Self-assembling protein nanoparticles in the design of vaccines

Jacinto López-Sagaseta,Enrico Malito,Rino Rappuoli,Matthew J Bottomley

doi:10.1016/j.csbj.2015.11.001

Jacinto López-Sagaseta, Enrico Malito + Show 2 more

Open Access

https://doi.org/10.1016/j.csbj.2015.11.001

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Abstract

For over 100years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.

Highlights

Vaccines are among the most outstanding achievements in human medical history
A landmark study by Brown and coworkers showed that a chimeric recombinant form of hepatitis B core antigen (HBcAg) genetically fused to the foreign foot-and-mouth disease virus (FMDV) peptide epitope could be produced in a viral expression system and self-assembled into nanoparticles displaying the FMDV epitope
This recent example applied to HCV builds on the epitope-scaffold rational design strategy that emerged in previous attempts to graft human immunodeficiency virus (HIV) epitopes onto heterologous protein scaffolds [97], and effectively combines this approach with the multivalent nanoparticle format

Summary

Introduction

Vaccines are among the most outstanding achievements in human medical history. Through their power to prevent or reduce the burden of infectious diseases they make an enormous global impact by improving the life quality of both humans and animals. A variety of naturally occurring proteins can self-assemble into nanoparticles that are highly symmetric, stable, and structurally organized, with diameters of 10–150 nm [9,10], a highly suitable size range for optimal interactions with various cells of the immune system [8,11] These nanoparticles normally play diverse physiological roles, but are of particular interest in the context of vaccine design because they can be used as self-assembling platforms for the display of an arranged and well-ordered matrix of a particular immunogen, thereby mimicking the repetitive surface architecture of a natural microbe, e.g. a spherical virus capsid [12]. Synthetic nanoparticles made from non-polypeptide polymers, metals, or other solid supports, and the use of encapsulating particles as vaccine delivery systems are beyond the scope of the current review, and the reader is directed to alternative sources [31,32,33]

Biochemistry and applications of bionanoparticle antigens

Bacterial protein platforms

Micellar nanoparticles

New protein platforms

Findings

Conclusions