Comprehensive humoral and cellular immune responses to COVID-19 vaccination in adults with cancer
Amy Body, Luxi Lal, Sriganesh Srihari, C. Raina MacIntyre, Jim Buttery, Elizabeth Ahern, Stephen Opat, Michael F. Leahy, Nada Hamad, Vivienne Milch, Stuart Turville, Corey Smith, Katie E. Lineburg, Zin Naing, William D. Rawlinson, Eva Segelov
Abstract
BACKGROUND: The COVID-19 pandemic has significantly impacted people with cancer. Initial vaccine studies excluded patients with malignancy. Immunocompromised individuals remain vulnerable to SARS-CoV-2, necessitating detailed understanding of vaccine response. The epidemiology of COVID-19 in Australia offered unique opportunities to study cancer populations with minimal community exposure to SARS-CoV-2. METHODS: SerOzNET prospectively examined previously unvaccinated patients with solid and haematological malignancies receiving up to five COVID-19 vaccine doses. Antibody response was measured by live virus neutralisation assay (neutralising antibody (NAb); positive titre ≥1:20; study primary endpoint) and commercial assay. T cell response was measured by cytometric bead array; positive defined as interferon gamma (IFN-γ) ≥10 pg/mL in response to Spike antigen. Patient and physician-reported adverse events were secondary endpoints. OUTCOMES: 395 adults were enrolled prior to receiving mRNA vaccine (BNT162b2 = 347; mRNA-1273 = 1) or viral vector vaccine (ChadOx1-S = 43) for initial two-dose course, plus up to three additional doses. Median age was 58 years (range: 20-85); 60 % were female; 35 % had haematological malignancy, 2/395 (0.5 %) had baseline positive nucleocapsid antibody indicating prior SARS-CoV-2 exposure. NAb response post dose three was demonstrated in 84 % overall; 96 % of patients with solid cancers and 64 % with haematological cancer (p < 0·001). Risk factors for non-response were haematological cancer and anti B-cell therapies. Some patients with haematological cancer seroconverted for the first time after the fourth or fifth dose. IFN-γ response was seen in many patients with haematological cancer who lacked NAb response. Serious adverse events were rare. COVID-19 infection occurred in 29 % with no deaths. INTERPRETATION: COVID-19 vaccination elicits B and T cell responses in patients with solid and haematological cancers, with an acceptable safety profile. A significant proportion of haematological cancer patients require >3 doses to elicit NAb, with many demonstrating T cell response, which may be an alternative pathway of immune protection.