School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
J Acquir Immune Defic Syndr. 2011 Apr 15;56(5):384-92. doi: 10.1097/QAI.0b013e31820a4a8d.
The development of a safe, effective, and affordable microbicide to prevent the sexual transmission of HIV combination is urgently needed. Our previous studies demonstrated that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) exhibited potent antiviral activity against a broad spectrum of HIV, simian immunodeficiency virus, and herpes simplex virus, making it a promising candidate as a component of combination microbicide. We intended to evaluate potential the synergistic anti-HIV-1 effect of HP-OVA in combination with antiretroviral drug (ARV)-based microbicide candidates.
The antiviral activity of HP-OVA and the ARVs, including HIV-1 entry inhibitors (T20, C52L, NB64, NBD556, AMD3100, and Maraviroc) and reverse transcriptase inhibitors (Tenofovir, UC781, and TMC120), tested alone or in combination, against HIV-1 X4 and R5 viruses, including some drug-resistant strains, was determined in MT-2 and peripheral blood mononuclear cells using p24 assay. The immune responses induced by HP-OVA that was applied in the vaginas of rats were detected by enzyme-linked immunosorbent assay.
When each of these ARV-based microbicide candidates was combined with HP-OVA, synergistic activity was observed against infection by both X4 and R5 strains, and the degree of synergy differed in each case. HP-OVA was highly effective against several ARV-resistant HIV-1 strains, suggesting that combining HP-OVA with these ARV-based microbicide candidates might work cooperatively against both drug-sensitive and -resistant HIV-1 strains. Human body fluids and human proteins had little or no effects on HP-OVA-mediated inhibitory activity against HIV-1 infection. HP-OVA formulated in the universal gel maintained its antiviral activity for at least 1 month and only induced weak immune responses after its multiple applications in the vaginas of rats.
Synergistic and complementary effects against infection by a broad spectrum of HIV-1 strains were observed by combining HP-OVA with the ARV-based microbicide candidates. These findings provide a sound scientific platform for the development of a safe, effective, and affordable combination microbicide to prevent the sexual transmission of HIV and other sexually transmissible viruses.
急需开发一种安全、有效且负担得起的杀微生物剂来预防 HIV 病毒的性传播。我们之前的研究表明，3-羟基邻苯二甲酸酐修饰的鸡卵清白蛋白（HP-OVA）对广谱的 HIV、猴免疫缺陷病毒和单纯疱疹病毒均具有强大的抗病毒活性，使其成为组合杀微生物剂的有前途的候选物之一。我们旨在评估 HP-OVA 与基于抗逆转录病毒药物（ARV）的杀微生物候选物联合使用的潜在协同抗 HIV-1 效果。
使用 p24 测定法，在 MT-2 和外周血单核细胞中，分别检测 HP-OVA 与 HIV-1 进入抑制剂（T20、C52L、NB64、NBD556、AMD3100 和马拉维若）和逆转录酶抑制剂（替诺福韦、UC781 和 TMC120）单独或联合使用时对 X4 和 R5 病毒（包括一些耐药株）的抗病毒活性。通过酶联免疫吸附试验检测 HP-OVA 在大鼠阴道中应用所引起的免疫反应。
当将这些基于 ARV 的杀微生物候选物中的每一种与 HP-OVA 联合使用时，观察到对 X4 和 R5 株感染的协同作用，并且每种情况下的协同作用程度不同。HP-OVA 对几种 ARV 耐药的 HIV-1 株非常有效，表明将 HP-OVA 与这些基于 ARV 的杀微生物候选物联合使用可能对敏感和耐药的 HIV-1 株均具有协同作用。人体体液和人体蛋白对 HP-OVA 介导的抑制 HIV-1 感染的活性几乎没有或没有影响。在通用凝胶中配制的 HP-OVA 至少能保持 1 个月的抗病毒活性，并且在大鼠阴道中多次应用后仅引起微弱的免疫反应。
将 HP-OVA 与基于 ARV 的杀微生物候选物联合使用时，观察到对广谱 HIV-1 株感染的协同和互补作用。这些发现为开发安全、有效且负担得起的组合杀微生物剂以预防 HIV 和其他性传播病毒的性传播提供了可靠的科学平台。
