MDCK Cells (Canine)

From Tenpenny Research Library
Jump to navigation Jump to search

MDCK cells are a line of canine (dog) epithelial cells that grow readily in culture and form confluent monolayers with relatively low permeability (varies between clones). Often used as a general model for epithelial cells. (Author: John Lackie for Dictionary of Cell and Molecular Biology – Online.)

Madin-Darby canine kidney (MDCK) cells

Use of MDCK Cells for manufacture of inactivated Influenza Vaccines: Introduction Philip R. Krause, M.D. (ppt) or Use of Madin-Darby Canine Kidney (MDCK) Cells

July 24, 2017 – Safety and immunogenicity of an inactivated cell culture-derived H7N9 influenza vaccine in healthy adults: A phase I/II, prospective, randomized, open-label trial “We conducted a phase I/II clinical trial to evaluate the safety and immunogenicity of a Madin-Darby canine kidney (MDCK) cell-grown inactivated H7N9 influenza vaccine for pandemic preparedness purposes. … Our study demonstrated that the H7N9 influenza vaccine containing 30 µg HA with aluminum hydroxide adjuvant was immunogenic and safe in adults aged 20–60 years.”

October 26, 2016 – Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories (full text) “To make the delivery user-friendly, the quadrivalent vaccine has been developed as a ready-to-use liquid vaccine and the nasal delivery devices have been upgraded. Considering the unpredictable demand for influenza vaccines in India, and worldwide in general, pre-ordering for large quantity of eggs is a major challenge. An obvious solution to this problem is the development of a 'tissue culture-based LAIV. A well-characterized Madin-Darby 'canine' kidney' (MDCK) cell bank has been prepared by SIIPL and experimental batches have been prepared. Further work to develop GMP LAIV lots is underway. The SIIPL is aiming towards a MDCK-based quadrivalent liquid LAIV that will have an ideal influenza vaccine profile including safety, efficacy, stability and ease of administration, as well as high capacity to rapidly increase the production.”

June 24, 2014 – Performance characteristics of qualified cell lines for isolation and propagation of influenza viruses for vaccine manufacturing “MDCK cell lines proved to be highly sensitive for virus isolation. Compared to the virus sequenced from the original specimen, viruses passaged three times in the MDCK lines showed up to 2 amino acid changes in the hemagglutinin. Antigenic stability was also established by hemagglutination inhibition titers comparable to those of the corresponding reference virus. Viruses isolated in any of the three MDCK lines grew reasonably well but variably in three MDCK cells and in VERO cells at pilot-scale. These results indicate that influenza viruses isolated in vaccine certified cell lines may well qualify for use in vaccine production.” Comment: (MDCKis a canine cell line established in 1958 from a healthy Cocker Spaniel. Some MDCK derivatives have been found to be highly tumorigenic. Highly tumorigenic cell Substrates have never been used to manufacture viral vaccines.

April 11, 2014 – Matrix and Backstage: Cellular Substrates for Viral Vaccines (full text) “To provide more robust vaccine research options, and because of some disadvantages associated with manufacture in primary cells, other cell substrates have been developed. Today, the spectrum of substrates used for production of licensed and investigational vaccines ranges from primary cells (sometimes still within the animal) to designed continuous cell lines. Properties of these substrates with focus on historical aspects pertaining to human vaccines will be summarized in this review.”

August 16, 2013 – Clinical Trial to Evaluate the Safety and Immunogenicity of a Trivalent Surface Antigen Seasonal Influenza Vaccine Produced in Mammalian Cell Culture and Administered to Young and Elderly Adults with and without A(H1N1) Pre-Vaccination (full text)

  • “Competing interests: This study was funded by Novartis Vaccines, the employer of SM and DB.”
  • “In contrast to other influenza vaccines, this trivalent vaccine was produced in a mammalian cell line (Madin-Darby canine kidney (MDCK) cells)
  • “Solicited local (ecchymosis, erythema, induration, swelling, pain) and systemic (chills/shivering, malaise, myalgia, arthralgia, headache, sweating, fatigue, fever) reactions that occurred within 3 days of the day of vaccination were used as indicators of reactogenicity. As such, they were judged to be at least possibly related to the administration of the study vaccine. If a local or systemic reaction continued beyond day 4, it was additionally recorded as an AE.”

July 2013 – An MDCK Cell Culture-Derived Formalin-Inactivated Influenza Virus Whole-Virion Vaccine from an Influenza Virus Library Confers Cross-Protective Immunity by Intranasal Administration in Mice “We then produced a formalin-inactivated whole-virion vaccine from the MDCK cell-cultured A/duck/Hokkaido/Vac-3/2007 (H5N1) P22 virus. Intranasal immunization of mice with this vaccine protected them against challenges with lethal influenza viruses of homologous and heterologous subtypes. We further demonstrated that intranasal immunization with the vaccine induced cross-reactive neutralizing antibody responses against the homotypic H5N1 influenza virus and its antigenic variants and cross-reactive cell-mediated immune responses to the homologous virus, its variants within a subtype, and even an influenza virus of a different subtype. These results indicate that a rapid model for emergency vaccine production may be effective for producing the next generation of pandemic influenza virus vaccines.

