Advances in Oral Subunit Vaccine Design

Abstract

Many pathogens invade the host at the intestinal surface. To protect against these enteropathogens, the induction of intestinal secretory IgA (SIgA) responses is paramount. While systemic vaccination provides strong systemic immune responses, oral vaccination is the most efficient way to trigger protective SIgA responses. However, the development of oral vaccines, especially oral subunit vaccines, is challenging due to mechanisms inherent to the gut. Oral vaccines need to survive the harsh environment in the gastrointestinal tract, characterized by low pH and intestinal proteases and need to reach the gut-associated lymphoid tissues, which are protected by chemical and physical barriers that prevent efficient uptake. Furthermore, they need to surmount default tolerogenic responses present in the gut, resulting in suppression of immunity or tolerance. Several strategies have been developed to tackle these hurdles, such as delivery systems that protect vaccine antigens from degradation, strong mucosal adjuvants that induce robust immune responses and targeting approaches that aim to selectively deliver vaccine antigens towards specific immune cell populations. In this review, we discuss recent advances in oral vaccine design to enable the induction of robust gut immunity and highlight that the development of next generation oral subunit vaccines will require approaches that combines these solutions.

Bacterial Ghosts of Pseudomonas aeruginosa as a Promising Candidate Vaccine and Its Application in Diabetic Rats

“…Cimetidine (50 mg/kg) administered intravenously to lower gastric acid output in the stomach (in rabbit) and 15 mL of 5% sodium bicarbonate injected twice intragastrically to neutralize stomach acid were utilized by Xian et al (2020) [44]. For example, cellulose acetate phthalate (Eudragit) is frequently employed as a polymer film to protect a capsulated vaccination since it is insoluble at low pH in the stomach but dissolves rapidly at higher pH in the gut, depending on the type of Eudragit used [45,46]. However, increasing the number of BGs utilized and using successful repeated boosters that allow for proper immune response are still the favored approaches [12,16].…”

Mucosal Vaccination Against Periodontal Disease: Current Status and Opportunities

“…The oral route is the most convenient and patient-accepted route of administration ( 133 ) and allows dissemination of antigen-specific lymphocytes to other mucosal tissues, such as the gastrointestinal, oral, genital, and respiratory mucosa. On the other hand, oral vaccines must overcome the gastric acid and digestive enzymes, the epithelial barrier, and the tolerogenic immune responses in order to successfully deliver antigens to the gut-associated lymphoid tissue and elicit protective immunity ( 134 , 135 ).…”

A review of the antiviral activity of Chitosan, including patented applications and its potential use against COVID‐19

“…In addition to chitosan's proven antimicrobial and antiviral properties, it also has a role in the development of antiviral vaccines due to its adjuvant properties (Van der Weken et al, 2021). Additionally, the use of chitosan in the development of nanoparticle vaccines to treat arbovirus disease has been suggested by de Souza et al (2021).…”