Nanolipoprotein particles as vaccine platforms for co-localization of adjuvants and subunit antigens (106.10)

Abstract

Abstract Subunit vaccines provide a number of important benefits over traditional vaccine candidates, such as overall safety. However, these antigens require immunostimulatory adjuvants to generate the appropriate adaptive immune response. We hypothesize that the efficacy of subunit antigens will be enhanced if co-localized with adjuvant during delivery in a single delivery platform. Thus, our goal is to develop a robust vaccine delivery platform that will allow for the co-delivery of both subunit antigens and adjuvants using nanolipoprotein particles (NLPs). NLPs are discoidal HDL analogs comprised of lipid bilayers stabilized by scaffold proteins. These biocompatible, nanoscale particles can be assembled to incorporate nickel-chelating lipids to form nickel-chelating NLPs (NiNLPs). Thus, any His-tagged antigens can be conjugated to the NiNLPs. The amphipathic adjuvants monophosphoryl Lipid A (MPLA) and cholesterol-modified CpGs (Chol-CpGs) were anchored to the lipid bilayer of the NiNLPs. His-tagged influenza hemagglutinin 5 was conjugated to adjuvant:NiNLPs and injected into mice. Antibody titers increased 32 and 8 fold (MPLA and CpG, respectively) compared to co-administered formulations. Also, the immune response was skewed towards a Th1 response, with up to 16-fold increases in IgG2a:IgG1 ratios. Our findings demonstrate that co-localized delivery of adjuvant with antigens provides significantly greater immune stimulation in mice compared to co-administered formulations.