A cocktail of Mycobacterium bovis BCG recombinants expressing the SIV Nef, Env, and Gag antigens induces antibody and cytotoxic responses in mice vaccinated by different mucosal routes

A cocktail of Mycobacterium bovis BCG recombinants expressing the SIV Nef, Env, and Gag antigens induces antibody and cytotoxic responses in mice vaccinated by different mucosal routes
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DOI:
10.1089/aid.1998.14.1625
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发表时间:
1998-12-20
影响因子:
1.5
通讯作者:
Gheorghiu, M
Gheorghiu, M
中科院分区:
医学4区
文献类型:
--
作者:
Lagranderie, M;Winter, N;Gheorghiu, M

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表达不同人类免疫缺陷病毒(HIV)或猴免疫缺陷病毒(SIV)抗原的重组活牛分枝杆菌BCG株(rBCG)可能是开发抗艾滋病疫苗的良好候选者。为了开发有效的HIV/SIV疫苗,针对多种抗原的体液和细胞免疫应答对于控制感染可能是必不可少的。在这项研究中,我们免疫BALB/c小鼠通过不同的粘膜途径(口服,产气,鼻,直肠)与三个rBCG菌株的混合物表达,分别是整个SIVmac 251 Nef蛋白,和大片段的Env和Gag蛋白。研究的所有免疫途径诱导免疫球蛋白A(伊加)抗体对结核分枝杆菌PPD,SIV Env,SIV Gag抗原在粪便和支气管灌洗液以及特异性免疫球蛋白G(IgG)在血清中。无论粘膜免疫途径如何,均观察到脾细胞对Nef、Env和Gag的强特异性细胞毒性反应。因此,用rBCG菌株的混合物进行粘膜接种诱导针对所表达的三种SIV抗原的局部特异性伊加、系统性IgG和系统性CTL。直肠和口服途径似乎是用于预防SIV感染的最合适的接种途径。
Recombinant live Mycobacterium bovis BCG strains (rBCG) expressing different human immunodeficiency virus (HIV) or simian immunodeficiency (SIV) antigens could be good candidates for the development of vaccines against AIDS. To develop effective HIV/SIV vaccines, humoral and cellular immune responses directed against multiple antigens may be essential for the control of the infection. In this study we immunized BALB/c mice via different mucosal routes (oral, aerogenic, nasal, and rectal) with a mixture of three rBCG strains expressing, respectively, the entire SIVmac251 Nef protein, and large fragments of the Env and Gag proteins. All routes of immunization studied induced immunoglobulin A (IgA) antibodies against mycobacterial PPD, SIV Env, and SIV Gag antigens in feces and bronchial lavages as well as specific immunoglobulin G (IgG) in serum. Strong, specific cytotoxic responses of splenocytes against Nef, Env, and Gag was observed whatever the mucosal route of immunization. Therefore, mucosal vaccination with a cocktail of rBCG strains induces local, specific IgA, systemic IgG, and systemic CTLs against the three SIV antigens expressed. Rectal and oral routes seemed the most appropriate route of vaccination to be used to protect against SIV infection.