Advances in Predicting and Manipulating the Immunogenicity of Biotherapeutics and Vaccines

Abstract

Therapeutic proteins are vital to the future of human health provision and the survival and profitability of the global pharmaceutical industry. Returns from protein therapeutics are experiencing unprecedented growth: both their number and their economic dividend have increased by an order of magnitude in the last 10 years. The potential immunogenicity of protein therapeutics raises many clinical and safety concerns. Many poorly understood factors relating to both product and host affect immune responses. Available laboratory measurement of immunogenicity is of little utility for predicting the clinical properties of biotherapeutics. Coupled with assay variability and standardization issues, this precludes adequate prediction of the biological or clinical responses of therapeutic proteins, arguing for the utilization of informatic strategies in the analysis and prediction of protein immunogenicity. Currently, many unresolved issues must be addressed and thus circumvented before effective prediction can become routine.

Transferon™, a peptide mixture with immunomodulatory properties is not immunogenic when administered with various adjuvants

“…Today, the use of protein-derived drugs is becoming more significant, because they are effective and specific therapies for chronic degenerative diseases. Therapeutic proteins also have fewer adverse effects than drugs that are generated by chemical synthesis (Flower 2009). Further, proteins are the most immunogenic particles among all biomolecules, and can induce immunogenic responses when administered.…”

New developments and concepts related to biomarker application to vaccines

“…What also needs to be capitalized on is the wealth of information in other fields such as biotherapeutics (e.g. monoclonal antibody treatment for diseases) which may be of relevance to vaccines (Flower, 2009). Ironically for vaccines, biotherapeutics is a field where immunogenicity is highly undesirable as it can lead to reduced efficacy of the treatment, can manifest as allergic reactions (swelling, skin eruption, fever, anaphylaxis), or lead to potentially life‐threatening symptoms when antibody mediated neutralization of the therapeutic protein cross‐reacts with an endogenous protein of vital function.…”

Pharmacovigilance, Drug Repositioning, and Virtual Screening

“…In 2009, I wrote: "Much as the world finds itself in financial crisis, so does the pharmaceutical industry, albeit for different reasons, namely: regulatory changes; dwindling corporate drug pipelines; recurrent patent expiries as over 30 small-molecule drugs come offpatent by 2014; and the threat from generics and super-generics, for which revenues may exceed $US84 billion by the end of 2010; coupled with failure to exploit new technology and new targets emerging from post-genomic science. These have all conspired to stymie the global pharmaceutical endeavour and biologic therapies, such as vaccines and protein therapeutics, have grown in significance" [1]. While this may have been somewhat overtaken events, it nonetheless retains more than a remnant of truth.…”