A conformational C4 peptide polymer vaccine coupled with live recombinant vector priming is immunogenic but does not protect against rectal SIV challenge.
A conformational C4 peptide polymer vaccine coupled with live recombinant vector priming is immunogenic but does not protect against rectal SIV challenge.
复制标题
构象 C4 肽聚合物疫苗与活重组载体引发相结合具有免疫原性，但不能防止直肠 SIV 攻击。
DOI：
10.1089/088922201750252034
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发表时间：
2001
影响因子：
1.5
通讯作者：
Robert-Guroff,M
中科院分区：
文献类型：
--
作者：
Patterson,LJ;Robey,F;Muck,A;VanRemoortere,K;Aldrich,K;Richardson,E;Alvord,WG;Markham,PD;Cranage,M;Robert-Guroff,M
病毒包膜上保守的、免疫原性的 CD4 结合位点是一种有吸引力的 HIV 或 SIV 候选疫苗。衍生自 SIV gp120 的 C4 结构域的 18 个氨基酸片段的聚合产生了肽聚合物或“peptomer”，其具有可能模仿未结合天然蛋白中 C4 结构域的拟议结构的 α-螺旋构象。在两次 5 型腺病毒宿主范围 (Ad5hr)-SIVenv 重组引发免疫后，将 SIV 肽聚体和天然 gp120 作为亚单位加强进行比较。两种疫苗方案均成功在六只免疫猕猴中的五只中引发了 SIV 特异性 CTL 反应。 Peptomer 增强的猕猴表现出比 gp120 增强的猕猴或对照猕猴显着更高的包膜特异性 T 细胞增殖反应。 Peptomer 免疫也引发了 peptomer 和 SIV gp120 特异性结合抗体，但仅天然 gp120 加强引发了 SIV 中和抗体。在用 SIVmac32H 进行直肠内攻击后，所有九只猕猴都被感染。仅基于包膜的疫苗无法提供保护。然而，将增强免疫原改为 C4 肽聚体并没有提高保护功效，尽管它能引发体液和细胞免疫反应，包括强大的 T 辅助活性。尽管肽体具有很强的免疫原性和诱导广泛保护性免疫反应的潜力，但它作为亚单位疫苗并不有效。
The conserved, immunogenic CD4 binding site on the viral envelope is an attractive HIV or SIV vaccine candidate. Polymerization of an 18 amino acid segment derived from the C4 domain of SIV gp120 produced a peptide polymer or "peptomer," having anα-helical conformation possibly mimicking a proposed structure of the C4 domain in the unbound native protein. The SIV peptomer and native gp120 were compared as subunit boosts following two adenovirus type 5 host range (Ad5hr)-SIVenv recombinant priming immunizations. Both vaccine regimens successfully elicited SIV-specific CTL responses in five of six immunized macaques. Peptomer-boosted macaques exhibited significantly higher envelope-specific T cell proliferative responses than either the gp120-boosted macaques or controls. Peptomer immunization also elicited peptomer and SIV gp120-specific binding antibodies, but only native gp120 boosting elicited SIV neutralizing antibodies. Upon intrarectal challenge with SIVmac32H, all nine macaques became infected. The solely envelope-based vaccine conferred no protection. However, changing the boosting immunogen to the C4 peptomer did not improve protective efficacy in spite of its elicitation of humoral and cellular immune responses, including robust T-helper activity. In spite of the peptomer's strong immunogenicity and potential for induction of broadly protective immune responses, it was not effective as a subunit vaccine.