Vaccine technologies: From whole organisms to rationally designed protein assemblies

Abstract

Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines. While more tolerable, subunit vaccines tend to be less immunogenic. Attempts have been made to increase immunogenicity with the addition of adjuvants, either immunostimulatory molecules or an antigen delivery system that increases immune responses to vaccines. An area of extreme interest has been the application of nanotechnology to vaccine development, which allows for antigens to be expressed on a particulate delivery system. One of the most exciting examples of nanovaccines are rationally designed protein nanoparticles. These nanoparticles use some of the basic tenants of structural biology, biophysical chemistry, and vaccinology to develop protective, safe, and easily manufactured vaccines. Rationally developed nanoparticle vaccines are one of the most promising candidates for the future of vaccine development.

Keywords: Adjuvant; Nanoparticles; Rationally designed; SAPN; Vaccine.

Graphical abstract

Fig. 1

A timeline showing when different classes of vaccines became clinically available and the overlap of availability. Some vaccines like Hepatitis B technically fall into multiple classes such as subunit as well as nanovaccines. Lighter/dashed colors indicate that these classes will most likely remain important for the foreseeable future. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Types of protein assemblies that are used as vaccines carriers. (A) Vaults: The example shows the rat liver vault comprising 78 identical major vault protein chains (PDB-RCSB code 4V60). The view is perpendicular to the 39-fold symmetry axis. (B) VLPs: The example shows the RNA bacteriophage Q beta forming a T = 3 icosahedral particle (PDB-RCSB code 1QBE). The view is down the twofold axis of the icosahedron. (C) Ferritin: Shown is the octahedral structure of ferritin from the marine pennate diatom Pseudo-nitzschia multiseries (PmFTN) (PDB-RCSB code 4ZKW). The view is down the fourfold axis of the octahedron. (D) SAPNs: The example shows a SAPN composed of a pentameric (blue) and trimeric (cyan) coiled-coil domain displaying the trimeric coiled-coil epitope HRC (red) from the SARS coronavirus. The view is down the threefold axis of the icosahedron. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)