Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models
Arthritogenic Alphavirus Vaccines: Serogrouping Versus Cross-Protection in Mouse Models
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DOI：
10.3390/vaccines8020209
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发表时间：
2020-06-01
期刊：
影响因子：
7.8
通讯作者：
Suhrbier, Andreas
中科院分区：
文献类型：
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作者：
Nguyen, Wilson;Nakayama, Eri;Suhrbier, Andreas
基孔肯雅病毒（CHIKV）、罗斯河病毒（RRV）、奥尼扬病毒（ONNV）、马亚罗病毒（MAYV）和盖塔病毒（GETV）代表属于塞姆利基森林病毒抗原复合物的致关节炎甲病毒。针对这些病毒之一产生的抗体可以与其他血清组成员交叉反应，这表明，例如，CHIKV疫苗（被认为是商业上可行的）可能提供针对抗原相关甲病毒的交叉保护。在此，我们使用人甲病毒分离株（包括一种新的人RRV分离株）和野生型小鼠来探索在用抗原复合物的其他成员攻击后，一种病毒的感染是否导致针对病毒血症的交叉保护。还使用持续感染的Ragl（-/-）小鼠来评估恢复期CHIKV血清的交叉保护能力。我们还评估了重组痘病毒基CHIKV疫苗和市售福尔马林固定的全病毒GETV疫苗诱导交叉保护性应答的能力。尽管交叉保护和/或交叉反应性是明显的，但它们不是普遍的，并且通常是次优的。甚至对于更密切相关的病毒（例如，对于针对预期同源靶标的疫苗介导的中和和/或保护（例如，针对CHIKV和ONNV，或RRV和GETV），疫苗介导的针对预期同源靶标的中和和/或保护比针对异源病毒的交叉中和和/或交叉保护显著更有效。因此，有效的疫苗介导的交叉保护可能需要更高的剂量和/或更多的疫苗接种，这可能对监管机构和疫苗制造商没有吸引力。
Chikungunya virus (CHIKV), Ross River virus (RRV), o'nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex. Persistently infected Rag1(-/-)mice were also used to assess the cross-protective capacity of convalescent CHIKV serum. We also assessed the ability of a recombinant poxvirus-based CHIKV vaccine and a commercially available formalin-fixed, whole-virus GETV vaccine to induce cross-protective responses. Although cross-protection and/or cross-reactivity were clearly evident, they were not universal and were often suboptimal. Even for the more closely related viruses (e.g., CHIKV and ONNV, or RRV and GETV), vaccine-mediated neutralization and/or protection against the intended homologous target was significantly more effective than cross-neutralization and/or cross-protection against the heterologous virus. Effective vaccine-mediated cross-protection would thus likely require a higher dose and/or more vaccinations, which is likely to be unattractive to regulators and vaccine manufacturers.