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Selective suppression of de novo SARS-CoV-2 vaccine antibody responses in patients with cancer on B cell–targeted therapy
Joseph H. Azar, John P. Evans, Madison H. Sikorski, Karthik B. Chakravarthy, Selah McKenney, Ian Carmody, Cong Zeng, Rachael Teodorescu, No-Joon Song, Jamie L. Hamon, Donna Bucci, Maria Velegraki, Chelsea Bolyard, Kevin P. Weller, Sarah A. Reisinger, Seema A. Bhat, Kami J. Maddocks, Nathan Denlinger, Narendranath Epperla, Richard J. Gumina, Anastasia N. Vlasova, Eugene M. Oltz, Linda J. Saif, Dongjun Chung, Jennifer A. Woyach, Peter G. Shields, Shan-Lu Liu, Zihai Li, Mark P. Rubinstein
Joseph H. Azar, John P. Evans, Madison H. Sikorski, Karthik B. Chakravarthy, Selah McKenney, Ian Carmody, Cong Zeng, Rachael Teodorescu, No-Joon Song, Jamie L. Hamon, Donna Bucci, Maria Velegraki, Chelsea Bolyard, Kevin P. Weller, Sarah A. Reisinger, Seema A. Bhat, Kami J. Maddocks, Nathan Denlinger, Narendranath Epperla, Richard J. Gumina, Anastasia N. Vlasova, Eugene M. Oltz, Linda J. Saif, Dongjun Chung, Jennifer A. Woyach, Peter G. Shields, Shan-Lu Liu, Zihai Li, Mark P. Rubinstein
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Research Article COVID-19 Oncology

Selective suppression of de novo SARS-CoV-2 vaccine antibody responses in patients with cancer on B cell–targeted therapy

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Abstract

We assessed vaccine-induced antibody responses to the SARS-CoV-2 ancestral virus and Omicron variant before and after booster immunization in 57 patients with B cell malignancies. Over one-third of vaccinated patients at the pre-booster time point were seronegative, and these patients were predominantly on active cancer therapies such as anti-CD20 monoclonal antibody. While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the overall booster benefit was disproportionately evident in patients already seropositive and not receiving active therapy. While ancestral virus– and Omicron variant–reactive antibody levels among individual patients were largely concordant, neutralizing antibodies against Omicron tended to be reduced. Interestingly, in all patients, including those unable to generate detectable antibodies against SARS-CoV-2 spike, we observed comparable levels of EBV- and influenza-reactive antibodies, demonstrating that B cell–targeting therapies primarily impair de novo but not preexisting antibody levels. These findings support rationale for vaccination before cancer treatment.

Authors

Joseph H. Azar, John P. Evans, Madison H. Sikorski, Karthik B. Chakravarthy, Selah McKenney, Ian Carmody, Cong Zeng, Rachael Teodorescu, No-Joon Song, Jamie L. Hamon, Donna Bucci, Maria Velegraki, Chelsea Bolyard, Kevin P. Weller, Sarah A. Reisinger, Seema A. Bhat, Kami J. Maddocks, Nathan Denlinger, Narendranath Epperla, Richard J. Gumina, Anastasia N. Vlasova, Eugene M. Oltz, Linda J. Saif, Dongjun Chung, Jennifer A. Woyach, Peter G. Shields, Shan-Lu Liu, Zihai Li, Mark P. Rubinstein

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Figure 3

ELISA and viral neutralization assay depict variable antibody response to the ancestral and Omicron SARS-CoV-2 strains before and after booster vaccination in patients with hematological cancer.

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ELISA and viral neutralization assay depict variable antibody response t...
(A–C) Area under the curve (AUC) for all patients (A), patients without active therapy (B), and patients with active therapy (C). (D–F) Same as A–C except showing the 50% neutralization titer (NT50). For all data, each symbol represents a time point at which serum was isolated, and the line connects individual patients. The number above each graph represent arithmetic mean. ANOVA was used to compare between pre-booster ancestral, post-booster ancestral, pre-booster Omicron, and post-booster Omicron NT50/AUC values of the same patient. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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