Vaccination against γ-herpesviruses has proved difficult. CD4+ T cells are essential to contain infection, but how best to prime them and whether this can reduce viral loads remain unclear. To address these questions, we used ovalbumin (OVA) as a model antigen, delivering it with murine cytomegalovirus (MCMV) to protect mice against OVA-expressing murine herpesvirus-4 (MuHV-4). Membrane-associated OVA (mOVA) was more effective than soluble OVA, both to prime CD4+ T cells and as an effector target. It was also a better target than an OVA epitope limited to infected cells, suggesting that protective CD4+ T cells recognize infected cell debris rather than infected cells themselves. While MCMV-mOVA protected acutely against MuHV-4-mOVA, long-term protection was incomplete, even when OVA-specific CD8+ T cells and B cells were also primed. Thus, even optimized single-target vaccines may poorly reduce long-term γ-herpesvirus infections.

中文翻译：

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模型CD4 + T细胞疫苗抗原的膜缔合可增强针对鼠疱疹病毒4感染的保护，但保护作用不完全。

事实证明，针对γ-疱疹病毒的疫苗接种非常困难。CD4 + T细胞对于遏制感染至关重要，但是如何最好地引发它们以及是否可以减少病毒载量尚不清楚。为了解决这些问题，我们使用卵清蛋白（OVA）作为模型抗原，将其与鼠巨细胞病毒（MCMV）一起递送，以保护小鼠免受表达OVA的鼠疱疹病毒4（MuHV-4）的侵害。膜相关的OVA（mOVA）比可溶性OVA更有效，既可启动CD4 + T细胞，又可作为效应子靶标。与仅限于感染细胞的OVA表位相比，它也是更好的靶标，表明保护性CD4 + T细胞识别感染的细胞碎片而不是感染的细胞本身。尽管MCMV-mOVA可以针对MuHV-4-mOVA进行急性保护，但即使OVA特异性CD8 + T细胞和B细胞也已启动，长期保护仍不完全。从而，