Oral delivery of nanoparticle-based vaccines

Abstract

Most infectious diseases are caused by pathogenic infiltrations from the mucosal tract. Therefore, vaccines delivered to the mucosal tissues can mimic natural infections and provide protection at the first site of infection. Thus, mucosal, especially, oral delivery is becoming the most preferred mode of vaccination. However, oral vaccines have to overcome several barriers such as the extremely low pH of the stomach, the presence of proteolytic enzymes and bile salts as well as low permeability in the intestine. Several formulations based on nanoparticle strategies are currently being explored to prepare stable oral vaccine formulations. This review briefly discusses several molecular mechanisms involved in intestinal immune cell activation and various aspects of oral nanoparticle-based vaccine design that should be considered for improved mucosal and systemic immune responses.

Keywords::

• adjuvant
• bilosomes
• liposomes
• M-cells
• mucosal vaccine
• nanoparticle-based vaccine
• oral vaccine
• virus-like particle

Financial & competing interests disclosure

This work was supported by National Health and Medical Research Council (NHMRC), Australia. The contents are solely the responsibility of authors and do not necessarily represent the official views of NHMRC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The main challenges associated with oral vaccine delivery are sufficient protection of the integrity of the antigens and effective transportation across the intestinal epithelium.

• Efficacy of oral vaccines is mostly hampered by the low population of microfold-cells (M-cells) in the intestines.

• An alternative novel targeted delivery system is sought for effective delivery of oral vaccines to M-cells, intestinal dendritic cells and enterocytes.

• Several polymer and lipid-based nanocarriers have shown potential to enhance the immunogenicity of oral vaccines; however, there is no clear specific mechanism identified to show how these carriers promote enhanced mucosal and immune responses.

• Certain modifications of existing nanoparticulate delivery systems may drastically change stability/efficacy of vaccines. For example, bilosomes in contrast to liposomes have shown greatly improved stability in the gastrointestinal tract and during production/storage.

• Further developments in nanoparticle vaccines should concentrate on simple and robust design of the formulations for easy scale-up and commercialization.

Notes