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Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity

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  • Theme: Pioneering Pharmaceutical Science by Emerging Investigators
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Abstract

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin319–340—OVABT) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine—Pam2C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications.

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Acknowledgements

We thank Professor Thomas Phillips, Professor Jeffrey Adamovicz, Alexis Dadelahi, and Dr. Curtis Pritzl for their useful input on this work. We also thank Biolegend technical support team for their assistance on flow cytometry and cytokine multiplex assays.

Funding

This work is supported by the University of Missouri start-up funding, the University of Missouri research council board, and the PhRMA Foundation.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Missouri, W2027 Lafferre Hall, 416 S. 6th Street, Columbia, Missouri, 65211, USA

    Rui Zhang, Josiah D. Smith, Caitlin N. Leeper, Xiaolei Li, Logan D. Morton & Bret D. Ulery

  2. Department of Biochemistry, University of Missouri, Columbia, Missouri, 65211, USA

    Jake S. Kramer

  3. Department of Bioengineering, University of Missouri, Columbia, Missouri, 65211, USA

    Brittany N. Allen & Bret D. Ulery

  4. Molecular interactions Core, University of Missouri, Columbia, Missouri, 65211, USA

    Fabio Gallazzi

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  1. Rui Zhang
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Correspondence to Bret D. Ulery.

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Zhang, R., Kramer, J.S., Smith, J.D. et al. Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity. AAPS J 20, 73 (2018). https://doi.org/10.1208/s12248-018-0233-6

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