Nanoparticle-Based Vaccines Against Respiratory Viruses

Abstract

The respiratory mucosa is the primary portal of entry for numerous viruses such as the respiratory syncytial virus, the influenza virus and the parainfluenza virus. These pathogens initially infect the upper respiratory tract and then reach the lower respiratory tract, leading to diseases. Vaccination is an affordable way to control the pathogenicity of viruses and constitutes the strategy of choice to fight against infections, including those leading to pulmonary diseases. Conventional vaccines based on live-attenuated pathogens present a risk of reversion to pathogenic virulence while inactivated pathogen vaccines often lead to a weak immune response. Subunit vaccines were developed to overcome these issues. However, these vaccines may suffer from a limited immunogenicity and, in most cases, the protection induced is only partial. A new generation of vaccines based on nanoparticles has shown great potential to address most of the limitations of conventional and subunit vaccines. This is due to recent advances in chemical and biological engineering, which allow the design of nanoparticles with a precise control over the size, shape, functionality and surface properties, leading to enhanced antigen presentation and strong immunogenicity. This short review provides an overview of the advantages associated with the use of nanoparticles as vaccine delivery platforms to immunize against respiratory viruses and highlights relevant examples demonstrating their potential as safe, effective and affordable vaccines.

Keywords: immune response; mucosal sites; nanocarriers; nanovaccine; respiratory viruses.

Figure 1

Overview of the immune response in the upper respiratory tract. (A) Schematic view of different nanoparticles used for intranasal vaccination. (B) Mechanisms of NALTs immune responses in the upper respiratory tract. (1) Nanoparticles are transcytosed from the mucus layer into the nasal epithelial tissues by micro-fold cells (M cells) or passively diffuse through epithelial cell junctions. (2) Other nanoparticles are captured and internalized by DCs (dendritic cells) from their extension through epithelial junctions and by other APCs, such as B cells. (3) Cells that have encountered nanoparticles migrate to the nearest lymph node in order to activate naive T helper cells. Once activated, T helper cells activate B cells that have encountered the same antigen presented by nanoparticles. Activated B cells proliferate in the lymph node (B cell zone) and, once mature, enter systemic circulation in order to reach the inflammation site. IgA+ B cells locally differentiate into antibody-secreting plasma cells to produce IgA dimers. (4) IgA dimers are secreted via polymeric Ig receptor (pIgR) at the mucosal surface. NALT immune response induces long-lasting memory B and T cells able to trigger a rapid recall response.