Peptide-based synthetic vaccines.

Chemical Science View Article Online Open Access Article. Published on 17 December 2015. Downloaded on 26/07/2017 10:50:38. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. MINIREVIEW View Journal | View Issue Peptide-based synthetic vaccines Cite this: Chem. Sci., 2016, 7, 842 Mariusz Skwarczynski*a and Istvan Tothabc Classically all vaccines were produced using live or attenuated microorganisms or parts of them. However, the use of whole organisms, their components or the biological process for vaccine production has several weaknesses. The presence of immunologically redundant biological components or biological impurities in such vaccines might cause major problems. All the disadvantageous of traditional vaccines might be overcome via the development of fully synthetic peptide-based vaccines. However, once minimal antigenic epitopes only are applied for immunisation, the immune responses are poor. The use of an Received 14th October 2015 Accepted 14th December 2015 adjuvant can overcome this obstacle; however, it may raise new glitches. Here we briefly summarise the current stand on peptide-based vaccines, discuss epitope and adjuvant design, and multi-epitope and nanoparticle-based vaccine approaches. This mini review discusses also the disadvantages and benefits DOI: 10.1039/c5sc03892h associated with peptide-based vaccines. It proposes possible methods to overcome the weaknesses of www.rsc.org/chemicalscience the synthetic vaccine strategy and suggests future directions for its development. Introduction Vaccination is among the most successful medical treatments ever developed. This prophylaxis had a long journey through history to become one of humanity's key achievements; from early immunisation in China, centuries ago, through to Edward a The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia 4072, Australia. E-mail: b The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia c Jenner's works in the eighteenth century – when the word “vaccination” was introduced for the rst time – up to these modern times when recombinant protein-based vaccines are increasingly becoming popular. Despite the advances in the eld, classical vaccination using whole organisms is still common. Whole pathogen immunisations usually produce long lasting immunity; however, they are not without drawbacks. For example, the safety of this form of vaccination is one of the major concerns as it may cause autoimmune or strong allergic responses. Interestingly, allergic shock is oen related not to the presence of pathogen itself but rather, it is caused by The University of Queensland, School of Pharmacy, Brisbane, QLD 4072, Australia Mariusz Skwarczynski completed his PhD in Chemistry at Wroclaw University of Technology, Poland. His postdoctoral training began at Tokushima Bunri University and then he joined the laboratory of Professor Yoshiaki Kiso at Kyoto Pharmaceutical University, Japan. In 2004 he was awarded with Japan Society for the Promotion of Science fellowship to conduct research on paclitaxel prodrugs. In 2008 he joined Professor Istvan Toth group at University of Queensland (Australia) to work on drug, gene and vaccine delivery. He received Vice-Chancellor Fellowship at University of Queensland in 2010. Since then his research is mainly focused on nanotechnology-based vaccine delivery strategies. 842 | Chem. Sci., 2016, 7, 842–854 Professor Toth is a chemical engineer with a research focus on medicinal chemistry. He was awarded his PhD in 1972 and has since worked in Hungary, Canada and the United Kingdom before relocating to Australia in 1998. His major research interests are drug delivery, immunoadjuvants, synthetic vaccines and gene delivery. His research has attracted over $60 million in competitive grants, research contracts and investment funds in the past 10 years. He has over 300 peer-reviewed publications, 43 patents, and an excellent track record in research commercialization as a key founder of Alchemia (ASX listed), Implicit Bioscience Pty Ltd, Neurotide Pty Ltd and TetraQ (the commercial arm of Centre of Integrated Preclinical Drug Development). This journal is © The Royal Society of Chemistry 2016 View Article Online Open Access Article. Published on 17 December 2015. Downloaded on 26/07/2017 10:50:38. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Minireview contamination from the medium on which microorganism was grown (e.g. eggs, antibiotics). Attenuation or inactivation of such vaccines might not be perfect and the pathogen may return to its virulent state. One of the most prominent examples of such vaccine defectiveness was the “Lübeck disaster”, when, in 1930, 67 babies among the 249 vaccinated with tuberculosis vaccine (BCG) died.1 Shedding of the pathogen to the environment, during vaccine manufacture, is the other problem and infections of staff during the production process have been also reported.2 Manufacturing difficulties of some pathogen (e.g. malaria sporozoites), poor vaccine stability and the need for a “cold chain” are other signicant disadvantages of classical vaccines. Some of the vaccines cannot even use the whole cell approach (e.g. cancer vaccines, due to tumour similarity to healthy human cells). Subunit vaccines utilising only part of the whole pathogen are more controllable and can be produced without the use of the pathogen itself (e.g. recombinant proteins). They are a very attractive alternative to the whole pathogen approach and have become extensively popular in the modern era. However, they are still not perfectly safe, and cause side effects and production difficulties similar to whole pathogen strategies. For example whole protein-based approach was largely abandoned in the case of the vaccine against Group A Streptococcus which was targeting surface protein (M-protein) of the bacteria due to potential protein-triggered autoimmunity.3 In addition to problems associated with protein purities (these are normally produced using microorganisms), there are common stability issues, large scale protein expression difficulties, difficulties with the introduction of desired post-translational modication (e.g. glycosylation) into recombinant proteins and poor or undesired immune responses (inammation, autoimmunity, etc.). Therefore, the use of only minimal antigenic epitopes which can trigger the desired immune responses appears to be the smart approach to develop safe vaccines. The synthetic peptide-based vaccines may have such a capacity. They may become the unique medication of the future capable of delivering not only protection against diseases but may turn into the therapeutic tool to treat them. Vaccination and immunity A vaccine, similar to a natural pathogen, at rst, needs to be recognised by an animal/human defence system as an “enemy” to trigger a cascade of immune resp (...truncated)