Emerging Concepts and Technologies in Vaccine Development

Abstract

Despite the success of vaccination to greatly mitigate or eliminate threat of diseases caused by pathogens, there are still known diseases and emerging pathogens for which the development of successful vaccines against them is inherently difficult. In addition, vaccine development for people with compromised immunity and other pre-existing medical conditions has remained a major challenge. Besides the traditional inactivated or live attenuated, virus-vectored and subunit vaccines, emerging non-viral vaccine technologies, such as viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer innovative approaches to address existing challenges of vaccine development. They have also significantly advanced our understanding of vaccine immunology and can guide future vaccine development for many diseases, including rapidly emerging infectious diseases, such as COVID-19, and diseases that have not traditionally been addressed by vaccination, such as cancers and substance abuse. This review provides an integrative discussion of new non-viral vaccine development technologies and their use to address the most fundamental and ongoing challenges of vaccine development.

Keywords: COVID19; cancer vaccines; infectious disease; nanoparticle vaccines; non-viral DNA-RNA vaccines; noncommunicable disease; substance abuse; virus-like particle vaccines.

Figure 1

Schematic of VLP vaccine production. The methodology to produce VLP vaccines is summarized in this cartoon. In brief, VLP vaccines are produced by transfecting eukaryotic cells or transforming bacterial cells with a DNA plasmid encoding an antigenic peptide attached to a viral capsid and/or other protein that is sufficient to form VLPs. The antigenic peptide is present on the outside of the VLP which becomes available for interaction with the immune system. Antigens conjugated with a chemical crosslinker can also be attached to VLPs containing external proteins conjugated to a complementary chemical crosslinker, which will result in antigens being linked to the VLP and being presented on the outside edges. Figure created using BioRender software.

Figure 2

Schematic of NP vaccine production. The methodology to produce NP vaccines is summarized in this cartoon. In brief, NP vaccines are produced by assembling a complex of antigens, a linker molecule, and a carrier molecule by chemical conjugation. Figure created using BioRender software.

Figure 3

Methods of improving DNA vaccines. The various methods that have been developed to improve the stability and immunogenicity of DNA vaccines are summarized in this chart. A number of design and delivery mechanisms have contributed to improving the performance of nucleic acid vaccines, such as methods of clinical delivery, genetic engineering, and linking nucleic acid vaccines to cells or biomolecules. Figure created using BioRender software.

Figure 4

Methods of improving RNA vaccines. The various methods that have been developed to improve the stability and immunogenicity of RNA vaccines are summarized in this chart. A number of design and delivery mechanisms have contributed to improving the performance of nucleic acid vaccines, such as methods of clinical delivery, genetic engineering, and linking nucleic acid vaccines to cells or biomolecules. Figure created using BioRender software.

Figure 5

Methods of improving DNA and RNA vaccines. The various methods that have been developed to improve the stability and immunogenicity of both DNA and RNA vaccines are summarized in this chart. A number of design and delivery mechanisms have contributed to improving the performance of nucleic acid vaccines, such as methods of clinical delivery, genetic engineering, and linking nucleic acid vaccines to cells or biomolecules. Figure created using BioRender software.