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Virology. 2018 Oct 26;526:125-137. doi: 10.1016/j.virol.2018.10.005. [Epub ahead of print]
Development of a universal influenza vaccine using hemagglutinin stem protein produced from Pichia pastoris.
Wang SC1, Liao HY2, Zhang JY2, Cheng TR3, Wong CH4.
Author information
Abstract
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.
KEYWORDS:
Fermentation; Hemagglutinin stem; Influenza vaccine; Pichia pastoris
PMID: 30388628 DOI: 10.1016/j.virol.2018.10.005
Development of a universal influenza vaccine using hemagglutinin stem protein produced from Pichia pastoris.
Wang SC1, Liao HY2, Zhang JY2, Cheng TR3, Wong CH4.
Author information
Abstract
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.
KEYWORDS:
Fermentation; Hemagglutinin stem; Influenza vaccine; Pichia pastoris
PMID: 30388628 DOI: 10.1016/j.virol.2018.10.005