小柯机器人

美国国立卫生研究院Patrick E. Duffy团队揭示两种化学减毒PfSPZ疟疾疫苗诱导的无菌肝脏免疫。相关论文于2021年6月30日在线发表在《自然》杂志上。

研究人员优化了化学预防疫苗接种（CVac）的方案：无菌、纯化、冷冻保存、传染性恶性疟原虫子孢子（PfSPZ）在预防性覆盖下灌输乙胺嘧啶（PYR）（Sanaria PfSPZ-CVac(PYR)）或氯喹（CQ）（PfSPZ-CVac(CQ)），这分别杀死了肝脏阶段和血液阶段的寄生虫，并且研究人员评估了疫苗对同源（即与疫苗相同的毒株）和异源（不同毒株）免疫三个月后的人类疟疾感染（CHMI）（https://clinicaltrials.gov/，NCT02511054和NCT03083847）。

研究人员发现，PfSPZ-CVac(PYR)的剂量从 5.12×10⁴到2×10⁵ PfSPZ的四倍增加了最小的疫苗效力（低剂量，九分之二（22.2%）参与者免受同源CHMI保护），到高水平的疫苗效力，八分之七（87.5%）的个体免受同源性保护，九分之七（77.8%）的个体免受异源 CHMI 保护。增加的保护与Vδ2γδ T细胞和抗体反应有关。在较高剂量下，PfSPZ-CVac(CQ)在免疫三个月后保护六分之六（100%）参与者免受异源CHMI。所有同源（四分之四）和异源（八分之八）感染控制参与者都表现出寄生虫血症。因此，PfSPZ-CVac(CQ)和PfSPZ-CVac(PYR)诱导了针对恶性疟原虫异源南美菌株的持久无菌疫苗效力。

据悉，疟疾在全球的减少已经停滞，目前需要能够诱导持久的杀菌免疫的疫苗。

附：英文原文

Title: Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity

Author: Agnes Mwakingwe-Omari, Sara A. Healy, Jacquelyn Lane, David M. Cook, Sahand Kalhori, Charles Wyatt, Aarti Kolluri, Omely Marte-Salcedo, Alemush Imeru, Martha Nason, Lei K. Ding, Hope Decederfelt, Junhui Duan, Jillian Neal, Jacob Raiten, Grace Lee, Jen C. C. Hume, Jihyun E. Jeon, Ijeoma Ikpeama, Natasha KC, Sumana Chakravarty, Tooba Murshedkar, L. W. Preston Church, Anita Manoj, Anusha Gunasekera, Charles Anderson, Sean C. Murphy, Sandra March, Sangeeta N. Bhatia, Eric R. James, Peter F. Billingsley, B. Kim Lee Sim, Thomas L. Richie, Irfan Zaidi, Stephen L. Hoffman, Patrick E. Duffy

Issue&Volume: 2021-06-30

Abstract: The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))—which kill liver-stage and blood-stage parasites, respectively—and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) three months after immunization (https://clinicaltrials.gov/, NCT02511054 and NCT03083847). We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, two out of nine (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with seven out of eight (87.5%) individuals protected against homologous and seven out of nine (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected six out of six (100%) participants against heterologous CHMI three months after immunization. All homologous (four out of four) and heterologous (eight out of eight) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.

DOI: 10.1038/s41586-021-03684-z

Source: https://www.nature.com/articles/s41586-021-03684-z

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