Liniger Matthias, Zuniga Armando, Morin Teldja Neige Azzouz, Combardiere Behazine, Marty Rene, Wiegand Marian, Ilter Orhan, Knuchel Marlyse, Naim Hussein Y
Crucell - Berna Biotech LTD, Rehhagstrasse 79, 3018 Bern, Switzerland.
Vaccine. 2009 May 26;27(25-26):3299-305. doi: 10.1016/j.vaccine.2009.01.057. Epub 2009 Feb 5.
Recombinant measles viruses (rMV) based on the live attenuated measles vaccine strain (MVb) expressing antigens of HIV-1 clade B were generated by reverse genetics. Recombinants expressing single or double antigens of HIV-1 (rMV-HIV) were genetically highly stable on human diploid cells. The production process of these viruses was essentially similar to the parental MV strain, yielding comparative end titers. Immunization of tg-mice by different regimens and formulations showed potent humoral and cellular immune responses against MV and HIV antigens. Recombinant MV-HIV expressing Gag protein conferred protective immunity in tg-mice after a high-dose pseudochallenge with recombinant vaccinia virus. In addition, rMV-HIV boosted anti-HIV antibodies, in the presence of pre-existing anti-vector antibodies.
基于表达HIV-1 B亚型抗原的减毒活麻疹疫苗株(MVb),通过反向遗传学技术构建了重组麻疹病毒(rMV)。表达HIV-1单抗原或双抗原的重组体(rMV-HIV)在人二倍体细胞上具有高度的遗传稳定性。这些病毒的生产过程与亲本MV株基本相似,最终滴度相当。采用不同免疫方案和剂型对转基因小鼠进行免疫,可诱导出针对MV和HIV抗原的强效体液免疫和细胞免疫反应。在用重组痘苗病毒进行高剂量假攻击后,表达Gag蛋白的重组MV-HIV在转基因小鼠中提供了保护性免疫。此外,在预先存在抗载体抗体的情况下,rMV-HIV可增强抗HIV抗体。