Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory illness, particularly in infants, the elderly, and immunocompromised adults. There is no licensed commercial vaccine against RSV. Importantly, formalin-inactivated RSV vaccines mediate enhanced respiratory disease. RSV fusion...
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Frontiers Media S.A.
2020-09-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.526965/full |
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doaj-390004ed5fa247bab5a2b06ba96546be |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Zheng Lijun Bian Huiting Zhao Yulan Liu Jingcai Lu Jingcai Lu Dawei Liu Dawei Liu Ke Zhang Yueshuang Song Yueshuang Song Yusi Luo Chunlai Jiang Chunlai Jiang Yan Chen Yan Chen Yong Zhang Yong Zhang Wei Kong Wei Kong |
spellingShingle |
Yu Zheng Lijun Bian Huiting Zhao Yulan Liu Jingcai Lu Jingcai Lu Dawei Liu Dawei Liu Ke Zhang Yueshuang Song Yueshuang Song Yusi Luo Chunlai Jiang Chunlai Jiang Yan Chen Yan Chen Yong Zhang Yong Zhang Wei Kong Wei Kong Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice Frontiers in Immunology respiratory syncytial virus subunit vaccine vaccine adjuvant humoral immunity cellular immunity |
author_facet |
Yu Zheng Lijun Bian Huiting Zhao Yulan Liu Jingcai Lu Jingcai Lu Dawei Liu Dawei Liu Ke Zhang Yueshuang Song Yueshuang Song Yusi Luo Chunlai Jiang Chunlai Jiang Yan Chen Yan Chen Yong Zhang Yong Zhang Wei Kong Wei Kong |
author_sort |
Yu Zheng |
title |
Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice |
title_short |
Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice |
title_full |
Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice |
title_fullStr |
Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice |
title_full_unstemmed |
Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice |
title_sort |
respiratory syncytial virus f subunit vaccine with as02 adjuvant elicits balanced, robust humoral and cellular immunity in balb/c mice |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-09-01 |
description |
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory illness, particularly in infants, the elderly, and immunocompromised adults. There is no licensed commercial vaccine against RSV. Importantly, formalin-inactivated RSV vaccines mediate enhanced respiratory disease. RSV fusion (F) protein with pre-fusion conformation is a promising candidate subunit vaccine. However, some problems remain to be solved, such as low immunogenicity and humoral immunity bias. Adjuvants can effectively enhance and adjust vaccine immune responses. In this study, we formulated pre-fusion RSV-F protein with the adjuvants, Alhydrogel, MF59, AS03, AS02, and glycol chitosan (GCS). We then conducted head-to-head comparisons of vaccine-induced immune responses in BALB/c mice. All adjuvanted vaccines enhanced antigen-specific and neutralizing antibody titers and viral clearance and gave an order of adjuvant activity: AS02 > AS03, MF59 > GCS, and Alhydrogel. Among them, AS02 elicited the highest antibody expression, which persisted until week 18. Moreover, AS02 significantly enhanced Th1 type immune response in immunized mice. Mice in the AS02 group also showed faster recovery from viral attacks in challenge tests. Further transcriptome analysis revealed that AS02 regulates immune balance by activating TLR-4 and promotes Th1-type immune responses. These results suggest that AS02 may be an excellent candidate adjuvant for RSV-F subunit vaccines. This study also provides valuable information regarding the effect of other adjuvants on immune responses of RSV-F subunit vaccines. |
topic |
respiratory syncytial virus subunit vaccine vaccine adjuvant humoral immunity cellular immunity |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.526965/full |
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doaj-390004ed5fa247bab5a2b06ba96546be2020-11-25T03:48:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.526965526965Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c MiceYu Zheng0Lijun Bian1Huiting Zhao2Yulan Liu3Jingcai Lu4Jingcai Lu5Dawei Liu6Dawei Liu7Ke Zhang8Yueshuang Song9Yueshuang Song10Yusi Luo11Chunlai Jiang12Chunlai Jiang13Yan Chen14Yan Chen15Yong Zhang16Yong Zhang17Wei Kong18Wei Kong19National 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, ChinaR&D Center, Changchun BCHT Biotechnology Co., Changchun, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Sciences, 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, ChinaR&D Center, Changchun BCHT Biotechnology Co., Changchun, ChinaIntensive Care Unit, Department of Emergency, Guizhou Medical University Affiliated Hospital, 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, 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, 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, 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, ChinaRespiratory syncytial virus (RSV) is a leading cause of lower respiratory illness, particularly in infants, the elderly, and immunocompromised adults. There is no licensed commercial vaccine against RSV. Importantly, formalin-inactivated RSV vaccines mediate enhanced respiratory disease. RSV fusion (F) protein with pre-fusion conformation is a promising candidate subunit vaccine. However, some problems remain to be solved, such as low immunogenicity and humoral immunity bias. Adjuvants can effectively enhance and adjust vaccine immune responses. In this study, we formulated pre-fusion RSV-F protein with the adjuvants, Alhydrogel, MF59, AS03, AS02, and glycol chitosan (GCS). We then conducted head-to-head comparisons of vaccine-induced immune responses in BALB/c mice. All adjuvanted vaccines enhanced antigen-specific and neutralizing antibody titers and viral clearance and gave an order of adjuvant activity: AS02 > AS03, MF59 > GCS, and Alhydrogel. Among them, AS02 elicited the highest antibody expression, which persisted until week 18. Moreover, AS02 significantly enhanced Th1 type immune response in immunized mice. Mice in the AS02 group also showed faster recovery from viral attacks in challenge tests. Further transcriptome analysis revealed that AS02 regulates immune balance by activating TLR-4 and promotes Th1-type immune responses. These results suggest that AS02 may be an excellent candidate adjuvant for RSV-F subunit vaccines. This study also provides valuable information regarding the effect of other adjuvants on immune responses of RSV-F subunit vaccines.https://www.frontiersin.org/article/10.3389/fimmu.2020.526965/fullrespiratory syncytial virussubunit vaccinevaccine adjuvanthumoral immunitycellular immunity |