Heterosubtypic Neutralizing Monoclonal Antibodies Cross-Protective against H5N1 and H1N1 Recovered from Human IgM+ Memory B Cells

Background: The hemagglutinin (HA) glycoprotein is the principal target of protective humoral immune responses to influenza virus infections but such antibody responses only provide efficient protection against a narrow spectrum of HA antigenic variants within a given virus subtype. Avian influenza viruses such as H5N1 are currently panzootic and pose a pandemic threat. These viruses are antigenically diverse and protective strategies need to cross protect against diverse viral clades. Furthermore, there are 16 different HA subtypes and no certainty the next pandemic will be caused by an H5 subtype, thus it is important to develop prophylactic and therapeutic interventions that provide heterosubtypic protection. Methods and Findings: Here we describe a panel of 13 monoclonal antibodies (mAbs) recovered from combinatorial display libraries that were constructed from human IgM+ memory B cells of recent (seasonal) influenza vaccinees. The mAbs have broad heterosubtypic neutralizing activity against antigenically diverse H1, H2, H5, H6, H8 and H9 influenza subtypes. Restriction to variable heavy chain gene IGHV1-69 in the high affinity mAb panel was associated with binding to a conserved hydrophobic pocket in the stem domain of HA. The most potent antibody (CR6261) was protective in mice when given before and after lethal H5N1 or H1N1 challenge. Conclusions: The human monoclonal CR6261 described in this study could be developed for use as a broad spectrum agent for prophylaxis or treatment of human or avian influenza infections without prior strain characterization. Moreover, the CR6261 epitope could be applied in targeted vaccine strategies or in the design of novel antivirals. Finally our approach of screening the IgM+ memory repertoire could be applied to identify conserved and functionally relevant targets on other rapidly evolving pathogens

Sunflower and climate change: Possibilities of adaptation through breeding and genomic selection

Due to its ability to grow in different agroecological conditions and its moderate drought tolerance, sunflower may become the oil crop of preference in the future, especially in the light of global environmental changes. In the field conditions, sunflower crop is often simultaneously challenged by different biotic and abiotic stresses, and understanding the shared mechanisms contributing to two or more stresses occurring individually or simultaneously is important to improve crop productivity under foreseeable complex stress situations. Exploitation of the available plant genetic resources in combination with the use of modern molecular tools for genome-wide association studies (GWAS) and application of genomic selection (GS) could lead to considerable improvements in sunflower, especially with regard to different stresses and better adaptation to the climate change. In this chapter we present a review of climate-smart (CS) traits and respective genetic resources and tools for their introduction into the cultivated sunflower, thus making it the oil crop resilient to the extreme climatic conditions and well-known and emerging pests and diseases. © Springer Nature Switzerland AG 2019