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

Publication ,  Journal Article
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 ...
Published in: J Immunol
December 15, 2019

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.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2019

Volume

203

Issue

12

Start / End Page

3282 / 3292

Location

United States

Related Subject Headings

  • Vaccines, Virus-Like Particle
  • Norovirus
  • Mice, Transgenic
  • Mice
  • Immunology
  • Immunologic Memory
  • Immunoglobulin G
  • Immunoglobulin Class Switching
  • Immunoglobulin A
  • Immunity, Mucosal
 

Citation

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Onodera, T., Hashi, K., Shukla, R. K., Miki, M., Takai-Todaka, R., Fujimoto, A., … Takahashi, Y. (2019). Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses. J Immunol, 203(12), 3282–3292. https://doi.org/10.4049/jimmunol.1900481
Onodera, Taishi, Kana Hashi, Rajni Kant Shukla, Motohiro Miki, Reiko Takai-Todaka, Akira Fujimoto, Masayuki Kuraoka, et al. “Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses.J Immunol 203, no. 12 (December 15, 2019): 3282–92. https://doi.org/10.4049/jimmunol.1900481.
Onodera T, Hashi K, Shukla RK, Miki M, Takai-Todaka R, Fujimoto A, et al. Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses. J Immunol. 2019 Dec 15;203(12):3282–92.
Onodera, Taishi, et al. “Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses.J Immunol, vol. 203, no. 12, Dec. 2019, pp. 3282–92. Pubmed, doi:10.4049/jimmunol.1900481.
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. Immune-Focusing Properties of Virus-like Particles Improve Protective IgA Responses. J Immunol. 2019 Dec 15;203(12):3282–3292.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2019

Volume

203

Issue

12

Start / End Page

3282 / 3292

Location

United States

Related Subject Headings

  • Vaccines, Virus-Like Particle
  • Norovirus
  • Mice, Transgenic
  • Mice
  • Immunology
  • Immunologic Memory
  • Immunoglobulin G
  • Immunoglobulin Class Switching
  • Immunoglobulin A
  • Immunity, Mucosal