Inger Heldal
Lead Engineer
Authors
Iuliana Caras Irina-Elena Ionescu Ana-Maria Pantazica Andre van Eerde Hege Særvold Steen Inger Heldal Sissel Haugslien Catalin Tucureanu Raluca-Elena Chelmus Vlad-Constantin Tofan Adriana Costache Adrian Onu Hang Su Norica Branza-Nichita Jihong Liu Clarke Crina StavaruAbstract
No abstract has been registered
Authors
Ana-Maria Madalina Pantazica Andre van Eerde Mihaela-Olivia Dobrica Iuliana Caras Irina Ionescu Adriana Costache Catalin Tucureanu Hege Særvold Steen Catalin Lazar Inger Heldal Sissel Haugslien Adrian Onu Crina Stavaru Norica Branza-Nichita Jihong Liu ClarkeAbstract
The recent SARS-CoV-2 pandemic has taught the world a costly lesson about the devastating consequences of viral disease outbreaks but also, the remarkable impact of vaccination in limiting life and economic losses. Vaccination against human Hepatitis B Virus (HBV), a major human pathogen affecting 290 million people worldwide, remains a key action towards viral hepatitis elimination by 2030. To meet this goal, the development of improved HBV antigens is critical to overcome non-responsiveness to standard vaccines based on the yeast-produced, small (S) envelope protein. We have recently shown that combining relevant immunogenic determinants of S and large (L) HBV proteins in chimeric antigens markedly enhances the anti-HBV immune response. However, the demand for cost-efficient, high-quality antigens remains challenging. This issue could be addressed by using plants as versatile and rapidly scalable protein production platforms. Moreover, the recent generation of plants lacking β-1,2-xylosyltransferase and α-1,3-fucosyltransferase activities (FX-KO), by CRISPR/Cas9 genome editing, enables production of proteins with “humanized” N-glycosylation. In this study, we investigated the impact of plant N-glycosylation on the immunogenic properties of a chimeric HBV S/L vaccine candidate produced in wild-type and FX-KO Nicotiana benthamiana. Prevention of β-1,2-xylose and α-1,3-fucose attachment to the HBV antigen significantly increased the immune response in mice, as compared with the wild-type plant-produced counterpart. Notably, the antibodies triggered by the FX-KO-made antigen neutralized more efficiently both wild-type HBV and a clinically relevant vaccine escape mutant. Our study validates in premiere the glyco-engineered Nicotiana benthamiana as a substantially improved host for plant production of glycoprotein vaccines.
Authors
Nina Elisabeth Nagy Hans Ragnar Norli Monica Fongen Runa Berg Østby Inger Heldal Jahn Davik Ari HietalaAbstract
Tree defense against xylem pathogens involves both constitutive and induced phenylpropanoids and terpenoids. The induced defenses include compartmentalization of compromised wood with a reaction zone (RZ) characterized by polyphenol deposition, whereas the role of terpenoids has remained poorly understood. To further elucidate the tree–pathogen interaction, we profiled spatial patterns in lignan (low-molecular-weight polyphenols) and terpenoid content in Norway spruce (Picea abies) trees showing heartwood colonization by the pathogenic white-rot fungus Heterobasidion parviporum. There was pronounced variation in the amount and composition of lignans between different xylem tissue zones of diseased and healthy trees. Intact RZ at basal stem regions, where colonization is the oldest, showed the highest level and diversity of these compounds. The antioxidant properties of lignans obviously hinder oxidative degradation of wood: RZ with lignans removed by extraction showed significantly higher mass loss than unextracted RZ when subjected to Fenton degradation. The reduced diversity and amount of lignans in pathogen-compromised RZ and decaying heartwood in comparison to intact RZ and healthy heartwood suggest that α-conindendrin isomer is an intermediate metabolite in lignan decomposition by H. parviporum. Diterpenes and diterpene alcohols constituted above 90% of the terpenes detected in sapwood of healthy and diseased trees. A significant finding was that traumatic resin canals, predominated by monoterpenes, were commonly associated with RZ. The findings clarify the roles and fate of lignan during wood decay and raise questions about the potential roles of terpenoids in signal transduction, synthesis, and translocation of defense compounds upon wood compartmentalization against decay fungi.
