@article{fa285910c9c64909b417cbff2d542fd1,
title = "Study of efficacy and longevity of immune response to 3rd and 4th doses of COVID-19 vaccines in patients with cancer: a single arm clinical trial",
abstract = "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 2-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 3rd 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 4th dose of mRNA vaccine. Efficacy was assessed by changes in anti-spike antibody, T-cell activity and neutralization activity were again assessed at baseline and 4 weeks. Results: We demonstrate that a 3rd 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-S antibody titers, T-cell activity and neutralization activity against wild-type 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 3rd dose and were treated with a 4th 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 3rd 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. .",
keywords = "Booster, COVID-19, Cancer, Vaccine",
author = "Astha Thakkar and Kith Pradhan and Benjamin Duva and Carre{\~n}o, {Juan Manuel} and Srabani Sahu and Victor Thiruthuvanathan and Sean Campbell and Sonia Gallego and Bhagat, {Tushar D.} and Johanna Rivera and Gaurav Choudhary and Raul Olea and Maite Sabalza and Shapiro, {Lauren C.} and Matthew Lee and Ryann Quinn and Ioannis Mantzaris and Edward Chu and Britta Will and Pirofski, {Liise Anne} and Florian Krammer and Amit Verma and Balazs Halmos",
note = "Funding Information: A cknowledgements: This study was supported with funding from the National Cancer Institute G rant 3P30CA013330-49S3 and NCORP Grant 2UG1CA189859-06. The authors also a cknowledge support from the Jane and Myles Dempsey Family and Leukemia Lymphoma S ociety. The funders had no role in study design, data collection and analysis, decision to p ublish, or preparation of the manuscript. Work in the Krammer laboratory was partially funded b y the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # H HSN272201400008C), the Centers of Excellence for Influenza Research and Response ( CEIRR, contract # 75N93021C00014), by the Collaborative Influenza Vaccine Innovation C enters (CIVICs contract # 75N93019C00051) and by institutional funds. Finally, this effort was a lso supported by the Serological Sciences Network (SeroNet) in part with Federal funds from t he National Cancer Institute, National Institutes of Health, under Contract No. 7 5N91019D00024, Task Order No. 75N91020F00003. The content of this publication does not n ecessarily reflect the views or policies of the Department of Health and Human Services, nor d oes mention of trade names, commercial products or organizations imply endorsement by the U .S. Government. Funding Information: This study was supported with funding from the National Cancer Institute Grant 3P30CA013330-49S3 and NCORP Grant 2UG1CA189859-06. The authors also acknowledge support from the Jane and Myles Dempsey Family and Leukemia Lymphoma Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Work in the Krammer laboratory was partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the Centers of Excellence for Influenza Research and Response (CEIRR, contract # 75N93021C00014), by the Collaborative Influenza Vaccine Innovation Centers (CIVICs contract # 75N93019C00051) and by institutional funds. Finally, this effort was also supported by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. Publisher Copyright: {\textcopyright} 2023, eLife Sciences Publications Ltd. All rights reserved.",
year = "2023",
month = mar,
doi = "10.7554/elife.83694",
language = "English (US)",
volume = "12",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}
