Oral Vaccine Formulations Stimulate Mucosal and Systemic Antibody Responses against Staphylococcal Enterotoxin B in a Piglet Model
Oral Vaccine Formulations Stimulate Mucosal and Systemic Antibody Responses against Staphylococcal Enterotoxin B in a Piglet Model
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DOI：
10.1128/cvi.00078-10
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发表时间：
2010-08-01
影响因子：
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通讯作者：
Piller, Kenneth J.
中科院分区：
文献类型：
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作者：
Inskeep, Tiffany K.;Stahl, Chad;Piller, Kenneth J.
尽管其有可能用作生物战或生物恐怖主义的制剂，但目前还没有针对葡萄球菌肠毒素B（SE B）的获批疫苗。已经开发了SEB的无毒突变形式;然而，由于天然SEB在啮齿动物中缺乏超抗原活性以及由于灵长类动物模型的限制，难以确定此类亚单位疫苗候选物的功效。由于猪对SEB的反应方式与人类受试者相似，因此我们利用该相关动物模型研究携带氨基酸变化L45R、Y89A和Y94A的SEB三重突变体的安全性和免疫原性。这种重组突变体SEB（rmSEB）在猪淋巴细胞培养中不具有超抗原活性。此外，rmSEB不能与天然SEB竞争结合猪白细胞。这些体外研究表明，rmSEB可能是一种安全的亚单位疫苗。为了测试这种可能性，用rmSEB制剂经口免疫的仔猪在接种方案期间没有经历食物消耗的显著减少并且没有体重减轻。在第0、7、14和24天用1 mg剂量的rmSEB口服疫苗接种导致到第36天血清IgG和粪便IgA水平与天然SEB交叉反应。令人惊讶的是，与仅使用免疫原的制剂相比，在含有rmSEB的疫苗制剂中包含霍乱毒素佐剂不会导致抗体应答增加。总之，这些研究为SEB的无毒形式作为疫苗的潜在用途提供了额外的证据。
Despite the potential for its use as an agent of biowarfare or bioterrorism, no approved vaccine against staphylococcal enterotoxin B (SEB) exists. Nontoxic, mutant forms of SEB have been developed; however, it has been difficult to determine the efficacy of such subunit vaccine candidates due to the lack of superantigen activity of native SEB in rodents and due to the limitations of primate models. Since pigs respond to SEB in a manner similar to that of human subjects, we utilized this relevant animal model to investigate the safety and immunogenicity of a triple mutant of SEB carrying the amino acid changes L45R, Y89A, and Y94A. This recombinant mutant SEB (rmSEB) did not possess superantigen activity in pig lymphocyte cultures. Furthermore, rmSEB was unable to compete with native SEB for binding to pig leukocytes. These in vitro studies suggested that rmSEB could be a safe subunit vaccine. To test this possibility, piglets immunized orally with rmSEB formulations experienced no significant decrease in food consumption and no weight loss during the vaccination regimen. Oral vaccination with 1-mg doses of rmSEB on days 0, 7, 14, and 24 resulted in serum IgG and fecal IgA levels by day 36 that cross-reacted with native SEB. Surprisingly, the inclusion of cholera toxin adjuvant in vaccine formulations containing rmSEB did not result in increased antibody responses compared to formulations using the immunogen alone. Taken together, these studies provide additional evidence for the potential use of nontoxic forms of SEB as vaccines.