Cryopreserved Sporozoites with and without the Glycolipid Adjuvant 7DW8-5 Protect in Prime-and-Trap Malaria Vaccination

接种疫苗 佐剂 病毒学 生物 环子孢子蛋白 约氏疟原虫 CD8型 免疫学 疟疾疫苗 抗原 疟疾 恶性疟原虫 寄生虫血症
作者
Felicia Watson,Melanie Shears,Jokichi Matsubara,Anya Kalata,Annette Seilie,Irene Cruz Talavera,Tayla Olsen,Moriya Tsuji,Sumana Chakravarty,B Kim Lee Sim,Stephen Hoffman,Sean Murphy
出处
期刊:American Journal of Tropical Medicine and Hygiene [American Society of Tropical Medicine and Hygiene]
标识
DOI:10.4269/ajtmh.21-1084
摘要

Repeated intravenous (IV) administration of radiation-attenuated sporozoite (RAS) vaccines induces Plasmodium-specific CD8+ liver-resident 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. Prime-and-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 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 Pyspz challenge 112 days after vaccination. Additionally, when the glycolipid adjuvant 7DW8-5 was coadministered with cryo-RAS, 7DW8-5 permitted the dose of cryo-RAS to be reduced 4-fold while still achieving high rates of sterile protection. In summary, cryo-RAS with and without 7DW8-5 were compatible with prime-and-trap malaria vaccination in a mouse model, which may accelerate the pathway for this vaccine strategy to move to NHPs and humans.

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