Naturally Occurring Lipid A based Adjuvants

基于天然脂质 A 的佐剂

• 批准号: 8236987
• 负责人: Samuel I Miller
• 金额: $ 17.52万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8236987
• 关键词: Adjuvant; Cells; Centers of Research Excellence; Characteristics; Development; Emerging Communicable Diseases; Endotoxins; Funding Mechanisms; Goals; Gram-Negative Anaerobic Bacteria; Human; Immune; Immune response; Immunity; In Vitro; Legal patent; Lipid A; Lipids; Lipopolysaccharides; Modeling; Mus; Porphyromonas gingivalis; Research; Research Personnel; Structure; Testing; Toxic effect; Vaccine Adjuvant; Vaccines; Virus; aluminum sulfate; base; biodefense; immunogenic; improved; microbial; monophosphoryl lipid A; mouse model; novel; novel vaccines; pathogen; prophylactic; tumor

There is a need for more effective vaccine adjuvants. Historically alum has been the only approved adjuvant for human use and has been effective and safe when administered with whole-cell or virus-based vaccines. However increased recognition of bacterial pathogenic mechanisms has led to the development of newer vaccines to pathogens that contain a more defined, microbial component selective composition that often is less immunogenic. Simultaneously, adjuvant research has advanced with the identification of monophosphoryl lipid A (MPL), a vaccine adjuvant that can safely boost the immune response. MPL was obtained by selective structural degradation of toxic bacterial lipopolysaccharide (LPS), often referred to as endotoxin. MPL, as a modified LPS, retained its immunogenic characteristics while significantly reducing its toxic effects. However, LPS obtained from several species of anaerobic gram negative bacteria have been shown to contain a naturally occurring low toxicity lipid A. Recently, we demonstrated that two naturally occurring low toxicity lipid A's obtained from Porphyromonas gingivalis can boost the immune response and are effective vaccine adjuvants in two different tumor models in mice (Porphyromonas gingivalis 1435/1449 LPS as an immune modulator, Patent US2007/0134170A1). In this proposal our hypothesis is: "Naturally occurring low toxicity lipid A's represent a new class of vaccine adjuvants". We will test this hypothesis by isolating and characterizing low toxicity lipid A's (LT lipid A) from several species of anaerobic gram negative bacteria (Aim 1). We will then examine their adjuvant potential in in vitro (Aim 2) and mouse models of non specific (Aim 3) and specific immunity (Aim 4). These studies will determine if naturally occurring LT lipid A's represent a new class of safe and effective vaccine adjuvants.

需要更有效的疫苗佐剂。历史上明矾是唯一被批准的佐剂