Colocalized delivery of adjuvant and antigen using nanolipoprotein particles enhances the immune response to recombinant antigens

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[1] Fischer, Nicholas O.
[2] Rasley, Amy
[3] Corzett, Michele
[4] Hwang, Mona H.
[5] Hoeprich, Paul D.
[6] Blanchette, Craig D.
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Hoeprich, P.D. (hoeprich2@llnl.gov) | 1600年 / American Chemical Society卷 / 135期
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Subunit antigen-based vaccines can provide a number of important benefits over traditional vaccine candidates; such as overall safety. However; because of the inherently low immunogenicity of these antigens; methods for colocalized delivery of antigen and immunostimulatory molecules (i.e; adjuvants) are needed. Here we report a robust nanolipoprotein particle (NLP)-based vaccine delivery platform that facilitates the codelivery of both subunit antigens and adjuvants. Ni-chelating NLPs (NiNLPs) were assembled to incorporate the amphipathic adjuvants monophosphoryl lipid A and cholesterol-modified CpG oligodeoxynucleotides; which can bind His-tagged protein antigens. Colocalization of antigen and adjuvant delivery using the NiNLP platform resulted in elevated antibody production against His-tagged influenza hemagglutinin 5 and Yersinia pestis LcrV antigens. Antibody titers in mice immunized with the adjuvanted NLPs were 5-10 times higher than those observed with coadministration formulations and nonadjuvanted NiNLPs. Colocalized delivery of adjuvant and antigen provides significantly greater immune stimulation in mice than coadministered formulations. © 2013 American Chemical Society;
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