ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Mutants strike back: vaccine-induced antibodies against emerging SARS-CoV-2 RBD variants (#275)

Ebene R Haycroft 1 , Ester Lopez 1 , Samantha K Davis 1 , Adam K Wheatley 1 , Jennifer A Juno 1 , Samuel J Redmond 1 , Nicholas A Gherardin 1 , Dale I Godfrey 1 2 , Wai-Hong Tham 3 4 , Kevin J Selva 1 , Stephen J Kent 1 5 6 , Amy W Chung 1
  1. The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia
  2. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Melbourne, VIC, Australia
  3. Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia
  4. The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
  5. Melbourne Sexual Health Centre, Monash University, Melbourne, VIC, Australia
  6. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC, Australia

SARS-CoV-2, the causative agent of the COVID-19 pandemic, remains a formidable challenge to global public health. With the rise of dominant viral variants harbouring mutations in the spike protein, it is critical to understand the impact mutations have on vaccine efficacy. The receptor binding domain (RBD) of the spike is a key target for neutralising antibodies and mutations at this site can generate loss of epitopes for antibodies.

Here, we report antibody binding and neutralisation activity against 44 naturally occurring RBD mutations from plasma of two dose BNT-162b2-vaccine recipients (n = 18) and convalescent SARS-CoV-2-infected individuals with mild/moderate disease (n = 15; median: 38 days). We utilised a high-throughput surrogate neutralisation assay capable of measuring antibody binding characteristics and neutralisation activity against multiple RBD variants simultaneously through multiplexing.

We found significantly higher levels of overall IgG binding responses in vaccinee-recipients compared to convalescent individuals across all 44 RBD variants (p < 0.001). In comparison to the ancestor wild type (WT) strain (Median 1/IC50: 716), we also observed reduced neutralisation capacity of vaccine-plasma to several mutations, including the RBD of beta (B.1.351), gamma (P1), eta (B.1.525), kappa (B.1.617.1) and iota (B.1.526) (Median 1/IC50: 257, 238, 554, 674, 338 respectively). To a slightly lesser extent, we also observed a decrease in the neutralisation capacity of vaccine-plasma against delta (B.1.617.2) (Median 1/IC50: 572) compared to wild type. Our assay also identified single point mutations, such as N501T (Median 1/IC50: 512), that confer reduced neutralisation sensitivity to vaccine-plasma. Collectively, this data highlights various naturally emerged RBD mutations resist neutralisation by BNT-162b2 vaccinated-induced plasma. Understanding immune escape by SARS-CoV-2 is critical for public health, with the potential of viral variants to cause break-through infections by undermining vaccine-induced immunity.