Abstract
Ehmsen et al. evaluate the neutralizing capacity to current SARS-CoV-2 variants in patients with cancer before and after receiving the BNT162b2 bivalent mRNA vaccine booster. Bivalent vaccine provides some protection against BQ.1.1 but fails to protect against XBB.1 and XBB.1.5 in patients with cancer.
Main text
Updated bivalent mRNA COVID-19 vaccines targeting both ancestral SARS-CoV-2 and subvariant Omicron BA.4/BA.5 were approved in the United States or Europe in fall 2022. Initially, this vaccine was given to individuals at high risk and later made available to the general population. Concurrently, winter has seen the emergence of new Omicron subvariants, including the now globally dominant BQ.1.1 (January 2023), XBB.1, and most recently, XBB.1.5, which is rapidly expanding in North America.1
The fast progression of these subvariants suggests strong immune-evasive properties and questions whether the updated bivalent vaccines still provide protection to those most vulnerable.
We measured SARS-CoV-2 spike-specific immunoglobulin G (IgG) (anti-S) antibody levels and authentic virus neutralization of BQ.1.1 in patients with cancer after the fourth BNT162b2 mRNA monovalent booster (Pfizer-BioNTech) and before and after the BNT162b2 bivalent mRNA vaccine (Pfizer-BioNTech). The 114 patients (101 hematologic and 13 solid cancers) were selected from a larger cohort of 530 patients with cancer based on insufficient anti-S responses after the second vaccination (Tables S1 and S2).2 , 3
The patients’ anti-S levels significantly increased, and the overall neutralizing capacity toward BQ.1.1 significantly enhanced after the bivalent vaccine compared to after the fourth monovalent and before the bivalent vaccine (p < 0.001). Based on a predetermined threshold titer of 1:8.8 for Omicron subvariants,4 the bivalent vaccine provided neutralizing capacity against BQ.1.1 in 55% (n = 24) of patients with cancer who lacked a protective response prior to vaccination (n = 44) (Figures S1A and S1B).
In a representative subpopulation (n = 19), neutralizing capacities were also measured against ancestral, BA.5, and XBB subvariants (Figure S1C). After the bivalent vaccine, 10.5% (2/19) remained below the threshold against BQ.1.1, and a larger fraction (8/19, 42%; 6/19, 32%) remained below the threshold against XBB.1 and XBB.1.5, respectively. When comparing the estimated geometric mean titer for all four SARS-CoV-2 strains analyzed, XBB.1 and XBB.1.5 are strikingly low at only 1:13 and 1:14, respectively, in contrast to 1:344, 1:83, and 1:39 for the ancestral, BA.5, and BQ.1.1, respectively. The gradual reduction in neutralization titer against the newer variants is shown for each of the 19 patients in Figure S1D, and change in anti-S antibody levels during recent vaccination course is shown in Figure S1E.
Recent neutralization data suggest that healthy individuals benefit from the bivalent mRNA vaccine against recent subvariants, including BQ.1.1 and XBB.5 Our data highlight that the bivalent vaccine largely fails to protect against XBB.1 and XBB.1.5 in a main target group, immune-deficient cancer patients, despite providing some protection against the currently dominant BQ.1.1 in these individuals. The drastic progression of highly transmissible SARS-CoV-2 subvariants, such as XBB, questions the long-term efficacy of the current bivalent vaccines and emphasizes the need for further updated vaccines and effective antivirals.
Acknowledgments
The study was supported by a grant from the Odense University Hospital Research Council. The funder had no role in study design, patient recruitment, data collection, data analysis, data interpretation, or writing of the report. We want to express our sincere gratitude to the participants of the study; to laboratory technicians at the Odense University Hospital, Department of Oncology for technical assistance with the blood samples; to the Clinical Experimental Unit, Department of Oncology, Odense University Hospital for assistance with the recruitment of patients; and to Yaseelan Palarasah and Jette Hvelplund for providing VERO E6 cells. We thank M.K. Occhipinti for editorial assistance.
Author contributions
Conceptualization, S.E., R.M.P., L.L.B., T.E.A., and H.J.D.; methodology, S.E., L.L.B., D.K.H., T.G.J., and T.V.S.; data curation and formal analysis, S.E., L.L.B., A.A., A.K., D.K.H., T.G.J., and R.M.P; investigation, S.E., R.M.P., L.L.B., A.A., A.K., T.G.J., S.S.J., H.F., T.E.A., and H.J.D; writing – original draft, S.E., R.M.P., T.E.A., and H.J.D.; writing – review & editing, all authors; funding acquisition, H.J.D.; resources, R.M.P., T.G.J., T.E.A., and H.J.D.; supervision, R.M.P., T.E.A., and H.J.D. All authors contributed equally. More than one author has directly accessed and verified the underlying data reported in the manuscript.
Declaration of interests
The authors declare no competing interests.
Footnotes
Supplemental information can be found online at https://doi.org/10.1016/j.ccell.2023.02.003.
Supplemental information
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