Unidade de Tecnologias de Proteínas e Anticorpos Monoclonais, Instituto de Higiene e Medicina Tropical, Estrada Paço Lumiar 22, Lisbon, Portugal.
J Virol. 2010 Dec;84(23):12429-36. doi: 10.1128/JVI.01102-10. Epub 2010 Sep 15.
Human immunodeficiency virus type 2 (HIV-2) infection affects about 1 to 2 million individuals, the majority living in West Africa, Europe, and India. As for HIV-1, new strategies for the prevention of HIV-2 infection are needed. Our aim was to produce new vaccine immunogens that elicit the production of broadly reactive HIV-2 neutralizing antibodies (NAbs). Native and truncated envelope proteins from the reference HIV-2ALI isolate were expressed in vaccinia virus or in bacteria. This source isolate was used due to its unique phenotype combining CD4 independence and CCR5 usage. NAbs were not elicited in BALB/c mice by single immunization with a truncated and fully glycosylated envelope gp125 (gp125t) or a recombinant polypeptide comprising the C2, V3, and C3 envelope regions (rpC2-C3). A strong and broad NAb response was, however, elicited in mice primed with gp125t expressed in vaccinia virus and boosted with rpC2-C3. Serum from these animals potently neutralized (median 50% neutralizing titer, 3,200) six of six highly divergent primary HIV-2 isolates. Coreceptor usage and the V3 sequence of NAb-sensitive isolates were similar to that of the vaccinating immunogen (HIV-2ALI). In contrast, NAbs were not reactive on three X4 isolates that displayed major changes in V3 loop sequence and structure. Collectively, our findings demonstrate that broadly reactive HIV-2 NAbs can be elicited by using a vaccinia virus vector-prime/rpC2-C3-boost immunization strategy and suggest a potential relationship between escape to neutralization and cell tropism.
人类免疫缺陷病毒 2 型（HIV-2）感染影响约 100 万至 200 万人，其中大多数生活在西非、欧洲和印度。与 HIV-1 一样，需要新的策略来预防 HIV-2 感染。我们的目标是产生新的疫苗免疫原，这些免疫原能够产生广泛反应的 HIV-2 中和抗体（NAb）。参考 HIV-2ALI 分离株的天然和截短包膜蛋白在痘苗病毒或细菌中表达。由于其独特的表型，即同时具有 CD4 非依赖性和 CCR5 使用性，因此使用了这种来源分离株。单独用截短和完全糖基化的包膜 gp125（gp125t）或包含 C2、V3 和 C3 包膜区的重组多肽（rpC2-C3）免疫 BALB/c 小鼠，不会引起 NAb。然而，用痘苗病毒表达的 gp125t 进行初次免疫，并用 rpC2-C3 进行加强免疫，可在小鼠中引发强烈和广泛的 NAb 反应。这些动物的血清可有效中和（中位数 50%中和滴度，3200）六种高度分化的原发性 HIV-2 分离株。NAb 敏感分离株的辅助受体使用和 V3 序列与接种免疫原（HIV-2ALI）相似。相比之下，对三种 X4 分离株的 NAb 没有反应，这些分离株的 V3 环序列和结构发生了重大变化。总的来说，我们的研究结果表明，使用痘苗病毒载体-初免/rpC2-C3-加强免疫策略可以引发广泛反应的 HIV-2 NAb，并提示中和逃逸与细胞嗜性之间可能存在关联。
