Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity
Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity
复制标题
DOI：
10.4049/jimmunol.172.10.6290
复制
发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Goudsmit, J
中科院分区：
文献类型：
--
作者：
Barouch, DH;Pau, MG;Goudsmit, J
人类对5型腺病毒(Ad5)原有免疫的高流行率可能会大大限制基于Ad5载体的重组疫苗对HIV-1和其他病原体的免疫原性和临床应用。这个问题的一个潜在解决方案是使用腺病毒(Ad)血清型衍生的疫苗载体，这些血清型在人类中很少见，例如Ad35。然而，异种Ad血清型之间的交叉反应免疫反应已被描述，并可能被证明是这一策略的主要限制。特别是，Ad5和Ad35之间的免疫交叉反应程度以前还没有确定。在这项研究中，我们研究了预先存在的抗Ad5免疫对表达SIV Gag的rAd5和rAd35候选疫苗在小鼠体内的免疫原性的影响。在人类中常见的抗Ad5免疫水平极大地削弱了rAd5-Gag的免疫原性。相反，即使高水平的抗Ad5免疫也不能实质上抑制rAd35-Gag诱导的Gag特异性细胞免疫反应。观察到低水平的交叉反应Ad5/Ad35特异性的CD4(+)T淋巴细胞反应，但不足以抑制疫苗的免疫原性。这些数据表明，Ad35作为一种被抗Ad5免疫抑制最小的候选疫苗载体的潜在用途。此外，这些研究表明，使用来自免疫不同血清型的Ad载体可能是克服预先存在的抗Ad免疫的抑制效应的有效和普遍的策略。
The high prevalence of pre-existing immunity to adenovirus serotype 5 (Ad5) in human populations may substantially limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for HIV-1 and other pathogens. A potential solution to this problem is to use vaccine vectors derived from adenovirus (Ad) serotypes that are rare in humans, such as Ad35. However, cross-reactive immune responses between heterologous Ad serotypes have been described and could prove a major limitation of this strategy. In particular, the extent of immunologic cross-reactivity between Ad5 and Ad35 has not previously been determined. In this study we investigate the impact of pre-existing anti-Ad5 immunity on the immunogenicity of candidate rAd5 and rAd35 vaccines expressing SIV Gag in mice. Anti-Ad5 immunity at levels typically found in humans dramatically blunted the immunogenicity of rAd5-Gag. In contrast, even high levels of anti-Ad5 immunity did not substantially suppress Gag-specific cellular immune responses elicited by rAd35-Gag. Low levels of cross-reactive Ad5/Ad35-specific CD4(+) T lymphocyte responses were observed, but were insufficient to suppress vaccine immunogenicity. These data demonstrate the potential utility of Ad35 as a candidate vaccine vector that is minimally suppressed by anti-Ad5 immunity. Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity.