A genetically engineered neuronal membrane-based nanotoxoid elicits protective immunity against neurotoxins  

作　　者：Zhongyuan Guo Audrey T.Zhu Xiaoli Wei Yao Jiang Yiyan Yu Ilkoo Noh Weiwei Gao Ronnie H.Fang Liangfang Zhang 

机构地区：[1]Department of NanoEngineering,Chemical Engineering Program,Shu and K.C.Chien and Peter Farrell Collaboratory,University of California San Diego,La Jolla,CA,92093,USA [2]Division of Host-Microbe Systems and Therapeutics,Department of Pediatrics,University of California San Diego,La Jolla,CA,92093,USA

出　　处：《Bioactive Materials》2024年第8期321-330,共10页生物活性材料（英文）

基　　金：supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense under award number HDTRA1-21-1-0010;the National Institutes of Health under Award Numbers R21AI159492 and R21AI175904.

摘　　要：Given their dangerous effects on the nervous system,neurotoxins represent a significant threat to public health.Various therapeutic approaches,including chelating agents,receptor decoys,and toxin-neutralizing antibodies,have been explored.While prophylactic vaccines are desirable,it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins.To address this,we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles.A genetically modified cell line with constitutive overexpression of theα7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind toα-bungarotoxin,a model neurotoxin.This abrogates the biological activity of the toxin,enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system.When co-administered with an immunological adjuvant,a strong humoral response againstα-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin.Overall,this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.

关 键 词：Antivirulence vaccine Cell membrane-coated nanoparticle Genetic engineering Α-BUNGAROTOXIN Nanotoxoid 

分 类 号：R741[医药卫生—神经病学与精神病学]