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.

Figure 1.

Historical patterns found in oral vaccine research using particles as a delivery system. A. distribution of articles published per year. b. relative frequency of diseases studied. C. animals used in oral vaccine testing.

Figure 2.

Antigen types used in oral vaccines using particles. A. frequency of types of molecules used as antigens. B. categorization and frequency of use of specific antigens. abbreviations are provided in supplementary Table-1.

Figure 3.

Vaccine formulation and schedule characteristics. A. frequency of amount of vaccine given per oral administration. B. distribution of vaccine amount for specific diseases against which oral vaccines were tested. C. last day of reported immune response for in vivo studies that tested oral vaccines.

Figure 4.

Commonly used particle carriers in oral vaccines. A. particle size range frequency in research articles for oral vaccines. B. types of particle carriers used to transport oral vaccines. C-E: diseases treated with oral vaccines using the most frequent particle carriers: C. chitosan particles, D. PLGA particles, and E. virus-like particles.

Figure 5.

Adjuvants added to particle systems. A. frequency of articles using specific adjuvants for oral vaccines with particles. inset figure shows the distribution of articles that incorporate adjuvants in their formulations. B. dose amount for each adjuvant that was added to vaccine formulations.

Figure 6.

Oral vaccine parameters and associated immune response. A. correlation of oral vaccine formulation parameters with immune responses reported in endpoint titers. B. minimum, maximum, and means of end point titers in systemic and different mucosal compartments.