Effect of thiomersal on dissociation of intact (146S) foot-and-mouth disease virions into 12S particles as assessed by novel ELISAs specific for either 146S or 12S particles

• Published in: Vaccine Vol. 29; no. 15; pp. 2682 - 2690
• Main Authors: Harmsen, M.M, Fijten, H.P.D, Westra, D.F, Coco-Martin, J.M
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 24-03-2011; Elsevier; Elsevier Limited
• Subjects: Acidification; Allergy and Immunology; Animal diseases; Animals; antigens; Applied microbiology; Asia; Atoms & subatomic particles; Biological and medical sciences; capsid; Chromatography; Degradation products; dissociation; domain antibody fragments; enzyme-linked immunosorbent assay; Enzyme-Linked Immunosorbent Assay - methods; field strains; Foot & mouth disease; foot-and-mouth disease; Foot-and-mouth disease virus; Foot-and-Mouth Disease Virus - chemistry; Foot-and-Mouth Disease Virus - drug effects; Fundamental and applied biological sciences. Psychology; Heat; Heat treatment; immune response; Immunogenicity; international bank; manufacturing; Merthiolate; Microbiology; monoclonal-antibodies; passive-immunization; Preservatives; protein subunit; Proteins; sandwich elisa; serotypes; shelf life; storage time; Studies; Sucrose; thermal-stability; Thimerosal; Thimerosal - metabolism; United States; vaccine; Vaccine stability; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral integrity; Viral Vaccines - chemistry; virion; Virion - chemistry; Virion - drug effects; Virology - methods; whole virus-particles; Asia; United States; Viral integrity; Thimerosal; Merthiolate; Vaccine stability; Foot and mouth disease; Thiomersal; Vaccine; Infection; Viral disease; Antiseptic; Mercury Organic compounds; Veterinary; ELISA assay
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.01.069

Abstract Intact (146S) foot-and-mouth disease virions (FMDVs) can dissociate into specific (12S) viral capsid degradation products. Using two single-domain antibody fragments that bind specifically to either 146S or 12S particles we developed two ELISAs for the quantification of these particles in FMDV antigen preparations used for vaccine manufacturing. Only O serotype strains are detected in the 146S specific ELISA whereas strains of most serotypes are detected in the 12S specific ELISA. However, the 146S concentration of A and Asia 1 serotype strains could be measured indirectly using the 12S specific ELISA by prior conversion of 146S into 12S particles by heat treatment. This allowed us to demonstrate that addition of the preservative thiomersal to FMDV antigens stimulates the dissociation into 12S particles of O, A and Asia 1 serotype strains upon prolonged storage at 4 °C. FMDV dissociation is known to result in a strongly reduced immunogenicity, which was experimentally confirmed here. Therefore, we recommend to omit thiomersal from FMD vaccines to increase its shelf life.