Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses.

Published

Journal Article

Virus-like particles (VLPs) provide a well-established vaccine platform; however, the immunogenic properties acquired by VLP structure remain poorly understood. In this study, we showed that systemic vaccination with norovirus VLP recalls human IgA responses at higher magnitudes than IgG responses under a humanized mouse model that was established by introducing human PBMCs in severely immunodeficient mice. The recall responses elicited by VLP vaccines depended on VLP structure and the disruption of VLP attenuated recall responses, with a more profound reduction being observed in IgA responses. The IgA-focusing property was also conserved in a murine norovirus-primed model under which murine IgA responses were recalled in a manner dependent on VLP structure. Importantly, the VLP-driven IgA response preferentially targeted virus-neutralizing epitopes located in the receptor-binding domain. Consequently, VLP-driven IgA responses were qualitatively superior to IgG responses in terms of the virus-neutralizing activity in vitro. Furthermore, the IgA in mucosa obtained remarkable protective function toward orally administrated virus in vivo. Thus, our results indicate the immune-focusing properties of the VLP vaccine that improve the quality/quantity of mucosal IgA responses, a finding with important implications for developing mucosal vaccines.

Full Text

Duke Authors

Cited Authors

  • Onodera, T; Hashi, K; Shukla, RK; Miki, M; Takai-Todaka, R; Fujimoto, A; Kuraoka, M; Miyoshi, T; Kobayashi, K; Hasegawa, H; Ato, M; Kelsoe, G; Katayama, K; Takahashi, Y

Published Date

  • December 15, 2019

Published In

Volume / Issue

  • 203 / 12

Start / End Page

  • 3282 - 3292

PubMed ID

  • 31704880

Pubmed Central ID

  • 31704880

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1900481

Language

  • eng

Conference Location

  • United States