Abstract
Vaccination is one of the most efficient tools for disease prevention, and a continuously growing field of research. However, despite progress, we still need more efficient and cost-effective vaccines that would improve access to those in need. In this review, we will describe the status of virus-vectored vaccine technology with a focus on adenoviral-based vaccines. Adenovirus (Ad) vaccines have proven to be efficient in military vaccinations against Ad4 and Ad7 and as highly efficient vectored vaccines against rabies. The question of how other adenovirus-based vaccines can become as efficient as the rabies vaccine is the underlying theme in this review. Here, we will first give an overview of the basic properties of vectored vaccines, followed by an introduction to the characteristics of adenoviral vectors and previously tested modifications of the vector backbone and expression cassettes, with a focus on how they can contribute to increased vaccine cost-effectiveness. Finally, we will highlight a few successful examples of research that have attempted to improve the use of adenoviral-based vaccines by improving the transgene immunogenicity.
Highlights
Vaccination has greatly reduced the burden of infectious diseases over the last 200 years, and clean water is the only health intervention proven to perform better than vaccination to overcome sickness and death [1]
As the vaccinia vector presents some safety issues due to the incapacity to be sufficiently attenuated for general use in humans, and is relatively poor at inducing T cells, adenoviruses seem to offer some of the best prospects for a generally applicable vaccine platform
For safety reasons and convenience, most adenovirus vaccine candidates are E1 deleted, as E1 controls the other early genes, disabling the expression of early genes. This deletion prevents the virus from spreading in the host and allows selection for recombinant viruses based on replicative capacity in E1-expressing cell lines [26]. ∆E1 adenoviruses have been used for vaccines in differIennt. tJ
Summary
Vaccination has greatly reduced the burden of infectious diseases over the last 200 years, and clean water is the only health intervention proven to perform better than vaccination to overcome sickness and death [1]. Further attenuation can come from the use of subunit vaccines which contain only a small fraction of the pathogen In this case, immunity is based on the antigens requirement for inducing disease or infection (e.g., diphtheria toxin or hepatitis B virus capsular antigen). The military-specific vaccine showed efficiency as well as long-lasting immunity, and was extremely safe with only 2/200,000 developing vaccine-related symptoms [6] Such a vaccine uses a safely replicating microorganism, delivered in the gut while avoiding the lungs, where it would have caused pathology. It allows in situ dose amplification (lowering production cost), offers easy administration, and leads to the induction of mucosal immunity While both replicating poxviruses and adenoviruses have been produced and encompass all the required qualities for an efficient and affordable vaccine, the experience from these vaccines has not been generalized for use against other pathogens. We will present some examples where replication-competent adenoviruses have been modified in ways that may render them more alike the rabies virus vaccine gold-standard
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