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Reprogramming the adjuvant properties of aluminum oxyhydroxide with nanoparticle technology
Infectious Disease Research Institute, US; University of Washington, US.
Infectious Disease Research Institute, US.
Infectious Disease Research Institute, US.
Infectious Disease Research Institute, US.
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2019 (English)In: npj Vaccines, ISSN 2059-0105, Vol. 4, article id 1Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 4, article id 1
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Natural Sciences
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URN: urn:nbn:se:ri:diva-37007DOI: 10.1038/s41541-018-0094-0Scopus ID: 2-s2.0-85059532005OAI: oai:DiVA.org:ri-37007DiVA, id: diva2:1281051
Note

 Funding details: Bill and Melinda Gates Foundation; Funding details: Case Western Reserve University, CWRU; Funding details: Adhesives and Sealant Council, ASC; Funding details: U.S. Department of Health and Human Services, HHS, 4R01AI025038; Funding details: National Institute of Allergy and Infectious Diseases, NIAID; Funding details: National Institutes of Health, NIH; Funding details: OPP1130379; Funding details: OPP1055855; .

Available from: 2019-01-21 Created: 2019-01-21 Last updated: 2019-01-21Bibliographically approved

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Persson, KarinAhniyaz, Anwar

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