May 1, 2013 – MDCK cell culture-derived formalin-inactivated influenza whole virion vaccine from an influenza virus library conferred cross-protective immunity by intranasal administration in mice “We then produced a formalin-inactivated whole virion vaccine from the MDCK-cell cultured A/duck/Hokkaido/Vac-3/2007 (H5N1) P22.The intranasal immunization of mice with this vaccine protected them against the challenge with lethal influenza viruses of homologous and heterologous subtypes. ” Comment: See MDCK Cells (dog) and Formalin

October 2, 2012 – Title: Methods and compositions for expressing negative-sense viral RNA in canine cells (patent)”Thus, the system and methods described herein are useful for the rapid production in canine cell culture of recombinant and reassortant influenza A and B viruses, including viruses suitable for use as vaccines, including live attenuated vaccines. Vaccines prepared according to methods of the invention may be delivered intranasally or intramuscularly.”

February 2011 – Safety of MDCK cell culture-based influenza vaccines (pfd)

January 2011 – Production of Inactivated Influenza H5N1 Vaccines from MDCK Cells in Serum-Free Medium (full text)

June 2011 – Heterogeneity of the tumorigenic phenotype expressed by madin-darby canine kidney cells. “The results revealed lot-to-lot variations in the tumorigenicity of MDCK cells, which were reflected by their tumor-inducing efficiency (threshold cell dose represented by mean tumor-producing dose; log10 50% endpoints of 5.2 for vial 1 and 4.4 for vial 2, and a tumor-producing dose of 5.8 for vial 3) and mean tumor latency (vial 1, 6.6 wk; vial 2, 2.9 wk; and vial 3, 3.8 wk). These studies provide a reference for further characterization of the MDCK cell neoplastic phenotype and may be useful in delineating aspects of neoplastic development in vitro that determine tumor-forming capacity. Such data also are useful when considering MDCK cells as a reagent for vaccine manufacture.”

October 18, 2010 – Production and antigenic properties of influenza virus from suspension MDCK-siat7e cells in a bench-scale bioreactor

October 15, 2010 – Rapidly produced flu vaccine may be safe, effective

September 2010 – MDCK and Vero cells for influenza virus vaccine production: a one-to-one comparison up to lab-scale bioreactor cultivation.

August 2010 – Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process.

August 2010 – A new MDCK suspension line cultivated in a fully defined medium in stirred-tank and wave bioreactor

May 2010 – Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: In vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells

April 2010 – Human RNA Polymerase I-Driven Reverse Genetics for Influenza A Virus in Canine Cells (full text)

February 2010 – Cloning and assessment of tumorigenicity and oncogenicity of a Madin-Darby canine kidney (MDCK) cell line for influenza vaccine production.

December 2009 – Continuous cell lines as a production system for influenza vaccines.

October 2009 – Use of MDCK cells for production of live attenuated influenza vaccine

September 2009 – Safety and immunogenicity of a novel influenza subunit vaccine produced in mammalian cell culture.(full text)

June 2009 – Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines).

February 2009 – HPLC-based quantification of haemagglutinin in the production of egg- and MDCK cell-derived influenza virus seasonal and pandemic vaccines. Here, we present data demonstrating that this RP-HPLC method is also highly suitable for HA quantification of active and BPL- or formaldehyde-inactivated egg-based and MDCK cell-based whole virus samples, including egg allantoic harvest, and in final (monovalent) subunit vaccines, including those for pandemic H5N1 strains and for virosomal vaccines. Because of its high sensitivity, the RP-HPLC assay has shown its enormous value in supporting small scale MDCK-based (H5N1) influenza virus production models.

January 2009 – Safety, tolerability and immunogenicity of a mammalian cell-culture-derived influenza vaccine: a sequential Phase I and Phase II clinical trial.

December 9, 2008 – Timely production of A/Fujian-like influenza vaccine matching the 2003-2004 epidemic strain may have been possible using Madin-Darby canine kidney cells.

October 2008 – Microcarrier-based MDCK cell culture system for the production of influenza H5N1 vaccines.

September 2008 – Growth Determinants for H5N1 Influenza Vaccine Seed Viruses in MDCK Cells (full text)

June 2008 – A quantitative risk assessment of exposure to adventitious agents in a cell culture-derived subunit influenza vaccine. “As only a limited range of mammalian viruses can grow in MDCK cells, similar to embryonated eggs, MDCK cells can act as an effective filter for a wide range of adventitious agents that might be introduced during vaccine production. However, the introduction of an alternative cell substrate (for example, MDCK cells) into a vaccine manufacturing process requires thorough investigations to assess the potential for adventitious agent risk in the final product, in the unlikely event that contamination should occur.”

2008 – Cell-based influenza vaccines: progress to date.

April 10, 2007 – Use of Cell Lines for the Production of Influenza Virus Vaccines: An Appraisal of Technical, Manufacturing, and Regulatory Considerations (pdf) “Of the various continuous mammalian cell lines that have been adequately tested – including diploid cell lines (MRC-5, WI-38, and FRhl-2) and continuous cell lines (PER.C6, NIH-3T3, BHK, CHO, Vero and MDCK) – only Vero, PER.C6 and MDCK have consistently yielded influenza viruses titers that are sufficiently high enough to be considered commercially viable.

August 1997 – Immunogenicity and Reactogenicity of Influenza Subunit Vaccines Produced in MDCK Cells or Fertilized Chicken Eggs (pdf)

May 1, 1982 – The MDCK epithelial cell line expresses a cell surface antigen of the kidney distal tubule.