Beignon Anne-Sophie, Brown Fred, Eftekhari Pierre, Kramer Ed, Briand Jean-Paul, Muller Sylviane, Partidos Charalambos D
UPR 9021, Institut de Biologie Moléculaire et Cellulaire, CNRS, 15 rue René Descartes, F-67084 Strasbourg, France.
Vet Immunol Immunopathol. 2005 Apr 8;104(3-4):273-80. doi: 10.1016/j.vetimm.2004.12.008.
In this study a synthetic peptide representing residues 141-159 from the GH loop of VP1 protein of foot-and-mouth disease virus was tested for its capacity to elicit virus neutralising antibodies in mice after transcutaneous immunisation. Topical application of the peptide conjugated to bovine serum albumin together with cholera toxin as an adjuvant elicited anti-peptide antibody responses with strong virus neutralising activity. The combination of cholera toxin with an immunostimulatory CpG motif resulted in the induction of IgG1 and IgG2a anti-peptide antibodies with significantly enhanced virus neutralising activity. To shed more light on the mechanisms of cholera toxin adjuvanticity we demonstrated its binding to keratinocytes via GM(1)-gangliosides. This was followed by an increase of the intracellular cAMP and the rapid diffusion of cholera toxin throughout the epidermis. These findings demonstrate that peptide-based vaccines when combined with the appropriate adjuvant(s) can elicit potent virus neutralising antibody responses after transcutaneous immunisation. However, experiments in target species will be required to confirm the potential of this simple vaccination procedure in livestock.
在本研究中,对口蹄疫病毒VP1蛋白GH环中141 - 159位残基的合成肽进行了测试,以评估其经皮免疫后在小鼠体内引发病毒中和抗体的能力。将与牛血清白蛋白偶联的该肽与霍乱毒素作为佐剂进行局部应用,引发了具有强大病毒中和活性的抗肽抗体反应。霍乱毒素与免疫刺激CpG基序的组合导致诱导出具有显著增强的病毒中和活性的IgG1和IgG2a抗肽抗体。为了更深入了解霍乱毒素佐剂作用的机制,我们证明了它通过GM(1)-神经节苷脂与角质形成细胞结合。随后细胞内cAMP增加,霍乱毒素在整个表皮迅速扩散。这些发现表明,基于肽的疫苗与适当的佐剂联合使用时,经皮免疫后可引发有效的病毒中和抗体反应。然而,需要在目标物种中进行实验,以确认这种简单疫苗接种程序在牲畜中的潜力。