Nanoparticle Vaccines Against Infectious Diseases

Abstract

Due to emergence of new variants of pathogenic micro-organisms the treatment and immunization of infectious diseases have become a great challenge in the past few years. In the context of vaccine development remarkable efforts have been made to develop new vaccines and also to improve the efficacy of existing vaccines against specific diseases. To date, some vaccines are developed from protein subunits or killed pathogens, whilst several vaccines are based on live-attenuated organisms, which carry the risk of regaining their pathogenicity under certain immunocompromised conditions. To avoid this, the development of risk-free effective vaccines in conjunction with adequate delivery systems are considered as an imperative need to obtain desired humoral and cell-mediated immunity against infectious diseases. In the last several years, the use of nanoparticle-based vaccines has received a great attention to improve vaccine efficacy, immunization strategies, and targeted delivery to achieve desired immune responses at the cellular level. To improve vaccine efficacy, these nanocarriers should protect the antigens from premature proteolytic degradation, facilitate antigen uptake and processing by antigen presenting cells, control release, and should be safe for human use. Nanocarriers composed of lipids, proteins, metals or polymers have already been used to attain some of these attributes. In this context, several physico-chemical properties of nanoparticles play an important role in the determination of vaccine efficacy. This review article focuses on the applications of nanocarrier-based vaccine formulations and the strategies used for the functionalization of nanoparticles to accomplish efficient delivery of vaccines in order to induce desired host immunity against infectious diseases.

Keywords: antigens; human diseases; nanoparticles; targeted vaccine delivery; vaccine development.

Figure 1

Schematic representation of the nanocarriers. Antigen can be conjugated to the nanoparticles surface or incapsulated into core of the particles. Decoration of the nanoparticles surface with targeting molecules (e.g., antibodies, Fab-fragments, peptides, etc) could further increase the delivery of particles into the antigen presenting cells (APCs) to induce innate and adaptive immune responses.

Figure 2

Targeted delivery of antigenic molecules using surface engineered nanoparticles into the antigen presenting cells (APCs). Endogenously generated antigens are presented in complex with class I major histocompatibility complex (MHC I) on the membrane of APCs to CD8+ T lymphocytes. Following the interaction between MHC I and T-cell receptor (TCR) in presence of co-stimulatory molecules and cytokines the activated CD8+ cells kill the infected cells by inducing cytotoxicity. Also the antigens are presented on the APC surface by class II MHC molecules to the helper (CD4+) T cells. Subsequently, CD4+ cells activate B-cells that produce anti-microbial antibodies. Upon stimulation the adaptor proteins MyD88 (myeloid differentiation marker 88) and TIRAP (TIR domain containing adaptor protein) colocalize with TLR (toll-like receptor) allowing for activation of the NF-κB pathway and leading to the production of pro-inflammatory cytokines.