Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice

We previously explored a panel of adjuvants formulated with pre-fusion RSV-F protein and found that AS02 may be a promising candidate adjuvant for developing RSV-F subunit vaccines with improved immunogenicity and desired immune response type. In this study, we performed a head-to-head comparison of...

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Main Authors: Lijun Bian, Yu Zheng, Xiaohong Guo, Dongdong Li, Jingying Zhou, Linyao Jing, Yan Chen, Jingcai Lu, Ke Zhang, Chunlai Jiang, Yong Zhang, Wei Kong
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.938598/full
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author Lijun Bian
Yu Zheng
Xiaohong Guo
Dongdong Li
Jingying Zhou
Linyao Jing
Yan Chen
Yan Chen
Yan Chen
Jingcai Lu
Ke Zhang
Chunlai Jiang
Chunlai Jiang
Chunlai Jiang
Chunlai Jiang
Yong Zhang
Yong Zhang
Yong Zhang
Wei Kong
Wei Kong
Wei Kong
Wei Kong
author_facet Lijun Bian
Yu Zheng
Xiaohong Guo
Dongdong Li
Jingying Zhou
Linyao Jing
Yan Chen
Yan Chen
Yan Chen
Jingcai Lu
Ke Zhang
Chunlai Jiang
Chunlai Jiang
Chunlai Jiang
Chunlai Jiang
Yong Zhang
Yong Zhang
Yong Zhang
Wei Kong
Wei Kong
Wei Kong
Wei Kong
author_sort Lijun Bian
collection DOAJ
description We previously explored a panel of adjuvants formulated with pre-fusion RSV-F protein and found that AS02 may be a promising candidate adjuvant for developing RSV-F subunit vaccines with improved immunogenicity and desired immune response type. In this study, we performed a head-to-head comparison of the effect of intramuscular injection to that of subcutaneous injection on the immune response and protective efficacy of recombinant RSV-F subunit vaccine with or without adjuvants (Alhydrogel, squalene-based emulsion adjuvants MF59, AS03, and AS02) in BALB/c mice. After inoculations, antigen-specific antibodies, neutralizing antibodies, antibody subtypes, cytokines, and the persistence of immune response were evaluated. Moreover, challenge tests were also performed to illustrate the possible effect of inoculation routes and adjuvant on virus clearance and histochemistry changes in the lungs of mice. The results indicated that intramuscular inoculation is a more effective and antigen dose-sparing route to enhance the immune response, although subcutaneous inoculation induced faster and stronger IgG antibodies after the initial immunization. Furthermore, adjuvant, but not immunization route, is a more critical factor to affect the humoral/cellular immune response and the immune bias. In addition, adjuvant inoculated via the intramuscular route is safer than that via the subcutaneous route, especially for AS02. This study highlights the importance of the adjuvant and immunization routes in the design and clinical transformation of adjuvanted vaccines. Further investigation is needed to illustrate the mechanism underlying the above difference in both efficiency and safety.
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spelling doaj.art-cd6af0f723d8447fbf457ea7546ca6c02022-12-22T03:03:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.938598938598Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c MiceLijun Bian0Yu Zheng1Xiaohong Guo2Dongdong Li3Jingying Zhou4Linyao Jing5Yan Chen6Yan Chen7Yan Chen8Jingcai Lu9Ke Zhang10Chunlai Jiang11Chunlai Jiang12Chunlai Jiang13Chunlai Jiang14Yong Zhang15Yong Zhang16Yong Zhang17Wei Kong18Wei Kong19Wei Kong20Wei Kong21National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaKey Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, ChinaNMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, ChinaR&D Center, Changchun BCHT Biotechnology Co., Changchun, ChinaThe Key and Characteristic Laboratory of Modern Pathogen Biology, Department of Parasitology, Basic Medical College, Guizhou Medical University, Guiyang, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaKey Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, ChinaNMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, ChinaR&D Center, Changchun BCHT Biotechnology Co., Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaKey Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, ChinaNMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, ChinaKey Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Changchun, ChinaNMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, ChinaR&D Center, Changchun BCHT Biotechnology Co., Changchun, ChinaWe previously explored a panel of adjuvants formulated with pre-fusion RSV-F protein and found that AS02 may be a promising candidate adjuvant for developing RSV-F subunit vaccines with improved immunogenicity and desired immune response type. In this study, we performed a head-to-head comparison of the effect of intramuscular injection to that of subcutaneous injection on the immune response and protective efficacy of recombinant RSV-F subunit vaccine with or without adjuvants (Alhydrogel, squalene-based emulsion adjuvants MF59, AS03, and AS02) in BALB/c mice. After inoculations, antigen-specific antibodies, neutralizing antibodies, antibody subtypes, cytokines, and the persistence of immune response were evaluated. Moreover, challenge tests were also performed to illustrate the possible effect of inoculation routes and adjuvant on virus clearance and histochemistry changes in the lungs of mice. The results indicated that intramuscular inoculation is a more effective and antigen dose-sparing route to enhance the immune response, although subcutaneous inoculation induced faster and stronger IgG antibodies after the initial immunization. Furthermore, adjuvant, but not immunization route, is a more critical factor to affect the humoral/cellular immune response and the immune bias. In addition, adjuvant inoculated via the intramuscular route is safer than that via the subcutaneous route, especially for AS02. This study highlights the importance of the adjuvant and immunization routes in the design and clinical transformation of adjuvanted vaccines. Further investigation is needed to illustrate the mechanism underlying the above difference in both efficiency and safety.https://www.frontiersin.org/articles/10.3389/fimmu.2022.938598/fullrespiratory syncytial virussubunit vaccinevaccine adjuvantinoculation routeadministration route
spellingShingle Lijun Bian
Yu Zheng
Xiaohong Guo
Dongdong Li
Jingying Zhou
Linyao Jing
Yan Chen
Yan Chen
Yan Chen
Jingcai Lu
Ke Zhang
Chunlai Jiang
Chunlai Jiang
Chunlai Jiang
Chunlai Jiang
Yong Zhang
Yong Zhang
Yong Zhang
Wei Kong
Wei Kong
Wei Kong
Wei Kong
Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice
Frontiers in Immunology
respiratory syncytial virus
subunit vaccine
vaccine adjuvant
inoculation route
administration route
title Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice
title_full Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice
title_fullStr Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice
title_full_unstemmed Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice
title_short Intramuscular Inoculation of AS02-Adjuvanted Respiratory Syncytial Virus (RSV) F Subunit Vaccine Shows Better Efficiency and Safety Than Subcutaneous Inoculation in BALB/c Mice
title_sort intramuscular inoculation of as02 adjuvanted respiratory syncytial virus rsv f subunit vaccine shows better efficiency and safety than subcutaneous inoculation in balb c mice
topic respiratory syncytial virus
subunit vaccine
vaccine adjuvant
inoculation route
administration route
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.938598/full
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