Cytos Biotechnology AG, Wagistr. 25, 8952 Zürich-Schlieren, Switzerland.
Vaccine. 2010 Jul 26;28(33):5503-12. doi: 10.1016/j.vaccine.2010.02.103. Epub 2010 Mar 20.
Pre-existing immunity against vaccine carrier proteins has been reported to inhibit the immune response against antigens conjugated to the same carrier by a process termed carrier induced epitopic suppression (CIES). Hence understanding the phenomenon of CIES is of major importance for the development of conjugate vaccines. Virus-like particles (VLPs) are a novel class of potent immunological carriers which have been successfully used to enhance the antibody response to virtually any conjugated antigen. In the present study we investigated the impact of a pre-existing VLP-specific immune response on the development of antibody responses against a conjugated model peptide after primary, secondary and tertiary immunization. Although VLP-specific immune responses led to reduced peptide-specific antibody titers, we showed that CIES against peptide-VLP conjugates could be overcome by high coupling densities, repeated injections and/or higher doses of conjugate vaccine. Furthermore we dissected VLP-specific immunity by adoptively transferring VLP-specific antibodies, B-cells or T(helper) cells separately into naïve mice and found that the observed CIES against peptide-VLP conjugates was mainly mediated by carrier-specific antibodies.
已有研究报道称，针对疫苗载体蛋白的预先存在的免疫会抑制与同一载体偶联的抗原的免疫反应，这一过程被称为载体诱导表位抑制（CIES）。因此，了解 CIES 现象对于结合疫苗的开发至关重要。病毒样颗粒（VLPs）是一类新型有效的免疫载体，已成功用于增强对几乎任何偶联抗原的抗体反应。在本研究中，我们研究了预先存在的 VLP 特异性免疫反应对初次、二次和三次免疫后针对共轭模型肽的抗体反应发展的影响。尽管 VLP 特异性免疫反应导致肽特异性抗体滴度降低，但我们表明，通过高偶联密度、重复注射和/或更高剂量的结合疫苗，可以克服针对肽-VLP 结合物的 CIES。此外，我们通过将 VLP 特异性抗体、B 细胞或 T（辅助）细胞分别过继转移到 naive 小鼠中，对 VLP 特异性免疫进行了剖析，结果发现针对肽-VLP 结合物的观察到的 CIES 主要是由载体特异性抗体介导的。
