Carbopol dispersed PAA-modified UIO-66 with high colloidal stability as a combination nano-adjuvant boosts immune response and protection against pseudorabies virus in mice and pigs

作者全名："Liao, Xiaoling; Nie, Jingjing; Yuan, Xiangyang; Feng, Zhao; Cui, Endian; Wu, Yang; Li, Yuan; Scherman, Daniel; Liu, Yingshuai"

作者地址："[Liao, Xiaoling; Yuan, Xiangyang; Cui, Endian; Liu, Yingshuai] Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China; [Nie, Jingjing; Feng, Zhao; Wu, Yang] Sinopharm Anim Hlth Co Ltd, Adjuvant Res Lab, Wuhan 430073, Peoples R China; [Li, Yuan] Chongqing Med Univ, Cent Lab, Yongchuan Hosp, Chongqing 402160, Peoples R China; [Scherman, Daniel] Univ Paris Cite, CNRS, Unite Technol Chim & Biol Sante, INSERM,UTCBS, F-75006 Paris, France"

通信作者："Liu, YS (通讯作者)，Southwest Univ, Sch Mat & Energy, Key Lab Luminescence Anal & Mol Sensing, Minist Educ, Chongqing 400715, Peoples R China.; Wu, Y (通讯作者)，Sinopharm Anim Hlth Co Ltd, Adjuvant Res Lab, Wuhan 430073, Peoples R China.; Li, Y (通讯作者)，Chongqing Med Univ, Cent Lab, Yongchuan Hosp, Chongqing 402160, Peoples R China."

来源：ACTA BIOMATERIALIA

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001062192900001

JCR分区：Q1

影响因子：9.4

年份：2023

卷号：168

期号：　

开始页：540

结束页：550

文献类型：Article

关键词：Metal-organic framework; Nano-adjuvant; Immune response; Pseudorabies virus

摘要："Although inactivated vaccines have higher safety than live-attenuated vaccines in the control of pseudorabies virus (PRV), their protection efficacy is limited due to insufficient immunogenicity when used alone. High-performance adjuvants that can potentiate immune responses are highly desirable to improve the protection efficacy of inactivated vaccines. In this work, we have developed U@PAA-Car, a Carbopol dispersed zirconium-based metal-organic framework UIO-66 modified by polyacrylic acid (PAA), as a promising adjuvant for inactivated PRV vaccines. The U@PAA-Car has good biocompatibility, high colloidal stability, and antigen (vaccine) loading capacity. It significantly potentiates humoral and cellular immune responses over either U@PAA, Carbopol, or commercial adjuvants such as Alum and biphasic 201 by inducing a higher specific antibody titer, IgG2a/IgG1 ratio, cell cytokine secretion, and splenocyte proliferation. A protection rate of over 90% was observed in challenge tests in the model animal mice and the host animal pigs, which is much higher than that observed with commercial adjuvants. The high performance of the U@PAA-Car is attributed to antigen sustainable release at the injection site and highly efficient antigen internalization and presentation. In conclusion, this work not only demonstrates a great potential of the developed U@PAA-Car nano-adjuvant for the inactivated PRV vaccine but also gives a preliminary explanation of its action mechanism.Statement of significanceWe have developed a Carbopol dispersed PAA-modified zirconium-based metal-organic framework UIO-66 (U@PAA-Car) as a promising combination nano-adjuvant for the inactivated PRV vaccine. The U@PAA-Car induced higher specific antibody titers and IgG2a/IgG1 ratio, increased cell cytokines secretion, and better splenocyte proliferation than U@PAA, Carbopol, and the commercial adjuvants Alum and biphasic 201, indicating that it induces a significant potentiation of humoral and cellular immune response. In addition, much higher protection rates were achieved with the U@PAA-Car-adjuvanted PRV vaccine in mice and pigs challenge than those observed from the commercial adjuvant groups. This work not only demonstrates the great potential of the U@PAA-Car nano-adjuvant in an inactivated PRV vaccine but also gives a preliminary explanation of its action mechanism.& COPY; 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved."

基金机构："3551 Optics Valley Innovative Talent Program in 2021 (Wuhan, Hubei); Chongqing Engineering Research Center for Rapid Diagnosis of Dread Disease; Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices , Southwest University, China"

基金资助正文："This research was supported by the 3551 Optics Valley Innovative Talent Program in 2021 (Wuhan, Hubei), Chongqing Engineering Research Center for Rapid Diagnosis of Dread Disease and Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices , Southwest University, China."