Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges

Abstract We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) vaccination induces protective immunity. Our...

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Autores principales: Andrew Chak-Yiu Lee, Anna Jinxia Zhang, Can Li, Yanxia Chen, Feifei Liu, Yan Zhao, Hin Chu, Carol Ho-Yan Fong, Pui Wang, Siu-Ying Lau, Kelvin Kai-Wang To, Honglin Chen, Kwok-Yung Yuen
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:946e30f2e6784f7385e92b341a9850252021-12-02T18:49:16ZIntradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges10.1038/s41541-021-00359-82059-0105https://doaj.org/article/946e30f2e6784f7385e92b341a9850252021-08-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00359-8https://doaj.org/toc/2059-0105Abstract We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) vaccination induces protective immunity. Our results showed that DelNS1-LAIV intradermal vaccination conferred effective and long-lasting protection against lethal virus challenge in mice. A single intradermal injection of DelNS1-LAIV conferred 100% survival with no weight loss in mice after A(H1N1)09 influenza virus (H1N1/415742Md) challenge. DelNS1-LAIV injection resulted in a significant reduction of lung viral load and reduced airway epithelial cell death and lung inflammatory cytokine responses at day 2 and 4 post challenge. Full protections of mice lasted for 6 months after immunization. In vitro infection of DelNS1-LAIV in monocyte-derived dendritic cells (MoDCs) demonstrated activation of antigen-presenting cells at 33 °C, together with the results of abortive replication of DelNS1-LAIV in skin tissue and strong upregulation of inflammatory cytokines/chemokines expression, our results suggested the strong immunogenicity of this vaccine. Further, we demonstrate that the underlying protection mechanism induced by intradermal DelNS1-LAIV is mainly attributed to antibody responses. Together, this study opens up an alternative route for the administration of LAIV, which may benefit individuals not suitable for intranasal LAIV immunization.Andrew Chak-Yiu LeeAnna Jinxia ZhangCan LiYanxia ChenFeifei LiuYan ZhaoHin ChuCarol Ho-Yan FongPui WangSiu-Ying LauKelvin Kai-Wang ToHonglin ChenKwok-Yung YuenNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Andrew Chak-Yiu Lee
Anna Jinxia Zhang
Can Li
Yanxia Chen
Feifei Liu
Yan Zhao
Hin Chu
Carol Ho-Yan Fong
Pui Wang
Siu-Ying Lau
Kelvin Kai-Wang To
Honglin Chen
Kwok-Yung Yuen
Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges
description Abstract We previously developed a temperature-sensitive, and NS1 gene deleted live attenuated influenza vaccine (DelNS1-LAIV) and demonstrated its potent protective efficacy in intranasally vaccinated mice. Here we investigated whether intradermal (i.d.) vaccination induces protective immunity. Our results showed that DelNS1-LAIV intradermal vaccination conferred effective and long-lasting protection against lethal virus challenge in mice. A single intradermal injection of DelNS1-LAIV conferred 100% survival with no weight loss in mice after A(H1N1)09 influenza virus (H1N1/415742Md) challenge. DelNS1-LAIV injection resulted in a significant reduction of lung viral load and reduced airway epithelial cell death and lung inflammatory cytokine responses at day 2 and 4 post challenge. Full protections of mice lasted for 6 months after immunization. In vitro infection of DelNS1-LAIV in monocyte-derived dendritic cells (MoDCs) demonstrated activation of antigen-presenting cells at 33 °C, together with the results of abortive replication of DelNS1-LAIV in skin tissue and strong upregulation of inflammatory cytokines/chemokines expression, our results suggested the strong immunogenicity of this vaccine. Further, we demonstrate that the underlying protection mechanism induced by intradermal DelNS1-LAIV is mainly attributed to antibody responses. Together, this study opens up an alternative route for the administration of LAIV, which may benefit individuals not suitable for intranasal LAIV immunization.
format article
author Andrew Chak-Yiu Lee
Anna Jinxia Zhang
Can Li
Yanxia Chen
Feifei Liu
Yan Zhao
Hin Chu
Carol Ho-Yan Fong
Pui Wang
Siu-Ying Lau
Kelvin Kai-Wang To
Honglin Chen
Kwok-Yung Yuen
author_facet Andrew Chak-Yiu Lee
Anna Jinxia Zhang
Can Li
Yanxia Chen
Feifei Liu
Yan Zhao
Hin Chu
Carol Ho-Yan Fong
Pui Wang
Siu-Ying Lau
Kelvin Kai-Wang To
Honglin Chen
Kwok-Yung Yuen
author_sort Andrew Chak-Yiu Lee
title Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges
title_short Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges
title_full Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges
title_fullStr Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges
title_full_unstemmed Intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges
title_sort intradermal vaccination of live attenuated influenza vaccine protects mice against homologous and heterologous influenza challenges
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/946e30f2e6784f7385e92b341a985025
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