TY - JOUR
T1 - Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors
AU - Shroff, Rachna T.
AU - Chalasani, Pavani
AU - Wei, Ran
AU - Pennington, Daniel
AU - Quirk, Grace
AU - Schoenle, Marta V.
AU - Peyton, Kameron L.
AU - Uhrlaub, Jennifer L.
AU - Ripperger, Tyler J.
AU - Jergović, Mladen
AU - Dalgai, Shelby
AU - Wolf, Alexander
AU - Whitmer, Rebecca
AU - Hammad, Hytham
AU - Carrier, Amy
AU - Scott, Aaron J.
AU - Nikolich-Žugich, Janko
AU - Worobey, Michael
AU - Sprissler, Ryan
AU - Dake, Michael
AU - LaFleur, Bonnie J.
AU - Bhattacharya, Deepta
N1 - Funding Information:
This work was supported by National Institutes of Health grants R01AI099108 and R01AI129945 (D.B.), R37AG020719 (J.N.Z.) and T32AG058503 (T.J.R.) and by University of Arizona funds (D.B. and R.S.). We thank M. Pepper (University of Washington) and J. Netland (University of Washington) for technical assistance with tetramer stains. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Schema in Fig. 1a and Extended Data Fig. 9a were created using BioRender.
Funding Information:
Sana Biotechnology has licensed intellectual property of D.B. and Washington University in St. Louis. D.B. is a co-founder of Clade Therapeutics. B.J.L. has a financial interest in Cofactor Genomics and Iron Horse Dx. P.C. receives research funding from Pfizer, BioAtla, Zentalis, Genentech, Eli Lilly, Phoenix Molecular Designs, Amgen, Radius Pharmaceuticals, Carrick Therapeutics and Angiochem and served on advisory boards for Novartis, Eli Lilly, Zentalis, AstraZeneca, Amgen, Bayer, Asthenex, Prosigna, Heron, Puma Biotechnology and Oncosec. R.T.S. receives research funding from Merck, Rafael Pharmaceuticals, ImmunoVaccine, Bayer, SeaGen, Exelixis, Pieris, LOXO Oncology, Novocure, NuCana and QED and has served as a consultant/advisor to Merck, Servier, AstraZeneca, EMD Serono, Taiho, QED, Incyte, Genentech and Basilea. The remaining authors declare no competing interests, and no authors are employees of relevant companies.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/11
Y1 - 2021/11
N2 - Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 (NCT04936997); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.
AB - Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 (NCT04936997); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.
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U2 - 10.1038/s41591-021-01542-z
DO - 10.1038/s41591-021-01542-z
M3 - Article
C2 - 34594036
AN - SCOPUS:85116395383
SN - 1078-8956
VL - 27
SP - 2002
EP - 2011
JO - Nature Medicine
JF - Nature Medicine
IS - 11
ER -