Nano toolbox in immune modulation and nanovaccines

Abstract

Despite the great success of vaccines over two centuries, the conventional strategy is based on attenuated/altered microorganisms. However, this is not effective for all microbes and often fails to elicit a protective immune response, and sometimes poses unexpected safety risks. The expanding nano toolbox may overcome some of the roadblocks in vaccine development given the plethora of unique nanoparticle (NP)-based platforms that can successfully induce specific immune responses leading to exciting and novel solutions. Nanovaccines necessitate a thorough understanding of the immunostimulatory effect of these nanotools. We present a comprehensive description of strategies in which nanotools have been used to elicit an immune response and provide a perspective on how nanotechnology can lead to future personalized nanovaccines.

Keywords: immune modulation; immune response; nano toolbox; nanovaccine; vaccine.

Figure 1

The basics of nanovaccines and their significance. (A) Nanovaccines comprise a selected antigen conjugated to a nanomaterial and an adjuvant to elicit immunogenic response. Multiple antigen epitopes (denoted by red and blue antigens) can be loaded onto the surface of the NPs. Nanomaterial and adjuvant types vary depending on the infection, tissue type, and the immune response required. (B) NPs aid efficient vaccine targeting to the desired cell and its receptors, thereby minimizing side effects. They increase the duration of antigen-receptor engagement and thus enhance the immune response. Specific types of NPs are useful in delivering the antigen into the cytoplasm of the target cell. Packaging of antigens within NPs enhances their protection against enzymatic or proteolytic cleavage. (C) NPs can pass through the lymphatic drainage system and activate APCs within the lymph nodes. (D) NPs aid the DC–T cell interaction that is necessary to boost the downstream immune response. They activate dendritic cells and influence the release of pro- and anti-inflammatory cytokines. (E) Antibody production by plasma B cells and the differentiation, maturation, and activation of lymphocytes and monocytes is also positively influenced by NP-mediated vaccine delivery. Abbreviations: APC, antigen-presenting cell; DC, dendritic cell; LN, lymph node; NP, nanoparticle; NV, nanovaccine.

Figure 2

Comparative account of loading strategies of nanoparticles to boost the immune response. Different modes of loading of the nanomaterials to enhance immune responses. It was previously reported that encapsulation of antigens tends to provide better protection [89], better MHC I activation [92], and better nuclear delivery [100] than surface immobilization. Covalently attached antigens can generate stronger immune responses than non-covalently tethered antigens [79]. Liposomes can elicit stronger antibody responses than other nanoparticle systems [57,93., 94., 95., 96., 97., 98., 99.]. Abbreviations: APC, antigen-presenting cell; OVA, ovalbumin; PLGA, polylactide-co-glycolic acid.

Figure 3

Mechanism of action of nanovaccines. Different types of antigens conjugated to nanoparticles (NPs) stimulate antigen-presenting cells (APCs) to process and present the antigens in different manners. Some antigens are received by mannose receptors, some are degraded within the APCs and the antigenic peptide fragments are then presented via MHC I (to activate CD8 T cells) or via MHCII (to activate CD4 T cells). APCs (like dendritic cells and T cells) also secrete cytokines in the process. This release of cytokines alters the cytokine milieu and shapes either pro- or anti-inflammatory responses. Clonal expansion of the activated T cells and B cells leads to boosting of the immune response. Activated plasma B cells release antibodies in response to the specific antigen conjugated to the NPs. Some cells remain as memory cells to provide an immediate antibody response in the case of natural antigenic challenge. The annotations adjacent to individual nanovaccines highlight mechanistic steps taking place in APCs or downstream immune response column and illustrate the diverse mechanisms of action of individual nanovaccines. Abbreviation: LPS, lipopolysaccharide.

Figure 4

Strategies for the development of nanovaccines against SARS-CoV-2. (A) The spike protein S that is present at the surface of the virus is unique for SARS-CoV-2 and has been used as a vaccine target by different laboratories. Nanovaccines comprise S protein mRNA. although the corresponding DNA sequence can also used. S proteins are often broken down into fragments that can also be used as antigens. (B) (i) The Astrazeneca, Sputnik V, and Johnson & Johnson vaccines use conventional adenovirus-mediated DNA transfer method to express SARS-CoV-2 S protein at the site of inoculation. (ii) The Moderna and Pfizer vaccines introduce S mRNA by means of lipid nanoparticles, leading to local synthesis. (iii) Novavax contains S protein embedded in a nanoparticle system, whereas (iv) Bharat Biotech and Sinopharm used a conventional inactivated whole virus vaccine. Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.

Figure I

Future nanovaccines.