Colocalized Delivery of Adjuvant and Antigen Using Nanolipoprotein Particles Enhances the Immune Response to Recombinant Antigens
| Autor: | Nicholas O. Fischer, Michele Corzett, Amy Rasley, Paul D. Hoeprich, Mona H. Hwang, Craig D. Blanchette |
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| Rok vydání: | 2013 |
| Předmět: |
Pore Forming Cytotoxic Proteins
CpG Oligodeoxynucleotide Lipoproteins medicine.medical_treatment Monophosphoryl Lipid A Hemagglutinin Glycoproteins Influenza Virus Biochemistry Catalysis Mice Colloid and Surface Chemistry Immune system Adjuvants Immunologic Antigen Nickel medicine Animals LcrV Antigens Bacterial Vaccines Chemistry Immunogenicity Antibody titer General Chemistry Virology Molecular biology Recombinant Proteins Nanoparticles Adjuvant |
| Zdroj: | Journal of the American Chemical Society. 135:2044-2047 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja3063293 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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