Vector-based genetically modified vaccines: Exploiting Jenner’s legacy

Abstract

The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner's vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors that may help us control other major scourges of mankind.

ΦX174 Attenuation by Whole Genome Codon Deoptimization

“…Empirically developed (e.g. serial passage viral adaptation) vaccines have saved millions of lives over the last century, yet methodological improvements make rationally designed, recombinant vaccines attractive because they can be rapidly produced and specifically engineered for safety and effectiveness (46)(47)(48)(49)(50) . One proposed method of generating recombinant vaccines involves making many synonymous, attenuating changes to viral genomes, i.e.…”

Newcastle disease virus co‐expressing interleukin 7 and interleukin 15 modified tumor cells as a vaccine for cancer immunotherapy

“…NDV can selectively replicate in tumor cells, as most of these cells are defective in interfering pathways . Therefore, NDV has been used clinically as an oncolytic agent against many types of cancer …”

Protein and modified vaccinia virus Ankara-based influenza virus nucleoprotein vaccines are differentially immunogenic in BALB/c mice

“…These cells are induced by natural infection but are induced V C 2017 British Society for Immunology, Clinical and Experimental Immunology, 190: [19][20][21][22][23][24][25][26][27][28] inefficiently by inactivated influenza vaccines (reviewed in [11]) [12][13][14]. These cells are induced by natural infection but are induced V C 2017 British Society for Immunology, Clinical and Experimental Immunology, 190: [19][20][21][22][23][24][25][26][27][28] inefficiently by inactivated influenza vaccines (reviewed in [11]) [12][13][14].…”

“…Virus-specific CD8 1 cytotoxic T cells predominantly recognize internal viral antigens, such as matrix (M1) and nucleoprotein (NP), that are relatively conserved and contain epitopes shared by various subtypes of influenza virus. These cells are induced by natural infection but are induced V C 2017 British Society for Immunology, Clinical and Experimental Immunology, 190: [19][20][21][22][23][24][25][26][27][28] inefficiently by inactivated influenza vaccines (reviewed in [11]) [12][13][14]. It has been shown that cross-reactive virusspecific CD8 1 cytotoxic T cells contribute to reduction of disease duration and severity after infection with a heterologous influenza virus [12,15].…”

“…Viral vaccine vectors, such as modified vaccinia virus Ankara (MVA), have been shown to efficiently induce antigen-specific humoral and cellular responses (reviewed in [24,25]). Recombinant (r)MVA vaccines have been tested extensively in various animal models and multiple clinical trials against different pathogens, including influenza virus, and has proved that the use of rMVA-based vaccines is safe [25][26][27][28]. As it is relatively easy to insert genes encoding antigens of interest into the genome of MVA, recombinant (r)MVA-based vaccines can be rapidly produced [24,25].…”