Hu S L, Klaniecki J, Dykers T, Sridhar P, Travis B M
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA.
AIDS Res Hum Retroviruses. 1991 Jul;7(7):615-20. doi: 10.1089/aid.1991.7.615.
Anti-human immunodeficiency virus type 1 (Anti-HIV-1) antibody response was compared in four groups of mice following inoculation with HIV-1 gp160, with live recombinant vaccinia virus expressing HIV-1 envelope glycoproteins, or with both immunogens in alternate orders for primary or secondary immunizations. Both subunit and recombinant virus immunogens induced similar levels of antibody response following primary immunization. However, after secondary immunization, mice primed with live recombinant virus and then boosted with subunit gp160 immunogen showed significantly higher antibody response than those in the other three groups. Neutralizing antibodies were generated only in this group of mice and were shown to neutralize both the homologous virus (BRU) and a divergent isolate (SF2) of HIV-1. On the other hand, their reactivities to peptide sequences from the principal neutralizing determinant (PND) of gp120 were limited to the BRU isolate, not SF2 or MN, indicating that the cross-neutralizing activities were directed against determinants other than the linear epitope(s) within the PND. These results also indicate that combined immunization by priming with liver recombinant virus and boosting with subunit immunogen may be more effective than immunization by either immunogen alone.
在四组小鼠接种HIV-1 gp160、表达HIV-1包膜糖蛋白的活重组痘苗病毒或在初次或二次免疫中以交替顺序使用这两种免疫原后,比较了它们的抗人类免疫缺陷病毒1型(抗HIV-1)抗体反应。初次免疫后,亚单位和重组病毒免疫原诱导的抗体反应水平相似。然而,二次免疫后,先用活重组病毒免疫然后用亚单位gp160免疫原加强免疫的小鼠,其抗体反应明显高于其他三组。仅在这组小鼠中产生了中和抗体,并且显示这些中和抗体能中和HIV-1的同源病毒(BRU)和一种不同的分离株(SF2)。另一方面,它们对来自gp120主要中和决定簇(PND)的肽序列的反应性仅限于BRU分离株,而不是SF2或MN,这表明交叉中和活性针对的是PND内线性表位以外的决定簇。这些结果还表明,先用活重组病毒免疫然后用亚单位免疫原加强免疫的联合免疫可能比单独使用任何一种免疫原进行免疫更有效。