title: Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.
abstract: Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.
authors.affiliation: a Biotechnology Center, Facultad de Ingeniería y Tecnología, Universidad San Sebastián , Concepción , Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Oyarzún
authors.affiliation: b School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Center, University of Queensland , Brisbane , Australia.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
mesh_terms: D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D014614:Vaccines, Synthetic
keywords: CD4+ T-cell epitopes; epitope-based vaccines; immunoinformatics; in-silico vaccine design; recombinant protein vaccines