Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge.
Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge.
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作者：
粘液组织是大多数呼吸道和性传播疾病，包括人类免疫缺陷病毒的主要传播途径。我们的目的是通过将重组腺病毒血清型5（rAd 5）靶向肺，在恒河猴中产生对猴免疫缺陷病毒（SIV）的强粘膜免疫应答。在静脉内（IV）或直肠内（IR）SIVmac 251攻击模型中，将气雾剂（AE）疫苗接种的免疫原性和效力与肌内（IM）递送进行比较。雾化的rAd 5诱导强的细胞反应，在肺和全身体液反应相当于IM。引人注目的是，所有免疫组在IV攻击模型中将急性病毒血症控制了1 - 2个对数。相比之下，IR攻击后，只有峰值病毒血症减少免疫接种，SIV感染率或粘膜CD 4 + T细胞保存没有显着影响。改善的疾病结果与攻击前的细胞和体液应答相关，而攻击后的T细胞应答与病毒血症控制高度相关。通过全身和气道粘膜免疫实现的类似结果支持AE递送作为胃肠外疫苗接种的安全、有效和侵入性较小的替代方案。
Mucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus. We aimed to generate strong mucosal immune responses to simian immunodeficiency virus (SIV) in rhesus macaques by targeting recombinant adenovirus serotype 5 (rAd5) to the lung. The immunogenicity and efficacy of aerosol (AE) vaccination was compared with intramuscular (IM) delivery in either an intravenous (IV) or intrarectal (IR) SIVmac251 challenge model. Aerosolized rAd5 induced strong cellular responses in the lung and systemic humoral responses equivalent to IM. Strikingly, all immunization groups controlled acute viremia in the IV challenge model by 1 −2 logs. By contrast, after IR challenge, only peak viremia was reduced by immunization, with no significant effect on SIV infection acquisition rate or mucosal CD4+ T-cell preservation. Improved disease outcome was associated with pre-challenge cellular and humoral responses, while post-challenge T-cell responses were highly correlated with viremia control. The similar outcomes achieved by systemic and airway mucosal immunization support AE delivery as a safe, effective, and less invasive alternative to parenteral vaccination.
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影响因子：
20.3
作者：
Harari, A;Petitpierre, S;Pantaleo, G
通讯作者：
Pantaleo, G
影响因子：
2.2
作者：
Maecker, HT;Dunn, HS;Picker, LJ
通讯作者：
Picker, LJ
影响因子：
1.7
作者：
Cutts, FT;Clements, CJ;Bennett, JV
通讯作者：
Bennett, JV
影响因子：
5.4
作者：
Loffredo, John T.;Maxwell, Jess;Watkins, David I.
通讯作者：
Watkins, David I.
影响因子：
5.4
作者：
Crotty, S;Miller, CJ;Andino, R
通讯作者：
Andino, R