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- E. Snelders (Netherlands)
Dermatophytes in India
- A. Chowdhary (India)
The Successful Global Spread of Azole Resistance in Aspergillus Fumigatus; Accidental or Inevitable?
- E. Snelders (Netherlands)
Abstract
Abstract Body
The case of resistance development in the common saprobic fungus Aspergillus fumigatus to agricultural fungicides and its cross-resistance to medical azoles is causing alarming mortality in vulnerable patient-groups. A crucial piece of evidence that supports the environment-to-patient route is the observation that azole-resistant strains collected from the environment share identical resistance mechanisms with those collected from patients. Only two main resistant haplotypes are dominant in the Dutch Aspergillus fumigatus population leading to the question whether this is an accidental or rare event, that has been able to increase in prevalence, or whether azole cross-restance development is inevitable, due to the widespread environmental of azoles.
Antiviral Drug Resistance and Immune Evasion
- A. J. Greaney (United States of America)
Abstract
Abstract Body
The SARS-CoV-2 spike receptor binding domain (RBD) is a major target of neutralizing antibodies, but the emergence of viral variants with mutations in key antibody epitopes has raised concerns that antigenic evolution could erode adaptive immunity elicited by prior infection or vaccination. The antigenic consequences of viral mutations are not always clear due to the lag time between the identification and in vitro characterization of a new viral variant of interest. Thus, we developed a prospective approach to characterize all possible mutations to the RBD, even before they are detected in sequenced viral isolates. We used a yeast-display deep mutational scanning system to measure how all possible mutations to the RBD affect antibody binding. We applied this approach to comprehensively map mutations that escape binding by therapeutic monoclonal antibodies and polyclonal antibodies from individuals who had been vaccinated against SARS-CoV-2 or infected with different viral variants (early 2020, Beta variant, or Delta variant viruses). We also determined how the neutralizing antibody response in these individuals were affected by key mutations to the RBD. We found that different infection and vaccination histories lead to polyclonal antibody specificities that are differentially affected by viral mutations. These results indicate that individuals with different immune histories may have a differing susceptibility to erosion of antibody immunity by SARS-CoV-2 evolution.