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基于分泌型热休克蛋白 gp96-Ig-PfCA 的疟疾疫苗诱导肝内抗原特异性 CD8+T 细胞应答。

Induction of antigen specific intrahepatic CD8+ T cell responses by a secreted heat shock protein based gp96-Ig-PfCA malaria vaccine.

机构信息

Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United States.

Malaria Department, Naval Medical Research Center (NMRC), Silver Spring, MD, United States.

出版信息

Front Immunol. 2023 Mar 28;14:1130054. doi: 10.3389/fimmu.2023.1130054. eCollection 2023.

DOI:10.3389/fimmu.2023.1130054
PMID:37056783
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10086177/
Abstract

INTRODUCTION

A highly efficacious and durable vaccine against malaria is an essential tool for global malaria eradication. One of the promising strategies to develop such a vaccine is to induce robust CD8+ T cell mediated immunity against malaria liver-stage parasites.

METHODS

Here we describe a novel malaria vaccine platform based on a secreted form of the heat shock protein, gp96-immunoglobulin, (gp96-Ig) to induce malaria antigen specific, memory CD8+ T cells. Gp96-Ig acts as an adjuvant to activate antigen presenting cells (APCs) and chaperone peptides/antigens to APCs for cross presentation to CD8+ T cells.

RESULTS

Our study shows that vaccination of mice and rhesus monkeys with HEK-293 cells transfected with gp96-Ig and two well-known CSP and AMA1 (PfCA) vaccine candidate antigens, induces liver-infiltrating, antigen specific, memory CD8+ T cell responses. The majority of the intrahepatic CSP and AMA1 specific CD8+ T cells expressed CD69 and CXCR3, the hallmark of tissue resident memory T cells (Trm). Also, we found intrahepatic, antigen-specific memory CD8+ T cells secreting IL-2, which is relevant for maintenance of effective memory responses in the liver.

DISCUSSION

Our novel gp96-Ig malaria vaccine strategy represents a unique approach to induce liver-homing, antigen-specific CD8+ T cells critical for liver-stage protection.

摘要

简介

一种高效且持久的疟疾疫苗是全球疟疾消除的重要工具。开发此类疫苗的一种有前途的策略是诱导针对疟疾肝期寄生虫的强大 CD8+T 细胞介导的免疫。

方法

在这里，我们描述了一种基于热休克蛋白 gp96-免疫球蛋白（gp96-Ig）的新型疟疾疫苗平台，以诱导疟疾抗原特异性、记忆 CD8+T 细胞。gp96-Ig 作为佐剂激活抗原呈递细胞（APC），并将肽/抗原伴侣到 APC 进行交叉呈递以激活 CD8+T 细胞。

结果

我们的研究表明，用 HEK-293 细胞转染的 gp96-Ig 和两种众所周知的 CSP 和 AMA1（PfCA）疫苗候选抗原对小鼠和恒河猴进行疫苗接种，可诱导肝浸润、抗原特异性、记忆 CD8+T 细胞反应。大多数肝内 CSP 和 AMA1 特异性 CD8+T 细胞表达 CD69 和 CXCR3，这是组织驻留记忆 T 细胞（Trm）的标志。此外，我们发现肝内抗原特异性记忆 CD8+T 细胞分泌 IL-2，这对于维持肝内有效记忆反应很重要。

讨论

我们的新型 gp96-Ig 疟疾疫苗策略代表了一种诱导关键的肝归巢、抗原特异性 CD8+T 细胞的独特方法，这对于肝期保护至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/00664070c596/fimmu-14-1130054-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/a0707d75e710/fimmu-14-1130054-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/84257d0c56be/fimmu-14-1130054-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/f8dc53a2e81c/fimmu-14-1130054-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/2ab18d31ab7c/fimmu-14-1130054-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/b246f40b688b/fimmu-14-1130054-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/00664070c596/fimmu-14-1130054-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/a0707d75e710/fimmu-14-1130054-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/84257d0c56be/fimmu-14-1130054-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/f8dc53a2e81c/fimmu-14-1130054-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/2ab18d31ab7c/fimmu-14-1130054-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/b246f40b688b/fimmu-14-1130054-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efa8/10086177/00664070c596/fimmu-14-1130054-g006.jpg

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本文引用的文献

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2
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3
Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice.诱导 gp96-Ig-S 疫苗接种小鼠肺部的 SARS-CoV-2 蛋白 S 特异性 CD8+ T 细胞。
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4
A guide to vaccinology: from basic principles to new developments.疫苗学指南：从基本原则到新进展。
Nat Rev Immunol. 2021 Feb;21(2):83-100. doi: 10.1038/s41577-020-00479-7. Epub 2020 Dec 22.
5
A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naive Adults.一项在疟疾初治成年人中开展的 RTS,S/AS01E 和 RTS,S/AS01B 延迟部分剂量方案的 IIa 期对照人体疟疾感染和免疫原性研究。
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