A chemically defined synthetic vaccine model for HIV-1.
A chemically defined synthetic vaccine model for HIV-1.
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DOI：
10.4049/jimmunol.148.3.914
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发表时间：
1992-02
影响因子：
4.4
通讯作者：
B. Nardelli;Y. A. Lu;D. R. Shiu;C. Delpierre-Defoort;A. Profy;J. Tam
中科院分区：
文献类型：
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作者：
B. Nardelli;Y. A. Lu;D. R. Shiu;C. Delpierre-Defoort;A. Profy;J. Tam
不使用蛋白载体的多抗原肽（MAP）系统被用作三种动物的疫苗模型。将来自IIIB、RF和MN HIV-1分离物的gp 120的V3区的合成肽用作Ag。MAP由11至24个残基的各种链长组成，以含有每个单独肽的四个重复的单表位构型制备。平行地，它们以双表位构型合成，在V3肽的羧基末端添加保守序列，已知为gp 120的Th细胞表位。单表位构建体引发的抗体反应具有物种依赖性。兔产生的免疫力对所有九种肽，而小鼠强烈反应主要是最长的序列的IIIB分离。豚鼠的免疫应答介于家兔和小鼠之间。双表位MAPs在所有三个物种中具有免疫原性，并且引起的滴度显著高于用单表位MAPs免疫所引起的滴度。反应是类型特异性的;高滴度抗体主要对肽衍生的分离株具有反应性，在ELISA中IIIB和RF菌株之间具有小的交叉反应性。B细胞表位的优势抗原位点IIIB序列位于MAP的氨基和中心部分，并且与推定的V3反向转角重叠的序列与产生的抗体特别反应。此外，来自免疫动物的血清抑制病毒依赖性细胞融合。这些结果表明，MAP，具有化学上确定的结构和不使用蛋白质载体，可以是潜在的有用的合成HIV-1候选疫苗的设计。
Multiple Ag peptide (MAP) system without the use of a protein carrier was used as a vaccine model in three species of animals. Synthetic peptides from the V3 region of the gp120 of IIIB, RF and MN HIV-1 isolates were used as the Ag. MAP consisting of various chain lengths, from 11 to 24 residues, were prepared in a monoepitope configuration containing four repeats of each individual peptide. In parallel, they were synthesized in a diepitope configuration adding at the carboxyl-terminus of the V3 peptides a conserved sequence, known to be a Th cell epitope of gp120. The antibody response elicited by the monoepitope constructs was species-dependent. Rabbits produced immunity against all nine peptides, whereas mice were strongly reactive mainly to the longest sequence of the IIIB isolate. The immune response of guinea pigs was intermediate to those of rabbits and mice. Diepitope MAPs were immunogenic in all three species and elicited significantly higher titers than those raised by the immunization with the monoepitope MAPs. The response was type specific; the high-titered antibodies were reactive mostly against the isolate from which the peptides were derived, with a small cross-reactivity in ELISA between IIIB and RF strains. The dominant antigenic site of the B cell epitope, IIIB sequence, was located at the amino and central part of the MAP and a sequence overlapping the putative V3 reverse-turn was particularly reactive with the raised antibodies. Moreover, sera from the immunized animals inhibited virus-dependent cell fusion. These results show that MAP, with a chemically defined structure and without the use of a protein carrier, can be potentially useful for the design of synthetic HIV-1 vaccine candidates.