Immunogenicity of Biologies

Shankar, G., Shores, E., Wagner, C., and Mire-Sluis, A. 2006. Scientific and regulatory considerations on the immunogenicity of biologies. Trends in Biotechnology 24, 274-280. 

Rosenberg AS. Immunogenicity of biological therapeutics a hierarchy of concerns. Dev Biol 2003 112 15-21. 

Chamberlain P, Mire-Sluis AR. An overview of scientific and regulatory issues for the immunogenicity of biological products. In Immunogenicity of Therapeutic Biological Products, edited by Brown F, Mire-Sluis, pp. 3-11. Basil, Switzerland Karger AG, 2003. 

Traditionally, the duration of a toxicity study depends on the intended clinical use and disease duration. The potential immunogenicity of the human protein is a significant issue since antibody binding can partially or completely inhibit the biological activity of that protein, affect its catabolism or alter its distribution and clearance. Any multiple-dose study therefore should include evaluation of the impact of antibody formation, including their neutralizing capacity. However, antibody formation in itself should not be a reason for termination of a toxicity study, particularly if the antibodies are not neutralizing or do not alter the pharmacodynamics of the protein. 

Patten PA, Schellekens H. The immunogenicity of biopharmaceuticals lessons learned and consequences for protein drug development. In Brown F, Mire-Sluis AR, eds. Immunogenicity of Therapeutic Biological Products. Basel, Switzerland S. Karger, 2003. 

Levery, S.B., Weiss, J.B., Salyan, M.E.K., Roberts, C.E., Hakomori, S., Magnani, J.L. and Strand, M. (1992) Characterization of a series of novel fucose-containing glycosphingolipid immunogens from eggs of Schistosoma mansoni. journal of Biological Chemistry 267, 5542-5551. 

There are many techniques that can be employed to assess the immuno-genicity of a vaccine candidate, and laboratories interested in pursuing this objective should also explore other assays suited to their purposes. In this model, vaccine immunogenicity is measured by determining levels of anti-LHRH antibodies induced in mice immunized with lipopeptide or a nonlipi-dated peptide control. It is important to correlate vaccine immunogenicity with biological function, and we measure the reproductively capability of vaccinated female mice as an indication of vaccine efficacy. Techniques that determine testosterone and oestrogen levels are also useful. 

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