Nickel-Chelating Nanolipoprotein Particles (NiNLPs) as Versatile Platforms for Vaccine Development
N.O. Fischer, C.D. Blanchette, P.W. Mason, P.D. Hoeprich
Lawrence Livermore National Laboratory, US
Keywords: nanolipoprotein particles, vaccine, antigen, West Nile virus
Abstract:Novel approaches to accelerate vaccine development are needed to protect against threats to human health and national security such as emerging infectious pathogens, biothreat agents, and multidrug-resistant pathogens. Recombinant proteins provide a number of important benefits currently lacking in traditional vaccine candidates, including increased safety, better formulation characterization, fewer side-effects, and potential for multivalent or broad-spectrum vaccination. Particulate delivery systems and immunostimulatory adjuvants are often important components of recombinant subunit protein vaccines, primarily to enhance immunogenicity. We are interested in developing a universal platform for the delivery and presentation of any protein antigen while also incorporating adjuvants to enhance the host’s immune response. To accomplish this, we have developed nickel-chelating nanolipoprotein particles (NiNLP) as universal vaccine platforms for three main reasons: 1) nickel-chelating ability of NiNLPs allows facile conjugation of any polyhistidine (His)-tagged protein, 2) NiNLPs can act as particulate delivery systems to enable clustered and oriented presentation of antigens, and 3) the formation of NiNLPs is amenable to the incorporation of secondary adjuvants to enhance immune response. Conjugation of myriad His-tagged proteins to NiNLPs has been accomplished. Furthermore, NiNLPs functionalized with a His-tagged surface antigen from West Nile virus provides substantial protection against a live viral challenge in mice.