Application of nanotechnologies for improved immune response against infectious diseases in the developing world

Abstract

There is an urgent need for new strategies to combat infectious diseases in developing countries. Many pathogens have evolved to elude immunity and this has limited the utility of current therapies. Additionally, the emergence of co-infections and drug resistant pathogens has increased the need for advanced therapeutic and diagnostic strategies. These challenges can be addressed with therapies that boost the quality and magnitude of an immune response in a predictable, designable fashion that can be applied for wide-spread use. Here, we discuss how biomaterials and specifically nanoscale delivery vehicles can be used to modify and improve the immune system response against infectious diseases. Immunotherapy of infectious disease is the enhancement or modulation of the immune system response to more effectively prevent or clear pathogen infection. Nanoscale vehicles are particularly adept at facilitating immunotherapeutic approaches because they can be engineered to have different physical properties, encapsulated agents, and surface ligands. Additionally, nanoscaled point-of-care diagnostics offer new alternatives for portable and sensitive health monitoring that can guide the use of nanoscale immunotherapies. By exploiting the unique tunability of nanoscale biomaterials to activate, shape, and detect immune system effector function, it may be possible in the near future to generate practical strategies for the prevention and treatment of infectious diseases in the developing world.

Fig. 1

Disease burden of infectious disease in low income countries; statistics adapted from the World Health Organization [1]. A. Infectious disease burden distribution by income group, as measured by disability-adjusted life years (DALYs). A DALY measures years of healthy life lost due to premature mortality. Income levels are based on the gross national income per capita, and are grouped as low income (US $10,066) nations. B. Mortality due to infectious diseases in low income nations (

Fig. 2

Immune system interactions. The immune system consists of several cellular interactions that lead to different functional responses by different immune cells. Numerous cell surface receptor–ligand interactions, cytokines, and inflammatory molecules coordinate and affect the immune response. Antigen presenting cells such as dendritic cells can interact with CD8 T cells to stimulate cellular (cytolytic) immune responses, or with CD4 T cells to prime humoral (antibody) based responses. A CD4 T cell can differentiate into a variety of effector subsets, which include those that stimulate B cells to produce antibodies or those that help activate other immune clearance and regulatory processes.

Fig 3

Human body entry routes for infectious pathogen. Pathogens can enter the body via a cutaneous/blood route or through the mucosal surfaces. The cutaneous/blood route involves pathogen penetration through the skin and into the blood stream. This cutaneous penetration can occur by insect bites (such as mosquitoes, sandflies, and flies), through the use of contaminated medical supplies, or when the pathogen directly penetrates through the epidermis. The mucosal surface consists of three main tracts: the respiratory, the oral (gastrointestinal), and the urogenital (reproductive). The ocular route is also another mucosal surface. Some pathogens, such as HIV and hepatitis B and C, can enter the body through more than one route.

Fig. 4

Nanoparticles can be modified in many ways to achieve beneficial transport (pharmacokinetic) and immunomodulatory (pharmacodynamic) effects. The composition of the nanoparticle can be fabricated from different materials which control several aspects about nanoparticle transport and pharmacokinetics. The nanoparticle material composition typically controls the loading and release rate of encapsulants from the nanoparticle and can also influence the organ and intracellular trafficking of the particle. Furthermore, certain nanoparticle material formulations can stabilize or protect the encapsulated compound from physiological caustic environments in vivo and possibly from ambient environmental conditions during transport of the therapeutic to remote settings. The addition of targeting and immune stimulatory ligands to the particle surface can enhance cell and tissue specific targeting of nanoparticles. These ligands can also have a direct pharmacodynamic effect by triggering immune responses through cell-surface receptor mediated signaling events, such as when nanoparticle surface associated PAMPs trigger TLRs. Finally, the choice of encapsulant within the nanoparticles can have potent immunomodulatory effects.