Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial

Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering ‘booster’ doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the eff...

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Main Authors: Astha Thakkar, Kith Pradhan, Benjamin Duva, Juan Manuel Carreno, Srabani Sahu, Victor Thiruthuvanathan, Sean Campbell, Sonia Gallego, Tushar D Bhagat, Johanna Rivera, Gaurav Choudhary, Raul Olea, Maite Sabalza, Lauren C Shapiro, Matthew Lee, Ryann Quinn, Ioannis Mantzaris, Edward Chu, Britta Will, Liise-anne Pirofski, Florian Krammer, Amit Verma, Balazs Halmos
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/83694
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author Astha Thakkar
Kith Pradhan
Benjamin Duva
Juan Manuel Carreno
Srabani Sahu
Victor Thiruthuvanathan
Sean Campbell
Sonia Gallego
Tushar D Bhagat
Johanna Rivera
Gaurav Choudhary
Raul Olea
Maite Sabalza
Lauren C Shapiro
Matthew Lee
Ryann Quinn
Ioannis Mantzaris
Edward Chu
Britta Will
Liise-anne Pirofski
Florian Krammer
Amit Verma
Balazs Halmos
author_facet Astha Thakkar
Kith Pradhan
Benjamin Duva
Juan Manuel Carreno
Srabani Sahu
Victor Thiruthuvanathan
Sean Campbell
Sonia Gallego
Tushar D Bhagat
Johanna Rivera
Gaurav Choudhary
Raul Olea
Maite Sabalza
Lauren C Shapiro
Matthew Lee
Ryann Quinn
Ioannis Mantzaris
Edward Chu
Britta Will
Liise-anne Pirofski
Florian Krammer
Amit Verma
Balazs Halmos
author_sort Astha Thakkar
collection DOAJ
description Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering ‘booster’ doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population Methods: We conducted a prospective single arm clinical trial enrolling patients with cancer that had received two doses of mRNA or one dose of AD26.CoV2.S vaccine and administered a third dose of mRNA vaccine. We further enrolled patients that had no or low responses to three mRNA COVID vaccines and assessed the efficacy of a fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, which were again assessed at baseline and 4 weeks. Results: We demonstrate that a third dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination series. The immune response is durable as assessed by anti-SARS-CoV-2 (anti-S) antibody titers, T-cell activity, and neutralization activity against wild-type (WT) SARS-CoV2 and BA1.1.529 at 6 months of follow-up. A subset of severely immunocompromised hematologic malignancy patients that were unable to mount an adequate immune response (titer <1000 AU/mL) after the third dose and were treated with a fourth dose in a prospective clinical trial which led to adequate immune boost in 67% of patients. Low baseline IgM levels and CD19 counts were associated with inadequate seroconversion. Booster doses induced limited neutralization activity against the Omicron variant. Conclusions: These results indicate that third dose of COVID vaccine induces durable immunity in cancer patients and an additional dose can further stimulate immunity in a subset of patients with inadequate response. Funding: Leukemia Lymphoma Society, National Cancer Institute. Clinical trial number: NCT05016622.
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spelling doaj.art-6208af8c6b20451080ddc36e3a95392b2023-04-25T17:22:59ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.83694Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trialAstha Thakkar0https://orcid.org/0000-0001-7778-0752Kith Pradhan1Benjamin Duva2Juan Manuel Carreno3Srabani Sahu4Victor Thiruthuvanathan5Sean Campbell6Sonia Gallego7Tushar D Bhagat8Johanna Rivera9Gaurav Choudhary10https://orcid.org/0000-0001-5365-6706Raul Olea11Maite Sabalza12Lauren C Shapiro13Matthew Lee14Ryann Quinn15Ioannis Mantzaris16Edward Chu17Britta Will18Liise-anne Pirofski19Florian Krammer20Amit Verma21https://orcid.org/0000-0002-5408-1673Balazs Halmos22https://orcid.org/0000-0001-7548-8360Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United States; Center for Vaccine Research and Pandemic Preparedness (C-VARPP), Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Pathology, Montefiore Medical Center, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Medicine, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesEuroimmun, Mountain Lakes, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Medicine, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United States; Center for Vaccine Research and Pandemic Preparedness (C-VARPP), Icahn School of Medicine at Mount Sinai, New York, United States; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesDepartment of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United StatesBackground: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering ‘booster’ doses of COVID-19 vaccines beyond the standard two-dose series, for this group of patients. Therefore, studying the efficacy of these additional vaccine doses against SARS-CoV-2 and variants of concern is of utmost importance in this immunocompromised patient population Methods: We conducted a prospective single arm clinical trial enrolling patients with cancer that had received two doses of mRNA or one dose of AD26.CoV2.S vaccine and administered a third dose of mRNA vaccine. We further enrolled patients that had no or low responses to three mRNA COVID vaccines and assessed the efficacy of a fourth dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity, and neutralization activity, which were again assessed at baseline and 4 weeks. Results: We demonstrate that a third dose of COVID-19 vaccine leads to seroconversion in 57% of patients that were seronegative after primary vaccination series. The immune response is durable as assessed by anti-SARS-CoV-2 (anti-S) antibody titers, T-cell activity, and neutralization activity against wild-type (WT) SARS-CoV2 and BA1.1.529 at 6 months of follow-up. A subset of severely immunocompromised hematologic malignancy patients that were unable to mount an adequate immune response (titer <1000 AU/mL) after the third dose and were treated with a fourth dose in a prospective clinical trial which led to adequate immune boost in 67% of patients. Low baseline IgM levels and CD19 counts were associated with inadequate seroconversion. Booster doses induced limited neutralization activity against the Omicron variant. Conclusions: These results indicate that third dose of COVID vaccine induces durable immunity in cancer patients and an additional dose can further stimulate immunity in a subset of patients with inadequate response. Funding: Leukemia Lymphoma Society, National Cancer Institute. Clinical trial number: NCT05016622.https://elifesciences.org/articles/83694SARS CoV-2COVID-19vaccineimmunocompromisedcancer
spellingShingle Astha Thakkar
Kith Pradhan
Benjamin Duva
Juan Manuel Carreno
Srabani Sahu
Victor Thiruthuvanathan
Sean Campbell
Sonia Gallego
Tushar D Bhagat
Johanna Rivera
Gaurav Choudhary
Raul Olea
Maite Sabalza
Lauren C Shapiro
Matthew Lee
Ryann Quinn
Ioannis Mantzaris
Edward Chu
Britta Will
Liise-anne Pirofski
Florian Krammer
Amit Verma
Balazs Halmos
Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial
eLife
SARS CoV-2
COVID-19
vaccine
immunocompromised
cancer
title Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial
title_full Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial
title_fullStr Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial
title_full_unstemmed Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial
title_short Study of efficacy and longevity of immune response to third and fourth doses of COVID-19 vaccines in patients with cancer: A single arm clinical trial
title_sort study of efficacy and longevity of immune response to third and fourth doses of covid 19 vaccines in patients with cancer a single arm clinical trial
topic SARS CoV-2
COVID-19
vaccine
immunocompromised
cancer
url https://elifesciences.org/articles/83694
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