Ellenberger Dennis L, Li Bin, Lupo L Davis, Owen S Michele, Nkengasong John, Kadio-Morokro Madeleine Sassan, Smith James, Robinson Harriet, Ackers Marta, Greenberg Alan, Folks Thomas, Butera Salvatore
HIV and Retrovirology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Virology. 2002 Oct 10;302(1):155-63. doi: 10.1006/viro.2002.1577.
We considered several key issues regarding the development of a DNA-based human immunodeficiency virus type 1 (HIV-1) vaccine: (1) should the candidate vaccine construct be derived from incident or prevalent HIV-1 strains; and (2) should circulating plasma virus, archived HIV-1 provirus recovered from peripheral blood mononuclear cells, or both be included? To address these questions, we collected circulating HIV-1 strains from infected individuals residing in Abidjan, Côte d'Ivoire. From a panel of 23 strains, 22 were HIV-1 subtype A in gag, 19 of which phylogenetically clustered with the recombinant HIV-1, CRF02-AG strains from West Africa. The mosaic genome of CRF02-AG was confirmed by sequencing the protease gene. A consensus gag p24 protein sequence was generated and 147 of 148 codons were identical to CRF02-AG (IbNG). Regardless of the sequence origin (RNA, provirus, incident, or prevalent), the gag p24 consensus sequences were highly representative of these distinct virologic compartments. These data suggest that the consensus sequence generated from incident and prevalent infections may provide an appropriate sequence for a DNA vaccine and is largely representative of the major circulating viral strain.
我们考虑了关于开发基于DNA的1型人类免疫缺陷病毒(HIV-1)疫苗的几个关键问题:(1)候选疫苗构建体应来源于新发还是流行的HIV-1毒株;以及(2)是否应纳入循环血浆病毒、从外周血单核细胞中回收的存档HIV-1前病毒,或两者都纳入?为了解决这些问题,我们从居住在科特迪瓦阿比让的受感染个体中收集了循环HIV-1毒株。在一组23株毒株中,22株在gag基因中为HIV-1 A亚型,其中19株在系统发育上与来自西非的重组HIV-1 CRF02-AG毒株聚类。通过对蛋白酶基因进行测序证实了CRF02-AG的镶嵌基因组。生成了一个共有gag p24蛋白序列,148个密码子中的147个与CRF02-AG(IbNG)相同。无论序列来源(RNA、前病毒、新发或流行)如何,gag p24共有序列都高度代表了这些不同的病毒学区室。这些数据表明,从新发和流行感染中产生的共有序列可能为DNA疫苗提供合适的序列,并且在很大程度上代表了主要的循环病毒株。