The Requirement for Potent Adjuvants To Enhance the Immunogenicity and Protective Efficacy of Protein Vaccines Can Be Overcome by Prior Immunization with a Recombinant Adenovirus
The Requirement for Potent Adjuvants To Enhance the Immunogenicity and Protective Efficacy of Protein Vaccines Can Be Overcome by Prior Immunization with a Recombinant Adenovirus
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DOI：
10.4049/jimmunol.1101004
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发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Draper, Simon J.
中科院分区：
文献类型：
--
作者：
de Cassan, Simone C.;Forbes, Emily K.;Draper, Simon J.
疫苗学的一个中心目标是诱导高水平和持续的抗体应答。蛋白佐剂制剂通常用来实现这种反应。然而，它们的临床开发可能受到一些最有效的临床前佐剂的反应性以及为人类使用的新佐剂许可的成本和复杂性的限制。此外，几乎没有佐剂能诱导强大的细胞免疫，这对预防许多疾病非常重要，例如疟疾。我们比较了经典佐剂(如氢氧化铝)和临床开发中的新型临床前佐剂和佐剂，如Abisco 100、CoVaccine HT、Montanide ISA720和稳定的乳剂-葡萄糖吡喃糖脂A，以了解它们诱导高和持续的抗体应答和T细胞应答的能力。这些佐剂在使用模型Ag OVA和领先的血液期疟疾疫苗候选AGS的三针蛋白佐剂方案中使用时，诱导了广泛的抗体反应。令人惊讶的是，当佐剂蛋白疫苗被用来增强由针对相同抗原的人腺病毒5型重组疫苗启动的抗体反应时，抗体免疫原性的范围大大降低。这种人腺病毒血清5型蛋白方案还诱导了更亲细胞的抗体反应，并证明了裂殖子表面蛋白-1蛋白疫苗对约氏疟原虫血期攻击的改善效果。这表明蛋白疫苗佐剂的不同免疫原性可以通过之前的重组腺病毒免疫在很大程度上被克服，特别是对于传统上被认为在亚单位疫苗背景下免疫原性较差的佐剂，并且可以避免对更有效的化学佐剂的需要。免疫学杂志，2011,187：2602-2616。
A central goal in vaccinology is the induction of high and sustained Ab responses. Protein-in-adjuvant formulations are commonly used to achieve such responses. However, their clinical development can be limited by the reactogenicity of some of the most potent preclinical adjuvants and the cost and complexity of licensing new adjuvants for human use. Also, few adjuvants induce strong cellular immunity, which is important for protection against many diseases, such as malaria. We compared classical adjuvants such as aluminum hydroxide to new preclinical adjuvants and adjuvants in clinical development, such as Abisco 100, CoVaccine HT, Montanide ISA720, and stable emulsion-glucopyranosyl lipid A, for their ability to induce high and sustained Ab responses and T cell responses. These adjuvants induced a broad range of Ab responses when used in a three-shot protein-in-adjuvant regimen using the model Ag OVA and leading blood-stage malaria vaccine candidate Ags. Surprisingly, this range of Ab immunogenicity was greatly reduced when a protein-in-adjuvant vaccine was used to boost Ab responses primed by a human adenovirus serotype 5 vaccine recombinant for the same Ag. This human adenovirus serotype 5-protein regimen also induced a more cytophilic Ab response and demonstrated improved efficacy of merozoite surface protein-1 protein vaccines against a Plasmodium yoelii blood-stage challenge. This indicates that the differential immunogenicity of protein vaccine adjuvants may be largely overcome by prior immunization with recombinant adenovirus, especially for adjuvants that are traditionally considered poorly immunogenic in the context of subunit vaccination and may circumvent the need for more potent chemical adjuvants. The Journal of Immunology, 2011, 187: 2602-2616.