Mattapallil Joseph J, Douek Daniel C, Buckler-White Alicia, Montefiori David, Letvin Norman L, Nabel Gary J, Roederer Mario
Vaccine Research Center, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
J Exp Med. 2006 Jun 12;203(6):1533-41. doi: 10.1084/jem.20060657. Epub 2006 May 30.
Acute simian immunodeficiency virus (SIV)/human immunodeficiency virus infection is accompanied by a massive destruction of CD4 memory T cells across all the tissue compartments. These early events set the course toward disease progression and immunodeficiency. Here, we demonstrate that prior vaccination reduces this destruction during acute SIV Mac251 infection, leading to better survival and long-term outcome. Systemic vaccination with a DNA-prime recombinant adenovirus boost regimen preserved memory CD4 T cells throughout the body. The vaccine regimen induced broad CD4 and CD8 T cell responses in all tissues examined and, importantly, induced antibodies that neutralized the primary isolate of SIV used for challenge. Finally, we demonstrate that the extent of preservation of the CD4 memory compartment during the acute phase provides a strong predictor for subsequent progression to death. Our data provide a mechanism to explain clinical observations that acute-phase viral loads predict long-term disease progression and underscore the need for interventions that protect against early destruction of CD4 memory T cells during acute infection.
急性猿猴免疫缺陷病毒（SIV）/人类免疫缺陷病毒感染伴随着所有组织区室中CD4记忆T细胞的大量破坏。这些早期事件为疾病进展和免疫缺陷奠定了基础。在此，我们证明预先接种疫苗可减少急性SIV Mac251感染期间的这种破坏，从而带来更好的生存率和长期预后。采用DNA初免重组腺病毒加强免疫方案进行全身接种可在全身保留记忆CD4 T细胞。该疫苗方案在所有检测组织中诱导了广泛的CD4和CD8 T细胞应答，重要的是，还诱导产生了中和用于攻击的SIV原始毒株的抗体。最后，我们证明急性期CD4记忆区室的保留程度可有力预测随后的死亡进展。我们的数据提供了一种机制来解释急性期病毒载量可预测长期疾病进展这一临床观察结果，并强调需要采取干预措施来防止急性感染期间CD4记忆T细胞的早期破坏。
