PER.C6 Cell Line
'PER.C6 Cell line
The heart of the technology is the PER.C6 human cell line. This is a continuously dividing set of cells derived from a single human retina c'''''ell, immortalized using recombinant DNA technology. Like other continuous cell lines, PER.C6 cells can replicate indefinitely—but that is where the comparison ends.
PER.C6 Technology PER.C6 cells are created from retinal tissue of 18-week gestation aborted fetus
October 13, 2015 – Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell-based inactivated poliovirus vaccine “The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10–25 L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6® cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6® cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents.”
January 21, 2013 – PER.C6 cells as a serum-free suspension cell platform for the production of high titer poliovirus: A potential low cost of goods option for world supply of inactivated poliovirus vaccine “There are two highly efficacious poliovirus vaccines: Sabin’s live-attenuated oral polio vaccine (OPV) and Salk’s inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to virulent poliovirus strains which can result in Vaccine-Associated Paralytic Poliomyelitis (VAPP) in vaccinees. Furthermore, some OPV revertants with high transmissibility can circulate in the population as circulating Vaccine-Derived Polioviruses (cVDPVs). IPV does not convey VAPP and cVDPVs but the high costs per dose and insufficient supply have rendered IPV an unfavorable option for low and middle-income countries.”
February 2011- Development and strategies of cell-culture technology for influenza vaccine. Influenza is a pandemic contagious disease and causes human deaths and huge economic destruction of poultry in the world. In order to control and prevent influenza, mainly type A, influenza vaccine for human and poultry were available since the 1940s and 1920s, respectively. In the development of vaccine production, influenza viruses were cultured originally from chicken embryos to anchorage-dependent cell lines, such as MDCK and Vero. The anchorage-independent lines have also been used to produce influenza virus, such as PER.C6 and engineering modified MDCK and Vero. During the process of influenza vaccine production, the common problem faced by all producers is how to improve the titer of influenza virus. Comment: The purpose of creating cell lines for influenza vaccine production is that eggs are slow and only one “crop” per year can be produced. With cell lines, a batch of vaccine can be produced every 3-6 weeks.
April 2010 – Rapid generation of a well-matched vaccine seed from a modern influenza A virus primary isolate without recourse to eggs. Most influenza vaccines are produced in chicken eggs but recent human influenza strains often do not grow well in this substrate. The PER.C6 cell line is an alternative platform for vaccine production. Here we demonstrate that PER.C6 cells faithfully propagate recent clinical isolates, without selecting for mutations in the HA gene. PER.C6 cells support the rescue of recombinant influenza viruses from cDNA.
February 2010 – Developing cell culture-derived pandemic vaccines. This review introduces the concepts of modern, cell culture-derived influenza vaccines and their manufacture, and explains the advantages of these vaccines in terms of both speed and efficiency of production as well as immunogenic efficacy. Vaccine production technologies using the mammalian cell lines Vero, MDCK and PER.C6, as well as the baculovirus/insect cell platform, are described in detail.
December 2009 – Continuous cell lines as a production system for influenza vaccines. Conventionally, human influenza vaccines are produced in embryonated chicken eggs. Currently, vaccines produced in three different host cell lines (Madin-Darby Canine Kidney, Vero and PER.C6) are in clinical trials, and the first licenses for seasonal as well as pandemic H5N1 vaccines have been granted.
April 2009 – Suitability of PER.C6 cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics. Due to technical and regulatory requirements, the choice of cell lines for production of human influenza vaccines is limited. PER.C6 cells, among the most extensively characterized and documented cells, support growth of all influenza viruses tested to date, and can be grown to high densities in large bioreactors in the absence of serum or micro carriers.
March 2009 – A phase I clinical trial of a PER.C6 cell grown influenza H7 virus vaccine. Sixty healthy volunteers were intramuscularly vaccinated with two doses of split H7N1 virus vaccine containing 12 micrograms or 24 micrograms haemagglutinin alone or with aluminum hydroxide adjuvant (300 micrograms or 600 micrograms, respectively). The vaccine was well tolerated in all subjects and no serious adverse events occurred. The vaccine elicited low haemagglutination inhibition and microneutralization titers, although the addition of aluminum adjuvant augmented the antibody response.
May-August 2008 – Vaccines, biotechnology and their connection with induced abortion. “Diploid cells (WI-38, MRC-5) vaccines have their origin in induced abortions. Among these vaccines we fi nd the following: rubella, measles, mumps, rabies, polio, smallpox, hepatitis A, chickenpox, and herpes zoster. Nowadays, other abortion-tainted vaccines cultivated on transformed cells (293, PER.C6) are in the pipeline: flu, Respiratory Syncytial and parainfluenza viruses, HIV, West Nile virus, Ebola, Marburg and Lassa, hepatitis B and C, foot and mouth disease, Japanese encephalitis, dengue, tuberculosis, anthrax, plague, tetanus and malaria.”
November 2007 – Safety and efficacy in geese of a PER.C6-based inactivated West Nile virus vaccine. The mammalian cell line, PER.C6, was selected as the platform for West Nile Virus growth since both the neurovirulent strains NY99 and ISR98 that cause epidemics in humans and high mortality in geese, respectively. Initial studies on the correlates of protection induced by the vaccine indicate an important role for antibodies since geese were protected when injected intra-cranial with a mixture of serum from vaccinated, non-challenged geese and WNV. In all, these results provide a scientific basis for the development of an inactivated WNV vaccine based on NY99 produced on PER.C6 cells for human and equine use. Comment: Note that the safety for developing this vaccine was based on injecting West Nile Virus vaccine into the brains of geese.
April 2007 – Use of Cell Lines for the Production of Influenza Virus Vaccines: An Appraisal of Technical, Manufacturing, and Regulatory Considerations “PER.C6 cells were originally derived from embryonic human retinal cells that were immortalized by a known means of transformation, i.e., the E1 sequences from Adenovirus type 5.” Comment: immortalized cells, by definition, are cancer cells.
August 2006 – Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells(full text) “Mass vaccination for diseases such as AIDS, malaria and tuberculosis (TB) requires vaccine technology that can be produced on a large scale and that induces protective immunity. PER.C6 best candidate.
2006 – Approaches to the release of a master cell bank of PER.C6 cells; a novel cell substrate for the manufacture of human vaccines The PER.C6 cell line was developed at Crucell by the transfection of human primary embryonic retinoblasts with a transgene of E1 constructed with a minimum of E1 coding sequences to preclude homologous recombination generating replication-competent adenovirus, between E1 sequences in PER.C6 and adenovirus vectors with E1 deletions of the same molecular coordinates. We have developed a Master Cell Bank (MCB) of PER.C6 cells under serum-free conditions of suspension culture from a vial of PER.C6 cells obtained from Crucell.
March 2001 – The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines. Influenza viruses for vaccine production are currently grown on embryonated eggs. This manufacturing system conveys many major drawbacks such as inflexibility, cumbersome down stream processing, inability of some strains to replicate on eggs to high enough yields, and selection of receptor-binding variants with reduced antigenicity. These limitations emphasize the need for a cell line-based production system that could replace eggs in the production of influenza virus vaccines in a pandemic proof fashion. Here we present the efficient propagation of influenza A and B viruses on the fully characterized and standardized human cell line PER.C6.