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Impact of Vector Priming on the Immunogenicity of Recombinant Salmonella Vaccines

机译：载体启动对重组沙门氏菌疫苗免疫原性的影响

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There are conflicting reports concerning the impact of prior vector priming on the immunogenicity of recombinant-Salmonella-based vaccines. A comparison of experimental protocols identified two variables which might account for this inconsistency: the potential of the vector strain to colonize the murine gut-associated lymphoid tissue (GALT) and the nature of the foreign antigen subsequently delivered by the recombinant Salmonella construct. The former was investigated by constructing an aroA mutant of the Salmonella enterica serovar Stanley vector previously used in our laboratory. Although the introduction of an aroA mutation had surprisingly little effect on GALT colonization, it did reduce the strength of antilipopolysaccharide (anti-LPS) antibody responses and the impact of vector priming. Studies were also performed to ascertain the extent to which any observed hyporesponsiveness consequent upon vector priming might be determined by the characteristics of the foreign antigen. S. enterica serovar Stanley was used to deliver either of two Escherichia coli antigens, K88 pilus protein or the LT-B toxin subunit, to vector-primed mice. Both serum immunoglobulin G (IgG) and intestinal IgA responses to K88 were completely abolished, and those to LT-B were significantly reduced, as a consequence of vector priming. When similar experiments were performed with an aroA S. enterica serovar Dublin vector, responses to K88 were significantly reduced but those to LT-B were unaffected by vector priming. Paradoxically, a priming infection with this vector induced stronger anti-LPS antibody responses but was less likely to elicit a state of hyporesponsiveness to subsequently presented foreign antigen. The impact of vector priming thus depends on both the Salmonella strain used and the nature of the foreign antigen, but our present data strengthen concerns that preexisting antivector immunity represents a serious threat to the Salmonella-based vaccine strategy.
机译：关于先前载体启动对基于重组沙门氏菌的疫苗的免疫原性影响的报道相互矛盾。实验方案的比较确定了两个可能导致这种不一致的变量：载体菌株在鼠肠道相关淋巴样组织（GALT）中定殖的潜力以及重组沙门氏菌随后传递的外来抗原的性质/ em>构造。前者是通过构建先前在我们实验室中使用的 Salmonella enterica 血清型Stanley载体的 aroA 突变体进行研究的。尽管引入 aroA 突变对GALT定植几乎没有影响，但它确实降低了抗脂多糖（anti-LPS）抗体应答的强度以及载体引发的影响。还进行了研究以确定在载体引发后所观察到的任何反应不足的程度都可以由外源抗原的特征确定的程度。 S。用Enterica 血清型Stanley将两种大肠杆菌抗原（K88菌毛蛋白或LT-B毒素亚基）递送给载体致敏的小鼠。由于载体启动，血清免疫球蛋白G（IgG）和肠道IgA对K88的反应均被完全消除，而对LT-B的反应明显降低。用 aroA S.enterica 血清型都柏林载体进行类似实验时，对K88的应答显着降低，但对LT-B的应答不受载体引发的影响。矛盾的是，用该载体引发的初次感染诱导了更强的抗-LPS抗体反应，但不太可能引起对随后呈递的外源抗原的低反应状态。因此，载体引发的影响既取决于所使用的沙门氏菌菌株，也取决于外来抗原的性质，但是我们目前的数据更加令人担忧，即预先存在的抗载体免疫力对沙门氏菌构成严重威胁。基于em>的疫苗策略。

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