病毒逃生突变不能解释RhCMV/SIV接种疫苗的 rhesus macaques 对SIVmac239的挑战缺乏保护
Benjamin N Bimber1,2, Justine Sunshine2, G W McElfresh1
1Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United States.
Frontiers in immunology
|August 22, 2024
概括
rhesus Cytomegalovirus (RhCMV) 疫苗可以保护一些 rhesus macaques (RMs) 免受 Simian 免疫缺陷病毒 (SIV) 的感染. 病毒突变不能解释为什么一些接种疫苗的RM无法控制SIV感染.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 疫苗学 疫苗学 疫苗学
背景情况:
- 使用 rhesus cytomegalovirus (RhCMV) 载体的类似免疫缺陷病毒 (SIV) 疫苗在 rhesus macaques (RMs) 中显示出显著的保护.
- 大约60%的接种疫苗的RM实现了完全的SIVmac239复制停止,而其他人则经历了渐进的感染.
- 在未受保护的RM中感染控制失败背后的机制需要调查.
研究的目的:
- 调查病毒逃生突变是否解释了RhCMV/SIV疫苗接种的RM中SIV控制的缺乏.
- 在挑战后分析受保护和不受保护的RMS病毒测序数据.
- 评估疫苗接种对慢性感染期间病毒突变模式的影响.
主要方法:
- 挑战后从 rhesus macaques (RMs) 获得的 Simian 免疫缺陷病毒 (SIV) 的病毒测序.
- 接种疫苗和未接种疫苗的控制RM之间的病毒突变模式的比较.
- 针对RhCMV/SIV和正规MHC-Ia表位的表位突变的分析.
主要成果:
- 在挑战后28天内,所有动物都积累了低水平的病毒突变.
- 在未接种疫苗的RM群中,流传的病毒几乎与挑战群相同,与未接种疫苗的对照群没有差异.
- 在受保护和未受保护的疫苗接种MR或未接种疫苗的对照组之间没有观察到突变模式的差异.
- 接种疫苗的RM在慢性感染期间没有在向表位上获得逃生突变,但在正规的MHC-Ia表位上显示出与未接种疫苗的RM相似的突变.
结论:
- 病毒突变并不能解释未能控制 rhesus macaques (RMs) 中的 Simian 免疫缺陷病毒 (SIV) 复制,因为它们不受 RhCMV/SIV 疫苗接种的保护.
- 疫苗接种引起的非传统的T细胞反应不会在初始控制失败后对系统复制SIV施加强烈的选择性压力.
- 需要进一步的研究,以了解导致RhCMV/SIV疫苗观察到的可变保护的因素.
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