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NPJ Vaccines. 2019 Jan 3;4:1. doi: 10.1038/s41541-018-0094-0. eCollection 2019.

Reprogramming the adjuvant properties of aluminum oxyhydroxide with nanoparticle technology.

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1Infectious Disease Research Institute, 1616 Eastlake Avenue East, Suite 400, Seattle, WA 98102 USA.
2Department of Global Health, University of Washington, 1510 San Juan Road, Seattle, WA 98195 USA.
3Unit of Surface, Process and Formulation, Division of Bioscience and Materials, RISE Research Institutes of Sweden, Drottning Kristinas Väg 45, Box 5607, SE 11486 Stockholm, Sweden.


Aluminum salts, developed almost a century ago, remain the most commonly used adjuvant for licensed human vaccines. Compared to more recently developed vaccine adjuvants, aluminum adjuvants such as Alhydrogel are heterogeneous in nature, consisting of 1-10 micrometer-sized aggregates of nanoparticle aluminum oxyhydroxide fibers. To determine whether the particle size and aggregated state of aluminum oxyhydroxide affects its adjuvant activity, we developed a scalable, top-down process to produce stable nanoparticles (nanoalum) from the clinical adjuvant Alhydrogel by including poly(acrylic acid) (PAA) polymer as a stabilizing agent. Surprisingly, the PAA:nanoalum adjuvant elicited a robust TH1 immune response characterized by antigen-specific CD4+ T cells expressing IFN-γ and TNF, as well as high IgG2 titers, whereas the parent Alhydrogel and PAA elicited modest TH2 immunity characterized by IgG1 antibodies. ASC, NLRP3 and the IL-18R were all essential for TH1 induction, indicating an essential role of the inflammasome in this adjuvant's activity. Compared to microparticle Alhydrogel this nanoalum adjuvant provided superior immunogenicity and increased protective efficacy against lethal influenza challenge. Therefore PAA:nanoalum represents a new class of alum adjuvant that preferentially enhances TH1 immunity to vaccine antigens. This adjuvant may be widely beneficial to vaccines for which TH1 immunity is important, including tuberculosis, pertussis, and malaria.

Conflict of interest statement

The authors declare no competing interests.

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