Santra Sampa, Sun Yue, Korioth-Schmitz Birgit, Fitzgerald Julie, Charbonneau Cherie, Santos Giannina, Seaman Michael S, Ratcliffe Sarah J, Montefiori David C, Nabel Gary J, Ertl Hildegund C J, Letvin Norman L
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Vaccine. 2009 Sep 25;27(42):5837-45. doi: 10.1016/j.vaccine.2009.07.050. Epub 2009 Aug 4.
Pre-existing immunity to human adenovirus serotype 5 (AdHu5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAdHu5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. As a potential solution to this problem we developed adenovirus vaccine vectors of chimpanzee origin. In the present study we assessed the immunogenicity of various chimpanzee adenovirus vectors in a prime/boost regimen to HIV-1 envelope and SIV Gag-Pol in rhesus monkeys and their ability to protect against pathogenic viral challenge. Although rAdHu5-primed monkeys had higher magnitude T cell responses than rAdC7 or rAdC68 prior to challenge, the rAdC7-rAdC1/C5 and rAdHu5-rAdC1/C5 immunizations resulted in comparable magnitude recall cellular immune responses and comparable level of control of viremia post-challenge.
在临床前研究和临床试验中均已表明，对人腺病毒5型（AdHu5）的既有免疫力会抑制基于重组Ad5（rAdHu5）载体的人类免疫缺陷病毒1型（HIV-1）疫苗的免疫原性。作为解决该问题的一种潜在方法，我们开发了源自黑猩猩的腺病毒疫苗载体。在本研究中，我们评估了多种黑猩猩腺病毒载体在恒河猴中针对HIV-1包膜和SIV Gag-Pol的初免/加强免疫方案中的免疫原性，以及它们预防致病性病毒攻击的能力。尽管在攻击前，用rAdHu5初免的猴子比用rAdC7或rAdC68初免的猴子具有更高强度的T细胞反应，但rAdC7-rAdC1/C5和rAdHu5-rAdC1/C5免疫接种产生了相当强度的回忆性细胞免疫反应以及攻击后相当水平的病毒血症控制。
