Foot and mouth disease (FMD) virus: Quantification of whole virus particles during the vaccine manufacturing process by size exclusion chromatography

• Published in: Vaccine 2011-09, Vol.29 (41), p.7182-7187
• Main Authors: Spitteler, Marcelo A, Fernández, Ignacio, Schabes, Erika, Krimer, Alejandro, Régulier, Emmanuel G, Guinzburg, Mariela, Smitsaart, Eliana, Levy, M. Susana
• Format: Article
• Language: English
• Subjects: 140S (146S); absorption; Accuracy; active ingredients; Allergy and Immunology; Applied microbiology; Atoms & subatomic particles; automation; Biological and medical sciences; Biosynthesis; cattle; Chromatography; Chromatography, Gel - methods; FMDV; Foot and mouth disease (FMD) vaccine; foot-and-mouth disease; Foot-and-mouth disease virus; Foot-and-Mouth Disease Virus - isolation & purification; Fundamental and applied biological sciences. Psychology; goats; inactivated vaccines; Manufacturers; Manufacturing; Manufacturing industry; Methods; Microbiology; Miscellaneous; Molecular weight; Mortality; sheep; size exclusion chromatography; Size exclusion chromatography (SEC); Sucrose; swine; Technology, Pharmaceutical - methods; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Inactivated; Viral diseases; Viral infections; Viral Load; Viral Vaccines; Virology; Virology - methods; viruses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.05.078

Foot and mouth disease (FMD) is a highly infectious viral disease that affects cattle, sheep, goats and swine causing severe economic losses worldwide. The efficacy of inactivated vaccines is critically dependent on the integrity of foot and mouth disease virus (FMDV) particles. The recommended method to quantify the active ingredient of vaccines is the 140S quantitative sucrose density gradient analysis. This method has been an immensely valuable tool over the past three decades but it is highly operator dependent and difficult to automate. We developed a method to quantify FMDV particles during the vaccine manufacturing process that is based on separation of components by size-exclusion chromatography and measurement of virus by absorption at 254nm. The method is linear in the 5–70μg/mL range, it is applicable to different FMDV strains, and has a good correlation with the 140S test. The proposed method uses standard chromatographic media and it is amenable to automation. The method has potential as a process analytical technology and for control of final product by manufacturers, international vaccine banks and regulatory agencies.