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 vaccinesare 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.

Overlapping CD8 + and CD4 + T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach

“…Epitopes are mostly recognized as the antigenic determinants that represent the immunogenic portion of the protein antigen and provoke precise immune responses (Shi et al, 2015;Vivona et al, 2008). Several research findings revealed that epitope-based peptide vaccine could efficiently elicit defensive immune responses against miscellaneous pathogens, such as malaria (Oyarzún and Kobe, 2016), influenza virus (Staneková and Varečková, 2010), hepatitis B virus, hepatitis C virus (Firbas et al, 2006;He et al, 2015;Sominskaya et al, 2010), and HIV (human immunodeficiency virus) (Jin et al, 2009). However, In spite of the availability of the genome sequence in the GenBank database for emerging infectious pathogen, like RVFV, the immunity accompanying with protection is now largely unknown to the researchers.…”

DNA vaccine with discontinuous T‐cell epitope insertions into HSP65 scaffold as a potential means to improve immunogenicity of multi‐epitope Mycobacterium tuberculosis vaccine

“…Epitope-focused vaccine design is an appealing method, by which minimized antigen epitopes are designated to develop into a TB vaccine resulting in retaining one or more key epitopes while eliminating other potentially distracting or unnecessary features (20,34,35). Until now, much evidence has proved that epitope-focused vaccine could effectively protect against cancer and infectious diseases (36)(37)(38)(39)(40).…”

Computational vaccinology approach: Designing an efficient multi-epitope peptide vaccine againstCryptococcus neoformans var. grubii’sheat shock 70KDa protein

“…Multi-epitope peptide vaccines are immune-proteome derived-pathogen, compose of several peptide fragments of T-cell and B-cell epitopes that able to evoke highly targeted lymphocytes response and immunological memory (90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100). On one hand, peptide-based vaccines potentially have several benefits include they are cost-effective and easy in manufacturing process, highly stable, and diminished toxicity are generally confirmed in clinical studies.…”