Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.
Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.
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DOI：
10.1371/journal.pone.0067574
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Barry MA
中科院分区：
文献类型：
--
作者：
Weaver EA;Nehete PN;Nehete BP;Yang G;Buchl SJ;Hanley PW;Palmer D;Montefiori DC;Ferrari G;Ng P;Sastry KJ;Barry MA
大多数HIV-1感染被认为是在性接触期间发生在粘膜表面。据推测，在黏膜表面注射的疫苗可能比系统注射的疫苗对HIV-1具有更好的保护作用。为了验证这一点，猕猴被肌肉注射疫苗(肌肉注射)。或阴道内(静脉注射)使用表达HIV-1包膜的辅助依赖腺病毒(HD-Ad)载体的路线。首先用CAd血清型5(Ad5)免疫猕猴，然后用表达env的CHD-Ad6、Ad1、Ad5和Ad2载体进行血清型转换，然后用CCR5嗜性Shiv-SF162P3直肠攻击。全身途径免疫后，PBMC产生较强的系统性CD8 T细胞反应，但较弱的粘膜反应。相反，粘膜免疫在结肠中产生了更强的CD4T细胞中央记忆(Tcm)反应。肌肉免疫产生更高水平的包膜结合抗体，但既不产生中和抗体，也不产生细胞毒抗体。在黏膜SIV攻击后，两组动物对SIV的控制均好于对照组。然而，更多的动物在瓶子里。组的病毒设定值低于IM组。一群人。这些数据表明，粘膜疫苗接种可能会改善对性传播艾滋病毒的保护。这些数据还表明，辅助者依赖的Ad疫苗可以在面对Ad5的先前免疫和在四轮腺病毒疫苗接种期间介导强大的疫苗应答。
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.
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影响因子：
5.4
作者：
McCoy, Kimberly;Tatsis, Nia;Ertl, Hildegund C. J.
通讯作者：
Ertl, Hildegund C. J.
影响因子：
5.4
作者：
Hsu, M;Harouse, JM;Cheng-Mayer, C
通讯作者：
Cheng-Mayer, C
影响因子：
82.9
作者：
Lubeck, MD;Natuk, R;RobertGuroff, M
通讯作者：
RobertGuroff, M
影响因子：
0.7
作者：
Hsu, M;Buckner, C;Chen-Mayer, C
通讯作者：
Chen-Mayer, C
影响因子：
4.4
作者：
Barouch, DH;Pau, MG;Goudsmit, J
通讯作者：
Goudsmit, J