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NanoBio™ Nanoemulsion for Mucosal Vaccine Delivery

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Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines

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Abstract

Nanoemulsions (NEs) are high-energy oil-in-water emulsions smaller than 1,000 nm that disrupt the outer lipid membrane of pathogenic microbes [1–4]. Building on studies that demonstrated the potential of NE to prevent influenza infection [5], it was recognized that NE inactivated influenza virus generated greater immune responses than formalin inactivated influenza virus when administered intranasally [6]. Subsequent studies have demonstrated this material acts as a mucosal adjuvant with numerous antigens including recombinant anthrax protective antigen (PA) [7], killed-vaccinia virus [8], recombinant human immunodeficiency (HIV) gp120 [9], recombinant hepatitis B surface antigen (HBsAg) [10], and purified Burkholderia cenocepacia outer membrane protein (OMP) [11]. In addition, it was recognized that the surfactant in the NE is locked at the interface between the oil droplets and water and does not appear to denature proteins. This confers thermostability to the antigen [10, 12–14] and potentially allows for the elimination of the cold chain required for all currently available vaccines [15]. The mechanisms by which adjuvants enhance the immune response are starting to be elucidated and include improved antigen delivery as well as innate immune activation [16]. The NE adjuvant acts via both mechanisms as it enhances antigen uptake by dendritic cells (DCs) as well as activating Toll like receptors (TLR) 2 and 4; this enhances both humoral and cell-mediated Th1 and Th17 immune responses [17]. Importantly, NE mucosal adjuvant activity occurs without damaging the mucosal epithelium [10] and has been demonstrated to be safe and well tolerated in early phase human clinical trials (Stanberry, submitted). In this review, we will delineate the physical and chemical properties, mechanisms of activity, preclinical studies, and clinical experience available regarding mucosal NE adjuvants.

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Acknowledgments

We would like to thank the volunteers participating in the clinical trials as well as the large number of personnel that have worked on the development and testing of the NE adjuvants. These include, but are not limited to: Anna Bielinska, Susan Ciotti, Mary Flack, Stephen Gracon, Casey Johnson, Lyou-fu Ma, Paul Makidon, Andrzej Myc, David Peralta, Douglas Smith, and Paula Robinson. Funding sources include: Defense Advanced Research Project Agency (DARPA) contract #MDA 972-1-007 of the Unconventional Pathogen Countermeasures Program, National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, University of Chicago, award U54 AI57153, the Bill & Melinda Gates Foundation Grand Challenges in Global Health Initiative 37868, the Ruth Dow Doan Endowment, the Burroughs Welcome Fund, and the Michigan Nanotechnology Institute for Medicine and Biological Sciences.

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Authors and Affiliations

  1. NanoBio Corporation, 2311 Green Road, Ann Arbor, MI, USA

    Tarek Hamouda, Jakub Simon, Ali Fattom & James Baker

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  1. Tarek Hamouda
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  2. Jakub Simon
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  3. Ali Fattom
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  4. James Baker
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Correspondence to James Baker .

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  1. Novartis Vaccines Research, Cambridge, 02139, Massachusetts, USA

    Manmohan Singh

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Hamouda, T., Simon, J., Fattom, A., Baker, J. (2013). NanoBio™ Nanoemulsion for Mucosal Vaccine Delivery. In: Singh, M. (eds) Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-5380-2_13

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