A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice

ABSTRACT High-intensity focused ultrasound (HIFU), a noninvasive ablation therapy that has been widely used clinically in ablation of solid tumors, induces immune sensitization. We therefore in this study investigated whether HIFU treatment could enhance the efficacy of a herpes simplex virus 2 (HSV...

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Autores principales: Juhua Xiao, Xin Zhou, Ye Luo, Shuang Wang, Zhili Yang, Yingchun Yi, Hui Xiong
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:c37242a33f8c4260af9ad0aab45664342021-11-15T15:31:12ZA Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice10.1128/mSphere.00859-202379-5042https://doaj.org/article/c37242a33f8c4260af9ad0aab45664342020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00859-20https://doaj.org/toc/2379-5042ABSTRACT High-intensity focused ultrasound (HIFU), a noninvasive ablation therapy that has been widely used clinically in ablation of solid tumors, induces immune sensitization. We therefore in this study investigated whether HIFU treatment could enhance the efficacy of a herpes simplex virus 2 (HSV-2) vaccine. First, we observed that in HSV-2-positive cervical intraepithelial neoplasia (CIN) II patients, HIFU treatment induced significantly higher anti-HSV-2 neutralization response than surgical removal. Next, we tested the efficacy of HIFU-treated, UV-inactivated HSV-2-infected cells as a proof-of-concept vaccine in mice. Our data showed that HIFU-treated formulation significantly enhanced HSV-2 antibody titers and neutralization titers, compared to UV-, microwave (MW)-, or freeze-thaw (FT)-treated formulations. HIFU treatment also promoted the Th1/2 cell-mediated response. A long-term full protection was observed in mice that received the HIFU-treated formulation, and no weight loss was detected. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy. IMPORTANCE High-intensity focused ultrasound (HIFU) is mainly used in tumor ablation and tumor vaccinology study. It has been shown to induce immune sensitization and enhance tumor responsiveness to other therapies. Our study has shown enhanced anti-HSV-2 response in HIFU-treated CIN II patients. Furthermore, in a murine model, we have demonstrated that HIFU-treated HSV-2 vaccine induced long-term protective immunity against lethal challenge. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.Juhua XiaoXin ZhouYe LuoShuang WangZhili YangYingchun YiHui XiongAmerican Society for Microbiologyarticleherpes simplex virus 2high-intensity focused ultrasoundlong-term immunityvaccine efficacyMicrobiologyQR1-502ENmSphere, Vol 5, Iss 6 (2020)
institution DOAJ
collection DOAJ
language EN
topic herpes simplex virus 2
high-intensity focused ultrasound
long-term immunity
vaccine efficacy
Microbiology
QR1-502
spellingShingle herpes simplex virus 2
high-intensity focused ultrasound
long-term immunity
vaccine efficacy
Microbiology
QR1-502
Juhua Xiao
Xin Zhou
Ye Luo
Shuang Wang
Zhili Yang
Yingchun Yi
Hui Xiong
A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice
description ABSTRACT High-intensity focused ultrasound (HIFU), a noninvasive ablation therapy that has been widely used clinically in ablation of solid tumors, induces immune sensitization. We therefore in this study investigated whether HIFU treatment could enhance the efficacy of a herpes simplex virus 2 (HSV-2) vaccine. First, we observed that in HSV-2-positive cervical intraepithelial neoplasia (CIN) II patients, HIFU treatment induced significantly higher anti-HSV-2 neutralization response than surgical removal. Next, we tested the efficacy of HIFU-treated, UV-inactivated HSV-2-infected cells as a proof-of-concept vaccine in mice. Our data showed that HIFU-treated formulation significantly enhanced HSV-2 antibody titers and neutralization titers, compared to UV-, microwave (MW)-, or freeze-thaw (FT)-treated formulations. HIFU treatment also promoted the Th1/2 cell-mediated response. A long-term full protection was observed in mice that received the HIFU-treated formulation, and no weight loss was detected. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy. IMPORTANCE High-intensity focused ultrasound (HIFU) is mainly used in tumor ablation and tumor vaccinology study. It has been shown to induce immune sensitization and enhance tumor responsiveness to other therapies. Our study has shown enhanced anti-HSV-2 response in HIFU-treated CIN II patients. Furthermore, in a murine model, we have demonstrated that HIFU-treated HSV-2 vaccine induced long-term protective immunity against lethal challenge. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.
format article
author Juhua Xiao
Xin Zhou
Ye Luo
Shuang Wang
Zhili Yang
Yingchun Yi
Hui Xiong
author_facet Juhua Xiao
Xin Zhou
Ye Luo
Shuang Wang
Zhili Yang
Yingchun Yi
Hui Xiong
author_sort Juhua Xiao
title A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice
title_short A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice
title_full A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice
title_fullStr A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice
title_full_unstemmed A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice
title_sort novel high-intensity focused ultrasound-treated herpes simplex virus 2 vaccine induces long-term protective immunity against lethal challenge in mice
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/c37242a33f8c4260af9ad0aab4566434
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