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

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

doi:10.1038/s41541-021-00359-8

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

NPJ Vaccines. 2021 Aug 4;6(1):95. doi: 10.1038/s41541-021-00359-8.

Authors

Andrew Chak-Yiu Lee¹, Anna Jinxia Zhang^{1

2

3}, Can Li¹, Yanxia Chen¹, Feifei Liu¹, Yan Zhao¹, Hin Chu¹, Carol Ho-Yan Fong¹, Pui Wang¹, Siu-Ying Lau¹, Kelvin Kai-Wang To^{1

2

3}, Honglin Chen^{1

2

3}, Kwok-Yung Yuen^{4

5

6}

Affiliations

¹ Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
² Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
³ State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
⁴ Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. kyyuen@hku.hk.
⁵ Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China. kyyuen@hku.hk.
⁶ State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China. kyyuen@hku.hk.

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.