Carozza Marlène, Rodrigues Valérie, Unterfinger Yves, Galea Sandra, Coulpier Muriel, Klonjkowski Bernard, Thiaucourt François, Totté Philippe, Richardson Jennifer
Centre International de Recherche en Agronomie pour le Développement, UMR CMAEE, Montpellier, France; INRA, UMR 1309 CMAEE, Montpellier, France; INRA, UMR 1161 Virologie, 7 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; ANSES, UMR Virologie, 23 avenue du Général de Gaulle, 94700 Maisons-Alfort, France; Université Paris-Est, Ecole Nationale Vétérinaire d'Alfort, UMR Virologie, Maisons-Alfort F-94704, France.
Centre International de Recherche en Agronomie pour le Développement, UMR CMAEE, Montpellier, France; INRA, UMR 1309 CMAEE, Montpellier, France.
Vaccine. 2015 Jan 1;33(1):141-8. doi: 10.1016/j.vaccine.2014.10.088. Epub 2014 Nov 11.
Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides small colony type (MmmSC), is a devastating respiratory disease of cattle. In sub-Saharan Africa, where CBPP is enzootic, live attenuated vaccines are deployed but afford only short-lived protection. In cattle, recovery from experimental MmmSC infection has been associated with the presence of CD4(+) T lymphocytes that secrete interferon gamma in response to MmmSC, and in particular to the lipoprotein A (LppA) antigen. In an effort to develop a better vaccine against CBPP, a viral vector (Ad5-LppA) that expressed LppA was generated from human adenovirus type 5. The LppA-specific immune responses elicited by the Ad5-LppA vector were evaluated in mice, and compared to those elicited by recombinant LppA formulated with a potent adjuvant. Notably, a single administration of Ad5-LppA, but not recombinant protein, sufficed to elicit a robust LppA-specific humoral response. After a booster administration, both vector and recombinant protein elicited strong LppA-specific humoral and cell-mediated responses. Ex vivo stimulation of splenocytes induced extensive proliferation of CD4(+) T cells for mice immunized with vector or protein, and secretion of T helper 1-associated and proinflammatory cytokines for mice immunized with Ad5-LppA. Our study - by demonstrating the potential of a viral-vectored prototypic vaccine to elicit prompt and robust immune responses against a major antigen of MmmSC - represents a first step in developing a recombinant vaccine against CBPP.
牛传染性胸膜肺炎(CBPP)由丝状支原体丝状亚种小菌落型(MmmSC)引起,是一种严重的牛呼吸道疾病。在撒哈拉以南非洲地区,CBPP呈地方流行,使用的是减毒活疫苗,但仅能提供短期保护。在牛身上,从实验性MmmSC感染中恢复与分泌γ干扰素以响应MmmSC,特别是脂蛋白A(LppA)抗原的CD4(+) T淋巴细胞的存在有关。为了研发一种更好的抗CBPP疫苗,利用人5型腺病毒构建了表达LppA的病毒载体(Ad5-LppA)。评估了Ad5-LppA载体引发的LppA特异性免疫反应,并与用强效佐剂配制的重组LppA引发的反应进行了比较。值得注意的是,单次给予Ad5-LppA即可引发强烈的LppA特异性体液反应,而重组蛋白则不能。加强免疫后,载体和重组蛋白均引发了强烈的LppA特异性体液和细胞介导反应。对脾细胞进行体外刺激,发现用载体或蛋白免疫的小鼠的CD4(+) T细胞大量增殖,而用Ad5-LppA免疫的小鼠分泌了与辅助性T细胞1相关的促炎细胞因子。我们的研究——通过证明病毒载体原型疫苗针对MmmSC主要抗原引发快速而强烈免疫反应的潜力——是研发抗CBPP重组疫苗的第一步。