Novel Oral Adjuvant for Dental Vaccines

产品说明：牙齿和牙龈的细菌感染通常会导致蛀牙和牙周病，但也可能导致严重的系统性疾病，如心内膜炎。疫苗具有预防传染病的潜力。抗原与称为“佐剂”的免疫刺激剂的共同施用通常是刺激保护性免疫而不是耐受性的发展所必需的，特别是在对口服抗原的应答中。菠萝蛋白酶是从菠萝茎中提取的蛋白酶的天然混合物。虽然大多数蛋白质的摄入导致免疫耐受，但我们的初步数据表明，菠萝蛋白酶在口服时产生强烈的全身免疫反应。因此，菠萝蛋白酶可作为诱导抗菠萝蛋白酶抗体的自佐剂。我们的数据表明，菠萝蛋白酶被抑制捕获的复合物与广谱蛋白酶抑制剂α-2-巨球蛋白（α-2M）。α-2M复合物被存在于抗原呈递细胞上的受体有效地摄取。我们证实，口服菠萝蛋白酶与α-2M相互作用，形成复合物，有效地诱导免疫反应。基于该假设，与菠萝蛋白酶共捕获在α-2M复合物中的抗原也应该是强免疫原性的。本研究的目的是调查菠萝蛋白酶的蛋白水解活性的作用，在诱导抗体反应对自身和共同管理的抗原，使用口服疫苗对小鼠的牙齿病原体。菠萝蛋白酶蛋白水解活性将通过抗酸剂中的制剂增加或通过还原和烷基化永久灭活。菠萝蛋白酶将口服给予与抗原混合或共价连接的小鼠。将测定针对菠萝蛋白酶和抗原的特异性血清IgG和唾液IgG和伊加抗体应答。如果这些研究证实了菠萝蛋白酶作为佐剂的潜力，则可以开发含有菠萝蛋白酶和相关抗原的混合物的制剂，用于定期施用作为“快速吞咽”疫苗，以诱导和维持针对牙科病原体的免疫力。

DESCRIPTION: Bacterial infections of the teeth and gingiva commonly cause tooth decay and periodontal disease, but may also cause serious systemic diseases such as endocarditis. Vaccines have a demonstrated potential to prevent infectious diseases. Co-administration of antigen with an immune stimulant called an "adjuvant" is usually necessary to stimulate the development of protective immunity rather than tolerance, particularly in response to oral antigens. Bromelain is a natural mixture of proteinases derived from pineapple stem. Although ingestion of most proteins results in immune tolerance, our preliminary data show that bromelain generates strong systemic immune responses when administered orally. Thus bromelain may serve as a self-adjuvant for induction of anti-bromelain antibodies. Our data show that bromelain is inhibited by trapping in complexes with the broad spectrum proteinase inhibitor alpha-2-macroglobulin (alpha-2M). Alpha-2M complexes are efficiently taken up by receptors that are present on antigen-presenting cells. We posit that proteolytically active bromelain given orally interacts with alpha-2M in vivo to form complexes that efficiently induce immune responses. Based upon this hypothesis, antigens co-trapped with bromelain in alpha-2M complexes should also be strongly immunogenic. The Aim of this study is to investigate the role of bromelain proteolytic activity in induction of antibody responses against itself and co-administered antigens, using an oral vaccine against Dental pathogens in mice. Bromelain proteolytic activity will be increased by formulation in antacid or permanently inactivated by reduction and alkylation. Bromelain will be administered orally to mice mixed with or covalently linked to antigen. Specific serum IgG and salivary IgG and IgA antibody responses against bromelain and antigen will be determined. If these studies confirm the potential of bromelain as an adjuvant, preparations containing bromelain and a mixture of relevant antigens could be developed for periodic administration as "swish and swallow" vaccines to induce and maintain immunity against Dental pathogens.