Table 2 The efficacy, mechanisms, and limitations of oral vaccine platforms

Probiotic-based oral vaccines

Oral Lactobacillus plantarum GUANKE (LPG) combined with SARS-CoV-2 vaccines ⁹⁹.

LPG mobilized immune responses in the mucosal and systemic compartments; in particular, gut-spleen and gut-lung immune axes were observed.

The appropriate strains and doses of probiotic still need to be determined.

Coating Escherichia coli with yeast capsule containing β-glucan ¹⁰².

They protected from gastrointestinal exposure; delivered Escherichia coli to PP to induce mucosal immunity.

The camouflaging efficiency is unstable and affected by many factors; Differences between batches.

Modulation of gut microbiota-based oral vaccines

Oral inulin gel combined with α-PD-1 IgG immunotherapy¹⁰⁶

They increased the abundance of key commensal microbiota and short-chain fatty acid metabolites, leading to enhanced CD8⁺T cell responses.

Antigen capsulation efficiency; Differences between batches.

PLGA-loaded antimicrobial peptide microspheres¹⁰⁷

They enhanced the abundance of beneficial bacteria in the intestinal tract while simultaneously reducing the prevalence of pathogenic bacteria.

Bacillus Calmette-Guérin (BCG) vaccine¹¹²

Oral BCG induced stronger mucosal immunity and trafficked to distant mucosal tissues.

Differentiation and balance of antigen-specific and nonspecific immunity.

Engineered microbial system-based oral vaccines

E. coli strain with a SARS-CoV-2 spike protein-encoding plasmid¹²²

They elicited systemic and mucosal immunity. The surface expression of viral epitopes on E. coli can extend the half-life of these epitopes, while simultaneously acting as adjuvants to enhance the overall immune response.

Maintaining the viability of sufficient numbers of bacteria, the modification efficiency of functional groups, the protection of functional groups, the expression efficiency of target antigens, the neutralization of toxicity, the safety and ethical considerations.

Lactobacillus acidophilus was used to deliver a protective antigen from Bacillus anthracis¹²⁶

They induced robust protective immunity in mice. Lactobacillus also exert an effective bacterial adjuvant effect.

Oral spore-based nanoparticle generator modified with deoxycholic acid ¹²⁸.

They penetrated epithelial cells to increase basolateral drug release and promote cancer therapy.

VP1 chimeric antigens of bacterial ghosts¹³⁴

They elicited humoral and mucosal immune responses. Bacterial ghosts possess carrier and adjuvant property.

OMVs derived from genetically engineered E. coli ¹³⁹.

OMVs can overcome the intestinal epithelial barrier and be internalized by DCs in the lamina propria of the intestine to induce anti-tumor immunity.