Acosta-Rivero Nelson, Poutou Joanna, Alvarez-Lajonchere Liz, Guerra Ivis, Aguilera Yaraima, Musacchio Alexis, Rodríguez Armando, Aguilar Julio C, Falcon Viviana, Alvarez-Obregon Julio C, Soria Yordanka, Torres Dinorah, Linares Marbelis, Pérez Angel, Morales-Grillo Juan, Dueñas-Carrera Santiago
Center for Genetic Engineering and Biotechnology, Havana City, Cuba.
Biol Res. 2009;42(1):41-56. Epub 2009 Jun 11.
In the present work, immunogenicity of recombinant in vitro assembled hepatitis C virus core particles, HCcAg.120-VLPs, either alone or in combination with different adjuvants was evaluated in BALB/c mice. HCcAg.120-VLPs induced high titers of anti-HCcAg.120 antibodies and virus-specific cellular immune responses. Particularly, HCcAg.120-VLPs induced specific delayed type hypersensitivity, and generated a predominant T helper 1 cytokine pro file in immunized mice. In addition, HCcAg.120-VLPs prime splenocytes proliferate in vitro against different HCcAg.120-specific peptides, depending on either the immunization route or the adjuvant used. Remarkably, immunization with HCcAg.120-VLPs/Montanide ISA888 formulation resulted in a significant control of vaccinia virus titer in mice after challenge with a recombinant vaccinia virus expressing HCV core protein, vvCore. Animals immunized with this formulation had a marked increase in the number of IFN-gamma producing spleen cells, after stimulation with P815 cells infected with vvCore. These results suggest the use of recombinant HCV core particles as components of therapeutic or preventive vaccine candidates against HCV.
在本研究中,我们在BALB/c小鼠中评估了重组体外组装的丙型肝炎病毒核心颗粒HCcAg.120-VLPs单独或与不同佐剂联合使用时的免疫原性。HCcAg.120-VLPs诱导产生了高滴度的抗HCcAg.120抗体和病毒特异性细胞免疫反应。特别是,HCcAg.120-VLPs诱导了特异性迟发型超敏反应,并在免疫小鼠中产生了主要的辅助性T细胞1细胞因子谱。此外,根据免疫途径或所用佐剂的不同,HCcAg.120-VLPs致敏的脾细胞在体外对不同的HCcAg.120特异性肽发生增殖反应。值得注意的是,用HCcAg.120-VLPs/蒙旦蜡ISA888制剂免疫的小鼠在受到表达HCV核心蛋白的重组痘苗病毒vvCore攻击后,其痘苗病毒滴度得到了显著控制。用该制剂免疫的动物在用vvCore感染的P815细胞刺激后,产生IFN-γ的脾细胞数量显著增加。这些结果表明,重组HCV核心颗粒可作为抗HCV治疗性或预防性候选疫苗的成分。