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Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 induction is ideal for influenza

Authors :
Mayumi Sasada
Hironori Hatanaka
Marumi Ohno
Lorena E. Brown
Hiroshi Kida
Yuki Ohara
Daisuke Fujikura
Hiroki Kitayama
Masafumi Endo
Naoki Nomura
Tomio Ikeda
Masashi Shingai
Tomohiro Nishimura
Kazumasa Ogasawara
Tomoyoshi Sobue
Kenji Motokawa
Yoichiro Kino
Takuji Daito
Edin J Mifsud
Saori Suzuki
Yasushi Itoh
Ryotarou Mitsumata
Toshiki Sekiya
Source :
Vaccine. 37:2158-2166
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

In contrast to current ether- or detergent-disrupted "split" vaccines (SVs) for influenza, inactivated whole influenza virus particle vaccines (WPVs) retain the original virus structure and components and as such may confer similar immunity to natural infection. In a collaboration between academia and industry, the potential of WPV as a new seasonal influenza vaccine was investigated. Each of the four seasonal influenza vaccine manufacturers in Japan prepared WPVs and SVs from the same batches of purified influenza virus. Both mice and monkeys vaccinated with the WPVs exhibited superior immune responses to those vaccinated with the corresponding SVs. Vaccination with A/California/07/2009 (H1N1) WPV enabled mice to survive a lethal challenge dose of homologous virus whereas those vaccinated with SV succumbed to infection within 6 days. Furthermore, mice vaccinated with WPV induced substantial numbers of multifunctional CD8+ T cells, important for control of antigenically drifted influenza virus strains. In addition, cytokines and chemokines were detected at early time points in the sera of mice vaccinated with WPV but not in those animals vaccinated with SV. These results indicate that WPVs induce enhanced innate and adaptive immune responses compared to equivalent doses of SVs. Notably, WPV at one fifth of the dose of SV was able to induce potent immunity with limited production of IL-6, one of the pyrogenic cytokines. We thus propose that WPVs with balanced immunogenicity and safety may set a new global standard for seasonal influenza vaccines.

Details

ISSN :
0264410X
Volume :
37
Database :
OpenAIRE
Journal :
Vaccine
Accession number :
edsair.doi.dedup.....b4c81049c83b595e3093f645381468e6