Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology Program, Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
PLoS One. 2013 Jul 3;8(7):e67574. doi: 10.1371/journal.pone.0067574. Print 2013.
Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m.) or intravaginal (ivag.) routes with helper-dependent adenoviral (HD-Ad) vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5) prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm) responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination.
大多数 HIV-1 感染被认为发生在性接触过程中的粘膜表面。有人假设，在粘膜表面递送的疫苗可能比系统递送的疫苗更能有效地预防 HIV-1。为了验证这一点，恒河猴通过肌肉内（i.m.）或阴道内（ivag.）途径接种了表达 HIV-1 包膜的辅助依赖性腺病毒（HD-Ad）载体。在使用表达 env 的同种 C HD-Ad6、Ad1、Ad5 和 Ad2 进行血清型转换之前，先通过鼻腔免疫接种 C 型腺病毒血清型 5（Ad5），然后对恒河猴进行直肠挑战，用 CCR5 嗜性 SHIV-SF162P3 进行攻击。通过系统途径接种会在 PBMC 中产生更强的全身 CD8 T 细胞反应，但粘膜反应较弱。相反，粘膜免疫会在结肠中产生更强的 CD4 T 细胞中央记忆（Tcm）反应。肌肉内免疫会产生更高水平的 env 结合抗体，但两者都不能产生中和或细胞毒性抗体。在粘膜 SHIV 攻击后，两组动物都比对照组动物更好地控制了 SHIV。然而，在阴道内组中，更多的动物的病毒设定点比肌肉内组低。这些数据表明，粘膜接种可能改善对性传播 HIV 的保护。这些数据还表明，辅助依赖性腺病毒疫苗可以在对 Ad5 有预先免疫和在四次腺病毒接种期间介导强大的疫苗反应。
