Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

Abstract

Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases.

Keywords: Nanoparticle vaccine; anticancer vaccine.; cellular immunity; lymphatic delivery; repetitive antigen display; vaccine nanotechnology.

Figure 1

Schematics of a viral vaccine, a subunit vaccine, and a representative nanoparticle vaccine highlighting the strengths and shortcomings of each platform. Nanoparticle vaccines can be engineered to mimic viruses in terms of morphology, antigen display, and adjuvanticity.

Figure 2

Synthetic nanoparticles for vaccine delivery.

Figure 3

(A) Schematics illustrating the mechanisms behind and advantages of lymph node delivery by nanoparticle vaccines. Nanoparticles can exploit both cell-mediated and convective transport for lymph node localization. Particles that enter lymph nodes via interstitial-lymphatic drainage are captured by lymph node-resident macrophages. Enhanced antigen delivery by nanoparticles facilitates antigen presentation and T cell activation. (B) Fluorescence microlymphangiography imaging of 100 nm and 25 nm nanoparticles following tail based injection. 25 nm particles more effectively traverse through the lymphatic network. (C) 25 nm nanoparticles can more efficiently accumulate in lymph nodes as compared to 100 nm nanoparticles as evidenced by fluorescence microscopy. Images in (B)(C) are reproduced with permission from ref. 14, 2007 NPG.

Figure 4

(A) Schematics showing multivalent interactions by nanoparticle vaccines promote B cell receptor clustering and facilitate receptor-mediated internalization. (B) Schematics illustrating enhanced binding of multimeric immune factors, such as IgM and complement factors, to nanoparticle vaccines.