Oral immunization against hepatitis B using bile salt stabilized vesicles (bilosomes)

Area of Science:

• Immunology
• Vaccinology
• Nanotechnology

Background:

• Parenteral hepatitis B vaccines primarily induce systemic immunity, often failing to elicit a robust mucosal antibody response.
• Oral immunization presents an attractive alternative but faces challenges like antigen degradation and potential immune tolerance induction.
• Bile salt stabilized vesicles (bilosomes) offer a potential solution for protecting antigens and facilitating transmucosal uptake.

Purpose of the Study:

• To develop and evaluate HBsAg-loaded bilosomes for oral immunization.
• To assess the ability of bilosomes to protect HBsAg from gastrointestinal degradation and promote mucosal uptake.
• To compare the immunogenicity of orally administered HBsAg bilosomes with intramuscularly administered HBsAg, focusing on both serum and mucosal antibody responses and determining optimal dosing.

Main Methods:

• Recombinant HBsAg-loaded bilosomes were prepared using a lipid cast film method.
• In vitro characterization included assessment of shape, size, antigen entrapment, and stability.
• In vivo studies in BALB/c mice involved oral administration of varying HBsAg bilosome doses and measurement of anti-HBsAg IgG and sIgA responses via ELISA.

Main Results:

• Fluorescence microscopy confirmed bilosome uptake by gut-associated lymphoid tissues (GALT).
• High-dose HBsAg bilosomes (50 microg) elicited serum anti-HBsAg IgG levels comparable to intramuscular administration of alum-adsorbed HBsAg (10 microg).
• Bilosomal preparations successfully induced measurable mucosal sIgA, a response absent with intramuscular vaccination.

Conclusions:

• Oral administration of HBsAg-loaded bilosomes effectively induces both systemic and mucosal antibody responses.
• Bilosomes provide a viable strategy for oral vaccination, achieving comparable serum antibody titers to parenteral routes at higher oral doses without inducing tolerance.
• This technology holds promise for developing more effective oral vaccines against hepatitis B and potentially other diseases.