Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination
Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination
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DOI：
10.4269/ajtmh.21-1084
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发表时间：
2022-04-01
影响因子：
3.3
通讯作者：
Murphy, Sean
中科院分区：
文献类型：
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作者：
Watson, Felicia;Shears, Melanie;Murphy, Sean
反复静脉注射辐射减毒的子孢子虫(RAS)疫苗可诱导小鼠体内的疟原虫特异性CD8(+)肝脏驻留记忆T(Trm)细胞，并实现对攻击的无菌保护。我们的异源“优质和陷阱”疫苗策略以前被证明可以简化和改进RAS疫苗接种。Primeand-Trap疫苗结合了DNA编码的环子孢子蛋白(CSP)抗原和单次静脉注射新鲜解剖的RAS(Fresh-RAS)来引导和捕获肝脏中激活和扩张的CD8(+)T细胞。初始和陷阱免疫可保护小鼠免受野生型子孢子(SPZ)攻击。如果新鲜的RAS可以被冷冻保存的RAS(低温RAS)取代，那么在非人类灵长类动物(NHP)模型和/或人类中评估初级和陷阱疫苗将是非常可能的。在这里，我们研究了是否可以用冷冻RAS替代新鲜RAS在BALB/CJ小鼠中进行基础和陷阱疫苗接种。尽管低温RAS接种后SPZ疫苗的肝脏负担与新鲜RAS相比有所降低，但低温RAS诱导了相似水平的约氏疟原虫(Py)CSP特异性CD8(+)肝Trm细胞，并在接种112天后完全保护小鼠免受Py SPZ攻击。此外，当糖脂佐剂7DW8-5与冷冻-RAS联合使用时，7DW8-5允许冷冻-RAS的剂量减少四倍，同时仍获得高无菌保护率。总之，在小鼠模型中，使用和不使用7DW8-5的低温RAS与原始捕获疟疾疫苗是相容的，这可能会加速这种疫苗策略转移到NHP和人类的途径。
Repeated intravenous (IV) administration of radiation-attenuated sporozoite (RAS) vaccines induces Plasmodium-specific CD8(+) liver-resident memory T (Trm) cells in mice and achieves sterile protection against challenge. Our heterologous "prime-and-trap" vaccine strategy was previously shown to simplify and improve upon RAS vaccination. Primeand-trap vaccination combines epidermal priming by DNA-encoded circumsporozoite protein (CSP) antigen followed by a single IV dose of freshly dissected RAS (fresh-RAS) to direct and trap activated and expanding CD8(+) T cells in the liver. Prime-and-trap vaccination protects mice against wild-type sporozoite (spz) challenge. Assessment of prime-and-trap vaccines in nonhuman primate (NHP) models and/or humans would be greatly enabled if fresh-RAS could be replaced by cryopreserved RAS (cryo-RAS). Here, we investigated if fresh-RAS could be replaced with cryo-RAS for prime-and-trap vaccination in BALB/cj mice. Despite a reduction in spz vaccine liver burden following cryo-RAS administration compared with fresh-RAS, cryo-RAS induced a similar level of Plasmodium yoelii (Py) CSP-specific CD8(+) liver Trm cells and completely protected mice against Py spz challenge 112 days after vaccination. Additionally, when the glycolipid adjuvant 7DW8-5 was co-administered with cryo-RAS, 7DW8-5 permitted the dose of cryo-RAS to be reduced four-fold while still achieving high rates of sterile protection. In summary, cryo-RAS with and without 7DW8-5 were compatible with primeand-trap malaria vaccination in a mouse model, which may accelerate the pathway for this vaccine strategy to move to NHPs and humans.