4.4 Article

Development of a universal influenza vaccine using hemagglutinin stem protein produced from Pichia pastoris

Journal

VIROLOGY
Volume 526, Issue -, Pages 125-137

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2018.10.005

Keywords

Influenza vaccine; Hemagglutinin stem; Pichia pastoris; Fermentation

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Funding

  1. Academia Sinica
  2. Ministry of Science and Technology [MOST 106-0210-01-15-02, MOST 107-0210-01-19-01]

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The development of a universal influenza vaccine has become a major effort to combat the high mutation rate of influenza. To explore the use of the highly conserved stem region of hemagglutinin (HA) as a universal vaccine, we produced HA-stem-based protein using yeast expression systems. The glycosylation effects on the immunogenicity and protection activities were investigated. The yield of the A/Brisbane/59/2007 HA stem produced from Pichia pastoris reached 100 mg/l. The immunogenicity of HA stem proteins in various glycoforms was further investigated and compared. All glycoforms of the HA stem protein can induce cross-reactive antibody responses, antibody-dependent cellular cytotoxicity (ADCC)-mediated protection as well as T-cell responses, with broad protection in mice. The monoglycosylated form of the A/Brisbane/59/2007 HA stem produced in yeast, together with the glycolipid C34 as the adjuvant, can elicit greater ADCC responses, better neutralizing activities against heterologous strains, and broader protection in mice.

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