A SYNTHETIC PEPTIDE INDUCES LONG-TERM PROTECTION FROM LETHAL INFECTION WITH HERPES-SIMPLEX VIRUS-2
A SYNTHETIC PEPTIDE INDUCES LONG-TERM PROTECTION FROM LETHAL INFECTION WITH HERPES-SIMPLEX VIRUS-2
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DOI：
10.1084/jem.165.2.459
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发表时间：
1987-02-01
影响因子：
15.3
通讯作者：
HEBERKATZ, E
中科院分区：
文献类型：
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作者：
WATARI, E;DIETZSCHOLD, B;HEBERKATZ, E
针对病毒病原体的免疫接种通常针对病毒中和抗体（VNA）的诱导和第二组（IgG）应答的可能性的维持。事实上，特异性抗体水平的升高被认为是宿主中存在免疫状态的可靠临床指标。然而，在单纯疱疹病毒（HSV）的情况下，循环VNA的存在并不一定与保护相关。因此，已经发现，即使对HSV具有高中和滴度的个体也会发生继发感染，这表明病毒的抗体可能是无用的甚至是有害的。考虑到这些事实，我们对诱导T细胞对HSV的应答感兴趣。我们已经证明，当注射到小鼠体内时，对应于HSV糖蛋白D（gD）分子的NH 3末端区域的合成肽可以诱导强烈的T细胞应答，但其本身并不赋予保护作用。在这份报告中，我们研究了肽的能力，共价偶联到棕榈酸，并纳入脂质体，诱导病毒特异性T细胞反应，赋予对HSV-2的致命挑战的保护。我们已经证明，当抗原以这种形式呈递时，在不存在中和抗体的情况下，单次免疫可实现长期保护性免疫。此外，T细胞，而不是血清从这样的免疫小鼠可以过继转移这种保护。
Immunization against viral pathogens is generally directed toward the induction of virus neutralizing antibody (VNA) and the maintenance of the potential for a second-set (IgG) response. Indeed, an elevated level of specific antibody is considered a reliable clinical indicator that a state of immunity exists in the host. However, in the case of herpes simplex virus (HSV), the presence of circulating VNA does not necessarily correlate with protection. Thus, it has been found that secondary infections occur in individuals even with high neutralizing titers to HSV, suggesting that antibody to the virus may be useless or even deleterious. In consideration of these facts, we were interested in inducing a T cell response to HSV. We have already shown that synthetic peptides corresponding to the NH3-terminal region of the glycoprotein D (gD) molecule of HSV could induce a strong T cell response when injected into mice, but did not, by themselves, confer protection. In this report, we examined the ability of peptides, covalently coupled to palmitic acid and incorporated into liposomes, to induce virus-specific T cell responses that confer protection against a lethal challenge of HSV-2. We have demonstrated that long-term protective immunity is achieved with a single immunization in the absence of neutralizing antibody when antigen is presented in this form. Furthermore, T cells but not serum from such immune mice can adoptively transfer this protection.