Poster Presentation Lorne Infection and Immunity 2023

Robust SARS-CoV-2 T cell immunity towards COVID-19 vaccines in haematology patients of varying malignancies and immunosuppressive treatment (#174)

Oanh Nguyen 1 , Louise Rowntree 1 , Lily Allen 1 , Brendon Chua 1 , Lukasz Kedzierski 1 , Chhay Lim 2 , Masa Lasica 3 , Surekha Tennakoon 2 , Natalie Saunders 2 , Megan Crane 2 , Lynette Chee 2 4 , John Seymour 2 , Mary Anderson 2 , Ashley Whitechurch 2 , Bridie Clemens 1 , Wuji Zhang 1 , So Young Chang 1 , Jennifer Habel 1 , Xiaoxiao Jia 1 , Hayley McQuilten 1 , Anastasia Minervina 5 , Mikhail Pogorelyy 5 , Priyanka Chaurasia 6 , Jan Petersen 6 , Tejas Menon 1 , Luca Hensen 1 , Jessica Neil 1 , Francesca Mordant 1 , Hyon-Xhi Tan 1 , Adam Wheatley 1 , Stephen Kent 1 , Kanta Subbarao 7 , Theo Karapanagiotidis 8 , Suellen Nicholson 8 , Florian Krammer 9 , Grace Gibney 10 , Fiona James 10 , Janine Trevillyan 10 , Jason Trubiano 10 , Jeni Mitchell 4 , Britt Christensen 4 , Katherine Bond 4 , Deborah Williamson 8 , Jamie Rossjohn 6 , Jeremy Chase Crawford 5 , Paul Thomas 5 , Karin Thursky 2 , Monica Slavin 2 , Constantine Tam 2 3 , Benjamin Teh 2 , Katherine Kedzierska 1
  1. University of Melbourne, Melbourne
  2. Peter MacCallum Cancer Centre, Melbourne
  3. St Vincent's Hospital, Melbourne , Fitzroy
  4. Royal Melbourne Hospital, Melbourne
  5. St. Jude Children's Research Hospital, Memphis
  6. Monash University, Clayton
  7. WHO Collaborating Centre for Reference and Research on Influenza, Melbourne
  8. Victorian Infectious Diseases Reference Laboratory, Melbourne
  9. Icahn School of Medicine at Mount Sinai, New York
  10. Austin Health, Heidelberg

Patients undergoing HSCT or CAR-T therapy and CLL patients are heavily immunocompromised and highly vulnerable to severe COVID-19 infection. These patients can respond poorly to vaccination and have perturbed immunity. We evaluated a breadth of immune responses in HSCT, post-CAR-T and CLL patients across three doses of COVID-19 vaccination in comparison to healthy individuals. Presence of seropositive RBD-IgG antibodies were low after 1st dose of BNT162b2 (27%, +3wk) and ChAdOx1 (26%, +12wk) vaccine, which increased to 75% and 59% at 1 month after 2nd dose, respectively. Third mRNA dose increased antibody responses to 85%, demonstrating that a subset of patients still had no antibodies after 3 doses of COVID-19 vaccination. Conversely, complete 100% seropositivity was observed in healthy controls following 1st, 2nd and booster dose with either vaccine. Two doses induced prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) type-1 responses in healthy participants, while haematology patients showed prolonged presence of ASCs and skewed Tfh2/17 responses. Induction of spike-specific memory B-cells correlated with RBD-IgG antibodies, particularly in patients with non-B-cell malignancies. Importantly, vaccine-induced expansions of spike-specific (AIMS/ICS) and peptide-HLA tetramer-specific CD4+/CD8+ T cell responses detected directly ex vivo and their TCR repertoires were robust across all patient disease groups, irrespective of B cell numbers, and comparable to healthy participants. RBD-IgG titres, but not tetramer+ T cell frequencies, positively correlated with B cell numbers. Vaccinated haematology patients with breakthrough infections had higher RBD-specific IgG antibody responses, while T cell responses were indistinguishable between infected and non-infected individuals in both patient and healthy groups. Overall, COVID-19 vaccination induces robust T-cell immunity in haematology patients of varying diseases and treatments, irrespective of their B-cell numbers and antibody response.