Induction of immunity against experimental tuberculosis with mycobacterial mannophosphoinositides encapsulated in liposomes containing lipid A

Abstract Mycobacterial mannophosphoinositides (PIMs) encapsulated in liposomes made of egg phosphatidylcholine (EPC) and cholesterol (CH) (2:1.5 molar ratio) were able to induce humoral and delayed type hypersensitivity (DTH, foot-pad swelling reaction) responses in mice without the help of any carrier protein. Animals immunized with this glycophospholipid antigen demonstrated enhanced percent survival on intravenous challenge with virulent M. tuberculosis . On fractionation of PIMs, pentamannophosphoinositide (PIM₅) was found to induce higher antibody and DTH reaction and proved to be more immunoprotective than other fractions. Inclusion of lipid A as immunomodulator in liposomes containing PIMs or PIM₅ resulted in a significantly increased immune response. Further, mice immunized with PIMs or PIM₅ in lipid A-containing liposomes exhibited decreased mortality on challenge with M. tuberculosis H₃₇Rv, which was comparable to BCG vaccinated animals.