Rasmussen Robert A, Ong Helena, Song Ruijiang, Chenine Agnès-Laurence, Ayash-Rashkovsky Mila, Hu Shiu-Lok, Polacino Patricia, Else James G, Novembre Francis J, Ruprecht Ruth M
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
AIDS. 2007 Sep 12;21(14):1841-8. doi: 10.1097/QAD.0b013e32828684ea.
To determine whether multigenic protein immunogens including native, trimeric HIV clade C (HIV-C) gp160 could cross-protect macaques against mucosal challenge with clade C (SHIV-C) mismatched for env.
Because AIDS vaccine recipients are unlikely to encounter exactly matched HIV strains and to represent the diversity of locally circulating HIV-C strains, we selected env genes to generate the gp160 immunogen and SHIV-C from different, recently infected infants of the same clinical cohort in Zambia. In a model of postnatal HIV-C transmission, infant macaques were immunized with soluble viral proteins, including trimeric HIV1084i Env, and challenged with SHIV-1157ip; protein-only vaccination was compared with a DNA prime/protein boost strategy.
All vaccinated and control monkeys were exposed orally to low-dose, R5-tropic SHIV-1157ip encoding heterologous env. Animals with no or only transient infection were rechallenged intrarectally with a high dose of R5 SHIV-1157ipd3N4, a 'late', animal-evolved SHIV-1157ip variant. Animals were followed prospectively for immune parameters and viral RNA loads.
Vaccination induced cross-neutralizing antibodies. Compared to controls, vaccinees had significantly lower peak viral RNA loads, and one vaccine recipient remained completely virus-free, even in lymphoid tissues. There was a trend for the protein-only vaccine to yield better protection than the combined modality approach.
Protein-only immunogens induced significant protection against heterologous viruses encoding env from locally circulating viruses.
确定包括天然三聚体HIV C亚型（HIV-C）gp160在内的多基因蛋白免疫原是否能交叉保护猕猴免受env基因不匹配的C亚型猿猴-人免疫缺陷病毒（SHIV-C）的黏膜攻击。
由于艾滋病疫苗接种者不太可能遇到完全匹配的HIV毒株，且为了代表当地流行的HIV-C毒株的多样性，我们从赞比亚同一临床队列中近期感染的不同婴儿中选择env基因来生成gp160免疫原和SHIV-C。在产后HIV-C传播模型中，用可溶性病毒蛋白（包括三聚体HIV1084i Env）对幼猴进行免疫，并使其感染SHIV-1157ip；将单纯蛋白疫苗接种与DNA初免/蛋白加强策略进行比较。
所有接种疫苗和对照的猴子经口暴露于低剂量、R5嗜性的编码异源env的SHIV-1157ip。对未感染或仅短暂感染的动物经直肠再次用高剂量的R5 SHIV-1157ipd3N4（一种后期的、动物进化的SHIV-1157ip变体）进行攻击。对动物进行前瞻性跟踪，观察免疫参数和病毒RNA载量。
疫苗接种诱导了交叉中和抗体。与对照组相比，疫苗接种者的病毒RNA载量峰值显著较低，一名疫苗接种者即使在淋巴组织中也完全没有病毒。单纯蛋白疫苗比联合免疫方法有产生更好保护作用的趋势。
单纯蛋白免疫原对编码来自当地流行病毒的env的异源病毒诱导了显著的保护作用。
