Autor: |
Abucayon EG; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.; U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA., Belikow-Crovetto I; U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.; Oak Ridge Institute for Science and Education, Oak Ridge, TN 37831, USA., Hussin E; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.; U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA., Kim J; Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.; U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA., Matyas GR; U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA., Rao M; U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA., Alving CR; U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. |
Abstrakt: |
Particulate aluminum salts have long occupied a central place worldwide as inexpensive immunostimulatory adjuvants that enable induction of protective immunity for vaccines. Despite their huge benefits and safety, the particulate structures of aluminum salts require transportation and storage at temperatures between 2 °C and 8 °C, and they all have exquisite sensitivity to damage caused by freezing. Here, we propose to solve the critical freezing vulnerability of particulate aluminum salt adjuvants by introducing soluble aluminum salts as adjuvants. The solubility properties of fresh and frozen aluminum chloride and aluminum triacetate, each buffered optimally with sodium acetate, were demonstrated with visual observations and with UV-vis scattering analyses. Two proteins, A244 gp120 and CRM 197 , adjuvanted either with soluble aluminum chloride or soluble aluminum triacetate, each buffered by sodium acetate at pH 6.5-7.4, elicited murine immune responses that were equivalent to those obtained with Alhydrogel ® , a commercial particulate aluminum hydroxide adjuvant. The discovery of the adjuvanticity of soluble aluminum salts might require the creation of a new adjuvant mechanism for aluminum salts in general. However, soluble aluminum salts might provide a practical substitute for particulate aluminum salts as vaccine adjuvants, thereby avoiding the risk of inactivation of vaccines due to accidental freezing of aluminum salt particles. |