Antibody-like molecules were evaluated with potent simian immunodeficiency virus (SIV) neutralizing properties (immunoadhesins) that were delivered by a recombinant adeno-associated virus (rAAV) vector in the SIV-infected rhesus macaque model. When injected intramuscularly into the host, the vector directs in vivo production of the transgenes with antibody-like binding properties that lead to serum neutralizing activity against SIV. To extend the half-life of the immunoadhesins, rhesus cluster of differentiation 4 (CD4) and a single-chain antibody (4L6) were fused with albumin molecules, and these constructs were tested in our model of SIV infection. Antibody-based immunoadhesins provided high serum neutralizing titers against the original SIV strain. CD4-based immunoadhesins provided a wider spectrum of neutralization against different SIV strains in comparison to antibody-based therapeutics and had the potential to protect against high viral challenging doses. Although the albumin-antibody fusion immunoadhesin provided strong and prolonged protection of the immunized animals against SIV challenge, the albumin-CD4 fusion altered the specificity and decreased the overall protection effectiveness of the immunoadhesin in comparison to the antibody-based molecules. Albumin-based immunoadhesins increase in vivo longevity of the immune protection; however, they present challenges likely linked to the induction of anti-immunoadhesin antibodies.

使用重组腺相关病毒 (rAAV) 载体在感染 SIV 的恒河猴模型中传递的有效的猿猴免疫缺陷病毒 (SIV) 中和特性（免疫粘附素）来评估抗体样分子。当肌肉注射到宿主体内时，该载体指导体内产生具有抗体样结合特性的转基因，从而产生针对 SIV 的血清中和活性。为了延长免疫粘附素的半衰期，将恒河猴分化簇 4 (CD4) 和单链抗体 (4L6) 与白蛋白分子融合，并在我们的 SIV 感染模型中测试了这些构建体。基于抗体的免疫粘附素针对原始 SIV 毒株提供了高血清中和滴度。与基于抗体的疗法相比，基于 CD4 的免疫粘附素针对不同的 SIV 毒株提供了更广泛的中和作用，并且有可能抵御高病毒攻击剂量。尽管白蛋白-抗体融合免疫粘附素为免疫动物提供了针对SIV攻击的强而持久的保护，但与基于抗体的分子相比，白蛋白-CD4融合改变了免疫粘附素的特异性并降低了总体保护效果。基于白蛋白的免疫粘附素可增加体内免疫保护的寿命；然而，它们提出的挑战可能与抗免疫粘附素抗体的诱导有关。