An avian influenza H5N1 virus vaccine candidate based on the extracellular domain produced in yeast system as subviral particles protects chickens from lethal challenge

Abstract

Highly pathogenic avian influenza is an on-going problem in poultry and a potential human pandemic threat. Pandemics occur suddenly and vaccine production must be fast and effective to be of value in controlling the spread of the virus. In this study we evaluated the potential of a recombinant protein from the extracellular domain of an H5 hemagglutinin protein produced in a yeast expression system to act as an effective vaccine. Protein production was efficient, with up to 200 mg purified from 1 L of culture medium. We showed that the deletion of the multibasic cleavage site from the protein improves oligomerization and, consequentially, its immunogenicity. We also showed that immunization with this deleted protein protected chickens from challenge with a highly pathogenic avian influenza H5N1 virus. Our results suggest that this recombinant protein produced in yeast may be an effective vaccine against H5N1 virus in poultry.

The Length of N-Glycans of Recombinant H5N1 Hemagglutinin Influences the Oligomerization and Immunogenicity of Vaccine Antigen

“…The vaccine based on this HA domain fully protected chickens from lethal infections by the highly pathogenic H5N1 virus (22). This time, in order to obtain the antigens with a native protein sequence, we excluded any affinity tags.…”

“…It was reported that all human cells use this glycan moiety as a foundation to form complex glycans (21). Previously, we showed that immunization with the subunit vaccine based on the extracellular region of H5 hemagglutinin with deletion of the multibasic cleavage site fully protected chickens from lethal infections by the highly pathogenic H5N1 virus (22). We also demonstrated that such an antigen spontaneously oligomerized into spherical structures.…”

High-Titre Neutralizing Antibodies to H1N1 Influenza Virus after Mouse Immunization with Yeast Expressed H1 Antigen: A Promising Influenza Vaccine Candidate

“…Our previous results showed that the recombinant H5 protein encompassing residues from the extracellular domain adopted the correct three-dimensional structure required for oligomerization. Moreover, the H5 vaccine produced in Pichia cells proved to be protective for chickens challenged with a lethal dose of the highly pathogenic H5N1 virus [9]. Therefore, in this study, the transmembrane region and cytoplasmic tail of the H1 protein were also excluded.…”

“…The aim of this study was to test an H1N1pdm09 influenza virus HA produced in a yeast expression system as a potential vaccine antigen. Our previous study showed that the H5 antigen produced in the P. pastoris cells is capable of inducing a specific immune response in mice [8, 10] and providing full protection in chicken [9]. Ease of preparation, low cost of production, and high immunogenicity of the yeast-derived antigen prompted us to test an H1N1pdm09 influenza virus antigen.…”

Dynamic Propagation and Impact of Pandemic Influenza A (2009 H1N1) in Children: A Detailed Review

“…In 2014, two novel lines of influenza A virus H17N10 and H18N11 subtypes were detected in rectal swabs of the small yellow-shouldered bat and the flat-faced fruit-eating bat [ 46 ]. To date, only glycoprotein’s subtypes N1, N2 and H1, H2, H3 are known to have positively adapted to humans [ 47 ].…”