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纯化灭活寨卡疫苗在猕猴中提供的完全保护:确定保护相关因素。

Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection.

机构信息

Takeda Vaccines, Inc., Cambridge, MA, USA.

Takeda Pharmaceuticals, Inc., Cambridge, MA, USA.

出版信息

Sci Rep. 2020 Feb 26;10(1):3488. doi: 10.1038/s41598-020-60415-6.

DOI:10.1038/s41598-020-60415-6
PMID:32103097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7044319/
Abstract

A critical global health need exists for a Zika vaccine capable of mitigating the effects of future Zika epidemics. In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. Indian rhesus macaques received two doses of PIZV at varying concentrations ranging from 0.016 µg - 10 µg and were subsequently challenged with ZIKV six weeks or one year following the second immunization. PIZV induced a dose-dependent immune response that was boosted by a second immunization. Complete protection against ZIKV infection was achieved with the higher PIZV doses of 0.4 µg, 2 µg, and 10 µg at 6 weeks and  with 10 ug PIZV at  1 year following vaccination. Partial protection was achieved with the lower PIZV doses of 0.016 µg and 0.08 µg. Based on these data, a neutralizing antibody response above 3.02 log EC50 was determined as a correlate of protection in macaques. PIZV elicited a dose-dependent neutralizing antibody response which is protective for at least 1 year following vaccination.

摘要

目前全球急需一种能够减轻未来寨卡病毒流行影响的寨卡疫苗。在这项研究中,我们评估了氢氧化铝佐剂的纯化灭活寨卡病毒疫苗(PIZV)对寨卡病毒(ZIKV)PRVABC59 株挑战的抗体反应和功效。印度恒河猴接受了两剂不同浓度的 PIZV 疫苗,范围从 0.016μg-10μg,随后在第二次免疫接种后 6 周或 1 年接受 ZIKV 挑战。PIZV 诱导了一种剂量依赖性的免疫反应,第二次免疫接种后得到了增强。用较高剂量的 0.4μg、2μg 和 10μg 的 PIZV 在 6 周时,以及用 10μg 的 PIZV 在 1 年时可完全预防 ZIKV 感染。用较低剂量的 0.016μg 和 0.08μg 的 PIZV 可实现部分预防。基于这些数据,在恒河猴中,中和抗体反应大于 3.02 log EC50 被确定为保护的相关性。PIZV 诱导了一种剂量依赖性的中和抗体反应,在接种疫苗后至少 1 年内具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/c86d8d0ba61b/41598_2020_60415_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/872a884262f0/41598_2020_60415_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/35dd9b618e05/41598_2020_60415_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/30ebf75bd2c7/41598_2020_60415_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/a03d5baab9b6/41598_2020_60415_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/bcdd478bc6b0/41598_2020_60415_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/c86d8d0ba61b/41598_2020_60415_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/872a884262f0/41598_2020_60415_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/35dd9b618e05/41598_2020_60415_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/30ebf75bd2c7/41598_2020_60415_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/a03d5baab9b6/41598_2020_60415_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/bcdd478bc6b0/41598_2020_60415_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5737/7044319/c86d8d0ba61b/41598_2020_60415_Fig6_HTML.jpg

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