Antigen-specific enhancement of natural human IgG antibodies to phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol-4-phosphate, cholesterol, and lipid A by a liposomal vaccine containing lipid A

摘要

Natural IgG antibodies (NA) to lipids are ubiquitously distributed in sera of healthy humans and are believed to serve beneficial functions. Although NA to lipids generally exhibit germ line or near germ line binding specificities, the antibodies commonly increase transiently in the acute phases of most, if not all, infectious diseases and may serve as a first line of defense. In order to determine whether similar anti-lipid antibodies can be induced by a vaccine in humans, we examined stored sera obtained from volunteers who had previously received a candidate vaccine to Plasmodium falciparum. The vaccine had consisted of liposomes that contained both the recombinant protein antigen and also contained monophosphoryl lipid A (MPLA) as an adjuvant. All of the pre-immune sera contained NA to one or more of the liposomal lipids in the vaccine: dimyristol phosphatidylcholine (DMPC), dimyristoyl phosphatidylglycerol (DMPG), cholesterol, and MPLA. After initial immunization, followed by a boost, increased levels of IgG antibodies to all of the liposomal lipids, especially DMPG and MPLA, were observed by ELISA. Antibodies to phosphatidylinositol-4-phosphate (PIP) above the normal pre-immune NA to PIP were also observed. Although PIP was not present in the immunizing liposomes, based on the adsorption of anti-PIP antibodies by DMPG the anti-PIP antibodies were thought to represent cross-reacting anti-DMPG antibodies. The immune response was apparently antigen-specific in that NA to unrelated lipids, other than PIP, that were not present in the liposomes, galactosyl ceramide and ganglioside GM1, were not increased by the immunization. We conclude that antibodies to DMPC, DMPG, PIP, cholesterol, and MPLA can be induced in humans by immunization with liposomes containing MPLA