Vaccine has been part of human fight against infectious diseases for more than two centuries. An adjuvant is often required for a vaccine or antigen to induce a strong immune response, making it a crucial component in vaccines. Aluminum salts, such as aluminum hydroxide, are widely used in various human vaccines. Before the recent approval of AS04, for decades, aluminum-containing adjuvants were the only approved vaccine adjuvant for human use in the United States. Even AS04 contains aluminum hydroxide. Despite their demonstrated favorable safety profile, aluminum salts can only weakly or moderately potentiate antigen-specific antibody responses, and is generally considered incapable of enhancing cellular immune responses. Therefore, there continues to be a need to search for safe and more potent vaccine adjuvants. Our long-term goal is to develop a safe vaccine adjuvant that is more potent than the traditional aluminum adjuvants. Recently we discovered that the adjuvant activity of the traditional aluminum hydroxide can be significantly enhanced by modifying one of the physical properties of the aluminum hydroxide suspension. These exciting findings point to the potential of this novel aluminum hydroxide formulation as a novel vaccine adjuvant. However, to fully appreciate the feasibility using this novel aluminum hydroxide-containing adjuvant in future human vaccine development, there is a critical need to further characterize its adjuvant activity and to assess its safety in animal models, and the present application is designed to address this critical need. Specifically, we will (i) characterie the immune responses induced by a protein antigen adsorbed on our novel aluminum hydroxide-containg adjuvant. Bacillus anthracis protective antigen protein will be used as a functional model antigen in this study to characterize the specific B cell and T cell responses induced;(ii) elucidate the mechanisms underlying the potent adjuvant activity of our novel aluminum hydroxide-containing adjuvant;and (iii) assess the safety/toxicity of our aluminum hydroxide-containing adjuvant. The most innovative aspect of our proposed research is to enhance the potency of the traditional aluminum hydroxide adjuvant and to overcome its limitations by an innovative physical modification. Our expected outcomes from this project are to thoroughly characterize the immune responses induced by antigens adsorbed on our new aluminum hydroxide-containing adjuvant and to preliminarily assess its safety profile in a rodent model. Moreover, we expect to understand why the adjuvant activity of traditional aluminum hydroxide can be favorably modulated by modifying one of its physical properties. Collectively, these outcomes will provide a sound scientific foundation for future development of this novel aluminum hydroxide-containing adjuvant into a safe and more potent human vaccine adjuvant, which can be used in developing new vaccines as well as re-formulating existing vaccines.
The proposed research is relevant to public health because the characterization and evaluation of a novel aluminum-containing vaccine adjuvant that overcomes the limitations of the traditional aluminum salts is expected to ultimately lead to the development of highly potent and safe vaccines to fight against infectious diseases. Therefore, the proposed research is relevant to the NIH's mission that pertains to the prevention and treatment of infectious diseases.
|Thakkar, Sachin G; Xu, Haiyue; Li, Xu et al. (2018) Uric acid and the vaccine adjuvant activity of aluminium (oxy)hydroxide nanoparticles. J Drug Target 26:474-480|
|Li, Xu; Hufnagel, Stephanie; Xu, Haiyue et al. (2017) Aluminum (Oxy)Hydroxide Nanosticks Synthesized in Bicontinuous Reverse Microemulsion Have Potent Vaccine Adjuvant Activity. ACS Appl Mater Interfaces 9:22893-22901|
|Xu, Haiyue; Ruwona, Tinashe B; Thakkar, Sachin G et al. (2017) Nasal aluminum (oxy)hydroxide enables adsorbed antigens to induce specific systemic and mucosal immune responses. Hum Vaccin Immunother 13:2688-2694|
|Thakkar, Sachin G; Ruwona, Tinashe B; Williams 3rd, Robert O et al. (2017) The immunogenicity of thin-film freeze-dried, aluminum salt-adjuvanted vaccine when exposed to different temperatures. Hum Vaccin Immunother 13:936-946|
|Xu, Haiyue; Li, Xu; Cui, Zhengrong (2017) Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles. Ruwona TB, Xu H, Li X, Taylor AN, Shi Y, Cui Z. Vaccine 2016;34:3059-67. Vaccine 35:1102-1103|
|Ruwona, Tinashe B; Xu, Haiyue; Li, Xu et al. (2016) Toward understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles. Vaccine 34:3059-3067|
|Ruwona, Tinashe B; Xu, Haiyue; Li, Junwei et al. (2016) Induction of protective neutralizing antibody responses against botulinum neurotoxin serotype C using plasmid carried by PLGA nanoparticles. Hum Vaccin Immunother 12:1188-92|
|Li, Xinran; Thakkar, Sachin G; Ruwona, Tinashe B et al. (2015) A method of lyophilizing vaccines containing aluminum salts into a dry powder without causing particle aggregation or decreasing the immunogenicity following reconstitution. J Control Release 204:38-50|
|Prasad, Leena Kumari; O'Mary, Hannah; Cui, Zhengrong (2015) Nanomedicine delivers promising treatments for rheumatoid arthritis. Nanomedicine (Lond) 10:2063-74|
|Zheng, Yuan-qiang; Naguib, Youssef W; Dong, Yixuan et al. (2015) Applications of bacillus Calmette-Guerin and recombinant bacillus Calmette-Guerin in vaccine development and tumor immunotherapy. Expert Rev Vaccines 14:1255-75|
Showing the most recent 10 out of 12 publications