Robust IgG responses to nanograms of antigen using a biomimetic lipid-coated particle vaccine

New subunit vaccine formulations with increased potency are of interest to improve immune responses against poorly immunogenic antigens, to avoid vaccine shortages in pandemic situations, and to promote dose-sparing of potent adjuvant molecules that can cause unacceptable side effects in prophylactic vaccination. Here we report strong class-switched, high avidity humoral immune responses elicited by a vaccine system based on poly(lactide-co-glycolide) micro-or nano-particles enveloped by PEGylated phospholipid bilayers, with protein antigens covalently anchored to the lipid surface and lipophilic adjuvants inserted in the bilayer coating. Strikingly, these particles elicited high endpoint antigen-specific IgG titers (>10(6)) sustained for over 100 days after two immunizations with as little as 2.5 ng of antigen. At such low doses, the conventional adjuvant alum or the molecular adjuvants monophosphoryl lipid A (MPLA) or alpha-galactosylceramide (alpha GC) failed to elicit responses. Co-delivery of antigen with MPLA or alpha GC incorporated into the particle bilayers in a pathogen-mimetic fashion further enhanced antibody titers by similar to 12-fold. MPLA provided the highest sustained IgG titers at these ultra-low antigen doses, while alpha GC promoted a rapid rise in serum IgG after one immunization, which may be valuable in emergencies such as disease pandemics. The dose of alpha GC required to boost the antibody response was also spared by particulate delivery. Lipid-enveloped biodegradable micro-and nano-particles thus provide a potent dose-sparing platform for vaccine delivery. (C) 2011 Published by Elsevier B.V.