Abstract

To date, vaccination has become one of the most effective strategies to control and reduce infectious diseases, preventing millions of deaths worldwide. The earliest vaccines were developed as live-attenuated or inactivated pathogens, and, although they still represent the most extended human vaccine types, they also face some issues, such as the potential to revert to a pathogenic form of live-attenuated formulations or the weaker immune response associated with inactivated vaccines. Advances in genetic engineering have enabled improvements in vaccine design and strategies, such as recombinant subunit vaccines, have emerged, expanding the number of diseases that can be prevented. Moreover, antigen display systems such as VLPs or those designed by nanotechnology have improved the efficacy of subunit vaccines. Platforms for the production of recombinant vaccines have also evolved from the first hosts, Escherichia coli and Saccharomyces cerevisiae, to insect or mammalian cells. Traditional bacterial and yeast systems have been improved by engineering and new systems based on plants or insect larvae have emerged as alternative, low-cost platforms. Vaccine development is still time-consuming and costly, and alternative systems that can offer cost-effective and faster processes are demanding to address infectious diseases that still do not have a treatment and to face possible future pandemics.

Highlights

  • To date, vaccination has become one of the most effective strategies to control and reduce infectious diseases, preventing millions of deaths worldwide

  • Advances in genetic engineering have enabled the development of new platforms for protein expression, such as mammalian cells, plants or insect larvae, and the emergence of new technologies applied to vaccine development, such as nanotechnology

  • MRNA vaccines have emerged as a promising vaccination strategy to face pandemic infectious diseases such as the recent COVID-19 disease. This platform led to a rapid vaccine development, and two novel mRNA vaccines were approved: Comirnaty® (Pfizer, New York, USA and BioNTech, Mainz, Germany) and COVID-19 Vaccine Moderna (Moderna, Cambridge, MA, USA), both of them nucleosidemodified messenger RNA produced by using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2

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Summary

Historical Perspective of Vaccine Development

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The term vaccine was originated after the Latin word vacca, which means cow [3] This finding opened the era of vaccination and led to the discovery of further vaccines against other infectious diseases. Advances in culture techniques defined a landmark success in the second golden age of vaccinology (1940–1970), leading to the development of vaccines for viral infections such as poliomyelitis, measles, mumps and Biomolecules 2021, 11, 1072. In addition to traditional vaccines based on whole-pathogens and subunit vaccines, new vaccines technologies, such as live genetically modified pathogens, vectored vaccines (that use viruses as delivery systems for foreign antigens) and DNA vaccines, are already approved for their commercialization [12]. The One Health approach for Ebola aims for a shared benefit, i.e., the vaccination of wild apes in order to protect both apes and human [13]

The Immune System and the Rationale of Vaccination
Route of Administration
New Strategies for Vaccine Development
Pathogen-Based Vaccines
Viral-Vector-Based Vaccines
Nucleic Acid–Based Vaccines
Protein-Based Vaccines
Nanotechnology Applied to Subunit Vaccines
VLPs and Small Subviral Particles
Ferritin Cages
Vault Particles
Encapsulins
In Silico Designed Nanoparticles
Traditional Platforms for Protein Vaccine Manufacturing
Insect Cells
Mammalian Cells
Alternative Platforms for Protein Vaccine Manufacturing
New Approaches in Yeast Platform
Transgenic Animals
Insects
Plant-Based Systems
Microalgae
Findings
Conclusions
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