Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-Ad5 immunity
Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-Ad5 immunity
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DOI：
10.1128/jvi.79.15.9694-9701.2005
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发表时间：
2005-08-01
影响因子：
5.4
通讯作者：
Barouch, DH
中科院分区：
文献类型：
--
作者：
Lemckert, AAC;Sumida, SM;Barouch, DH
人群中预先存在的腺病毒血清5型（Ad5）免疫的高流行率可能会限制重组Ad5 （rAd5）载体疫苗对人类免疫缺陷病毒I型和其他病原体的免疫原性和临床应用。这一问题的一个潜在解决方案是利用从罕见的Ad血清型（如Ad35和Ad11）衍生的rAd疫苗载体。我们之前报道过rAd35载体在存在抗ad5免疫的情况下具有免疫原性，但尚未充分探讨异种rAd初始-增强方案的免疫原性以及交叉反应性抗载体免疫可能限制这种方法的程度。本研究在具有和不具有抗ai15免疫的小鼠中评估了涉及rAd5、rAd35和表达猴免疫缺陷病毒Gag的新型rAd11载体的异种疫苗方案的免疫原性。正如预期的那样，异源rAd初始增强方案比同源方案具有显著的免疫原性。重要的是，所有包含rAd5的方案都被抗ad5免疫显著抑制。相比之下，rAd35-rAd11和rAd11-rAd35方案在存在和不存在抗ad5免疫的情况下都引发了高频免疫反应，尽管我们也检测到明确的交叉反应性Ad35/ ad11特异性体液和细胞免疫反应。然而，这些数据表明，使用来自罕见人类Ad血清型的载体的异源rAd启动-增强疫苗方案具有潜在的效用。
The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the immunogenicity and clinical utility of recombinant Ad5 (rAd5) vector-based vaccines for human immunodeficiency virus type I and other pathogens. A potential solution to this problem is to utilize rAd vaccine vectors derived from rare Ad serotypes such as Ad35 and Ad11. We have previously reported that rAd35 vectors were immunogenic in the presence of anti-Ad5 immunity, but the immunogenicity of heterologous rAd prime-boost regimens and the extent that cross-reactive anti-vector immunity may limit this approach have not been fully explored. Here we assess the immunogenicity of heterologous vaccine regimens involving rAd5, rAd35, and novel rAd11 vectors expressing simian immunodeficiency virus Gag in mice both with and without anti-AI15 immunity. Heterologous rAd prime-boost regimens proved significantly more immunogenic than homologous regimens, as expected. Importantly, all regimens that included rAd5 were markedly suppressed by anti-Ad5 immunity. In contrast, rAd35-rAd11 and rAd11-rAd35 regimens elicited high-frequency immune responses both in the presence and in the absence of anti-Ad5 immunity, although we also detected clear cross-reactive Ad35/Ad11-specific humoral and cellular immune responses. Nevertheless, these data suggest the potential utility of heterologous rAd prime-boost vaccine regimens using vectors derived from rare human Ad serotypes.