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Fourth Vaccine Dose Increases in Humoral Immunity Against Omicron Variants in Patients with Cancer

Passive immunisation with tixagevimab and cilgavimab may not be effective
03 Oct 2022
COVID-19 and Cancer

To analyze variant-specific humoral immunity after active and passive SARS-CoV-2 immunisation in patients with cancer, a group of researchers from the Medical University of Vienna and the Südtiroler Sanitätsbetrieb compared antibody levels against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 hu-1 and Omicron variants BA.1 or BA.4 after the third and fourth vaccine doses or administration of tixagevimab and cilgavimab. Findings from this small cohort study suggest that passive immunisation with tixagevimab and cilgavimab may not be effective in blocking Omicron variants BA.1 and BA.4. However, there was an increase in humoral immunity after the fourth vaccine dose. Findings are published by Drs. Maximilian J. Mair and Matthias Preusser of the Division of Oncology and Christian Doppler Laboratory for Personalised Immunotherapy, Department of Medicine I, Medical University of Vienna in Vienna, Austria and colleagues on 22 September 2022 in the JAMA Oncology.

The authors wrote in a research letter that levels of neutralising antibodies against variants of concern, including Delta and Omicron, are lower in patients with cancer. Fourth vaccine dose or administration of monoclonal neutralising antibodies, such as tixagevimab and cilgavimab, is being considered, although data supporting this strategy are limited, especially in the context of currently circulating Omicron variants.

The study team included 72 patients, who were in median 74 years old (range, 48-89). There were 47 men (65.3%) and 25 women (34.7%). Of these patients, 54 (75.0%) received a fourth vaccine dose, 21 with solid tumours, and 33 with haematologic malignancy. A total, 18 patients (25.0%) received tixagevimab and cilgavimab as passive immunisation.

The study team analyzed the levels of anti-RBD antibodies after the third and fourth vaccine doses. Median (range) anti-RBD levels increased in patients with haematological malignancies undergoing B cell–targeted therapy, particularly against Omicron variants BA.1 and BA.4. There were no differences in antibody levels among patients with other haematological diseases. There was also increase in median (range) anti-RBD levels in patients with solid tumours for all investigated variants of concern before versus after the fourth vaccine dose, including hu-1, BA.1, and BA.4.

The inhibitory potential against RBD and ACE-2 interaction was generally higher after the fourth than after the third vaccine dose, especially for variants BA.1 and BA.4, in patients with haematological and solid tumours. In terms of inhibitory capacity of tixagevimab and cilgavimab as a preexposure prophylaxis for RBD and ACE-2 interaction, the study team observed a difference according to the investigated variant of concern, with median inhibition of 99.9% for hu-1, 34.9% for BA.1, and 15.4% for BA.4.

The authors commented that further prospective studies are needed to confirm these findings and guide recommendations for COVID-19 vaccination. However, they do suppport timely administration of a fourth vaccine dose to increase the immunity against currently circulating Omicron variants.

This study was funded by the Austrian Federal Ministry for Digital and Economic Affairs; the National Foundation for Research, Technology and Development; and the Christian Doppler Research Association. This study was also funded from the research budget of the Medical University of Vienna and the budget of the Südtiroler Sanitätsbetrieb.


Mair MJ, Mitterer M, Gattinger P, et al. Inhibition of SARS-CoV-2 Omicron BA.1 and BA.4 Variants After Fourth Vaccination or Tixagevimab and Cilgavimab Administration in Patients With Cancer. JAMA Oncology; Published online, 22 September 2022. doi:10.1001/jamaoncol.2022.4226

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