Poster Presentation 9th Australasian Vaccines & Immunotherapeutics Development Meeting 2022

Resistance of SARS-CoV-2 omicron to potent humoral responses and clinical immunotherapeutics relative to previous variants of concern (#114)

Gregory J Walker 1 2 , Anupriya Aggarwal 1 3 , Alberto Ospina Stella 1 3 , Anouschka Akerman 1 3 , Vanessa Milogiannakis 1 3 , Supavadee Amatayakul-Chantler 4 , Alexandra Carey Hoppe 1 3 , Mee Ling Munier 1 3 , Hans-Martin Jack 5 , David Darley 6 , Gail Matthews 1 3 , Deborah Burnett 7 , Daniel Christ 7 , William Rawlinson 1 2 , Anthony Kelleher 1 3 , Stuart Turville 1 3
  1. UNSW, Sydney, NSW, Australia
  2. Serology and Virology Division, NSW Health Pathology, Randwick, NSW, Australia
  3. Kirby Institute, Sydney, NSW, Australia
  4. CSL Behring, Bern, Switzerland
  5. University of Erlangen-Nurnberg, Erlangen, Germany
  6. St. Vincent's Hospital, Sydney, NSW, Australia
  7. Garvan Institute of Medical Research, Sydney, NSW, Australia

In late 2021, the variant omicron (B.1.1.529) emerged eclipsing the other variants of concern (VOC) in its number of Spike polymorphisms, and its ability to compete with and displace the dominant VOC delta. We assessed the impact of omicron on humoral neutralisation in vaccinated and convalescent cohorts, in concentrated human IgG from thousands of plasma donors, and clinically utilised monoclonal antibodies. Overall, we observed a 17 to 22-fold drop in neutralisation titres across all donors that had a detectable titre to Omicron. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth but its potency was still reduced by 16-fold. Of all therapeutic antibodies tested, significant neutralisation was maintained by Sotrovimab, with other monoclonal antibodies weakly or unable to neutralise B.1.1.529. These findings were pivotal in updating COVID-19 treatment guidelines and directing therapeutic development. The ongoing evaluation of immunotherapeutics will be crucial in combatting the pandemic moving forward, as new SARS-CoV-2 variants inevitably emerge.