Selective Inhibition of Systemic Anti-OVA IgE Production in Response to Oral Pre-Treatment with OVA-Liposome Conjugates

Abstract

Background: We have previously reported that intraperitoneal injection with OVA-liposome conjugates induces OVA-specific and IgE-selective unresponsiveness in mice. Methods: In the present study, the effects of oral pre-treatment with OVA-liposome conjugates or with plain OVA solution on anti-OVA IgG antibody production were investigated in mice after subsequent immunization with alum-adsorbed OVA. Control mice received only the immunization. Results: The levels of serum anti-OVA IgG antibody in mice receiving oral administration of OVA-liposome were comparable to those in the control mice. However, in mice receiving oral administration of the same dose of plain OVA, levels of serum anti-OVA IgG antibody were significantly lower than those in control mice. Surprisingly, anti-OVA IgE antibody production was completely inhibited in mice receiving oral administration of OVA-liposome conjugates. Splenic CD4⁺ T cells of mice receiving oral administration of OVA-liposome and those of control mice produced comparable levels of cytokines, while those of mice receiving oral administration of plain OVA solution produced significantly lower levels of cytokines than those in the other two groups. Conclusion: Orally administered OVA-liposome did not affect anti-OVA IgG production but did inhibit anti-OVA IgE antibody production, while orally administered OVA solution inhibited production of both IgG and IgE antibodies. These results suggest that antigen-liposome conjugates can possibly be orally administered in order to control antigen-specific IgE antibody production, without affecting IgG antibody production.

Improvement of sublingual immunotherapy efficacy with a mucoadhesive allergen formulation

“…[7][8][9][10][11] Although SLIT has been in clinical use in human beings for more than 15 years, very few experiments have been conducted in animal models. [17][18][19] Most existing animal models are performed in a prophylactic setting (ie, SLIT conducted before or in parallel with allergen challenge), whereas in human beings, SLIT is always used therapeutically.…”

“…6 Also, the use of adjuvants as well as mucosal formulations to improve current sublingual vaccines has been totally unexplored. Whereas various murine models are available to test new strategies of allergen-specific immunotherapy conducted via the parenteral, nasal, or oral routes, [7][8][9][10][11] it has been a challenge to develop such an animal model for sublingual immunization, largely because of difficulty controlling and documenting the level of antigen exposure to the sublingual immune system.…”

Liposomes with Differential Lipid Components Exert Differential Adjuvanticity in Antigen−Liposome Conjugates via Differential Recognition by Macrophages

“…We previously reported that antigens chemically coupled to the surface of liposomes induced antigen-specific IgG but not IgE antibody production (15). This IgE-selective unresponsiveness was induced by antigen-liposome conjugates regardless of the coupling procedure of the antigen and liposomes (16), of the antigens used for the coupling with liposomes (17), or of the route of inoculation (i.e., intraperitoneal (15) or intranasal (18)). The inducibility of antigen-specific IgG antibody production by antigen-liposome conjugates varied among the liposome preparations used for the production of antigen-liposome conjugates; the greater the membrane mobility in liposomes, the more antibody production induced by antigenliposome conjugates (19).…”