Demystifying particle-based oral vaccines

ABSTRACT

Introduction: The oral route of vaccination is pain- and needle-free and can induce systemic and mucosal immunity. However, gastrointestinal barriers and antigen degradation impose significant hurdles in the development of oral vaccines. Live attenuated viruses and bacteria can overcome these barriers but at the risk of introducing safety concerns. As an alternative, particles have been investigated for antigen protection and delivery, yet there are no FDA-approved oral vaccines based on particle-based delivery systems. Our objective was to discover underlying determinants that can explain the current inadequacies and identify paradigms that can be implemented in future for successful development of oral vaccines relying on particle-based delivery systems.

Areas covered: We reviewed literature related to the use of particles for oral vaccination and placed special emphasis on formulation characteristics and administration schedules to gain an insight into how these parameters impact production of antigen-specific antibodies in systemic and mucosal compartments.

Expert opinion: Despite the long history of vaccines, particle-based oral vaccination is a relative new field with the first study published in 1989. Substantial variability exists between different studies with respect to dosing schedules, number of doses, and the amount of vaccine per dose. Most studies have not used adjuvants in the formulations. Better standardization in vaccination parameters is required to improve comparison between experiments, and adjuvants should be used to enhance the systemic and mucosal immune responses and to reduce the number of doses, which will make oral vaccines more attractive.

KEYWORDS:

• Delivery
• mucosal
• oral vaccine
• particles
• pollen
• sporopollenin

Article highlights

• There are only four oral vaccines approved and three of them are based on live pathogens, which have potential safety risks.

• To develop safer oral vaccines based on proteins, peptides, and DNA/RNA as antigens, particles are often used as delivery systems.

• The first paper on the use of particles for in vivo oral vaccinations was published in 1989, and since then just about 162 papers have been published.

• Better standardization of vaccination schedules and doses is required so that immune responses across different studies can be compared

• Adjuvants should be developed and used for oral formulations to improve vaccine-induced immunity.

Declaration of interest

H Singh Gill and P Gonzalez-Cruz are co-inventors on a patent related to the development of pollen grains for oral vaccines. This potential conflict of interest has been disclosed and is managed by Texas Tech University. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary Material

Supplemental data for this article can be accessed here.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research was supported in parts by the National Institutes of Health (NIH) [grant number DP2HD075691] (HSG), and endowment funds of Whitacre Endowed Chair in Science and Engineering (HSG).