costs
reduced. The System herein proposed will utilize (1) primary or secondary CEF
cells, or immortalized cell lines. (2) special media formulations, (3) bovine sera
and will evolve the (4) protocols to produce vaccines in this System. The
technology should extrapolate to other whole-cell human vaccines.
PROPOSED COMMERCIAL APPLICATION:
The current short supply of human influenza vaccine serves to underline the
importance for developing technology that is an alternative to embryonated egg
production methods. The lead time from (1) a CDC estimate of the specific influenza
virus variant likely to strike the USA, to (2) the availability of the vaccine on a large
scale is exceedingly long, many months. In the event of an influenza pandemic
this many-month lead-time could result in a high fatality rate reminiscent of the
1917-18 pandemic. If influenza virus vaccine can be produced in very large-scale
bioreactors, with a fast turn around time (a couple months), the high fatality rate of
a pandemic might be averted. The research proposed has the potential to address
Small Business Information at Submission:
Principal Investigator:William J. Hillegas
SOLOHILL ENGINEERING, INC.
4220 VARSITY DR ANN ARBOR, MI 48108
Number of Employees: