Esquivel-Pérez Rita, Moreno-Fierros Leticia
Laboratorio de Inmunidad en Mucosas, Unidad de Biomedicina, FES-Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla, México.
Viral Immunol. 2005;18(4):695-708. doi: 10.1089/vim.2005.18.695.
Evidence from several sources support the assertion that cholera toxin (CT) is a potent immunogen and mucosal adjuvant; however there are also reports showing its lack of adjuvanticity against some antigens. Cry1Ac protoxin also exerts adjuvant effects in the antibody responses to proteins and polysaccharides but its adjuvanticity with regard to peptide vaccines had not been tested. To probe whether the adjuvant effects of these proteins varied depending on the antigen co-administered, we evaluated antipeptide antibody responses in serum and mucosal samples (vaginal, intestinal, and pulmonary) of mice that were immunized by intranasal or intraperitoneal routes with one of two distinct hybrid C4/V3 HIV peptides, either alone or with CT or Cry1Ac. The tested HIV 1 peptides differed in two aminoacids, T1SP10MN(A) was modified at the SP10 region by the substitution of the isoleucines 12 and 14 for cysteines and was called modified (m)T1SP10MN(A). Our data indicate that the adjuvant effects of CT and Cry1Ac are different. In addition they vary depending on the antigen co-administered and the number of antigen doses, because after three doses moderate adjuvant effects of CT and Cry1Ac on anti-peptide serum and mucosal antibody responses were observed only against the mT1SP10MN(A). In contrast, to attain significant adjuvant effects against the T1SP10MN, four doses were required. Interestingly we found that modification of the HIV peptide increases its immunogenicity without altering the principal neutralizing determinant (SP10).
来自多个来源的证据支持霍乱毒素（CT）是一种有效的免疫原和黏膜佐剂这一说法；然而，也有报告显示其对某些抗原缺乏佐剂活性。Cry1Ac原毒素在对蛋白质和多糖的抗体反应中也发挥佐剂作用，但尚未测试其对肽疫苗的佐剂活性。为了探究这些蛋白质的佐剂作用是否因共同给药的抗原而异，我们评估了通过鼻内或腹腔途径用两种不同的杂交C4/V3 HIV肽之一单独或与CT或Cry1Ac免疫的小鼠血清和黏膜样本（阴道、肠道和肺部）中的抗肽抗体反应。所测试的HIV-1肽在两个氨基酸上有所不同，T1SP10MN(A)在SP10区域通过将异亮氨酸12和14替换为半胱氨酸进行了修饰，被称为修饰的（m）T1SP10MN(A)。我们的数据表明，CT和Cry1Ac的佐剂作用不同。此外，它们因共同给药的抗原和抗原剂量的数量而异，因为在三剂后，仅在针对mT1SP10MN(A)时观察到CT和Cry1Ac对抗肽血清和黏膜抗体反应有中等程度的佐剂作用。相比之下，为了对T1SP10MN获得显著的佐剂作用，则需要四剂。有趣的是，我们发现HIV肽的修饰增加了其免疫原性，而不改变主要中和决定簇（SP10）。
