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
- Albert Einstein College of Medicine, United States
- Icahn School of Medicine at Mount Sinai, United States
- Montefiore Medical Center, United States
- Euroimmun, United States
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.
Funding: Leukemia lymphoma society, National Cancer Institute.
Clinical trial identifier: NCT05016622.
Data availability
The data for this clinical trial contains protected health information for the participants that includes a large amount of information as to specific dates/treatments/cancer diagnoses. Therefore, it is prudent to protect this information and it does not seem appropriate to put the information out in the public domain. For example- patients' specific cancer diagnoses, treatment received, COVID-19 vaccine dates can be viewed as sensitive information in the aggregate. If we remove this detailed information from the dataset then the dataset would end up being very limited and not useful for any researcher. Therefore, we believe that making the dataset available through the corresponding author based on individual well-supported requests will allow researchers access to complete data while protecting potentially identifiable patient-level information from the public domain. We are more than happy to share the deidentified database with the reviewers/editors (for review purposes only). If an interested researcher wishes to acquire the data, the aforementioned de-identified dataset can be made available by contacting the corresponding author of the study. While there are no restrictions on data usage per se, we request that future research be done in accordance with standardized guidelines and with local ethics approval. The code is already deposited in GitHubCode availability statement : Computer code has been deposited in GitHub and can be found at https://github.com/kith-pradhan/CovidBooster and https://github.com/kith-pradhan/CovidBooster4th
Article and author information
Author details
Funding
National Cancer Institute (3P30CA013330-49S3)
- Balazs Halmos
NCI Community Oncology outreach program (2UG1CA189859-06)
- Balazs Halmos
leukemia lymphoma society
- Amit K Verma
Centers of Excellence for Influenza Research and Surveillance (HHSN272201400008C)
- Florian Krammer
Centers of Excellence for Influenza Research and Response (75N93021C00014)
- Florian Krammer
Collaborative Influenza Vaccine Innovation Centers (75N93019C00051)
- Florian Krammer
National Cancer Institute (75N91019D00024)
- Florian Krammer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Ethics statement:The study was approved by Montefiore-Einstein institutional review board (IRB# 2021-13204). Participants were recruited after referral to the study from their treating oncologists. At the consent visit, patients were provided with a study overview including initial lab draw, vaccine appointment and follow-up at pre-specified time points. The informed consent document included consent for research samples and consent to protect confidential patient information by the personnel approved under the IRB. Any person not involved with the research study did not have access to patient identifying data. De-identified data was allowed to be shared with collaborators and findings from the study be published. The informed consent document also included consent for a future research lab draw should an improved test for SARS-CoV-2 immunity became available. Finally, the consent included patient's right to withdraw from the study at any time. The patient was provided with a copy of the signed informed consent.
Copyright
© 2023, Thakkar et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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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
eLife 12:e83694.
https://doi.org/10.7554/eLife.83694
Further reading
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Preeclampsia (PE), a major cause of maternal and perinatal mortality with highly heterogeneous causes and symptoms, is usually complicated by gestational diabetes mellitus (GDM). However, a comprehensive understanding of the immune microenvironment in the placenta of PE and the differences between PE and GDM is still lacking. In this study, cytometry by time of flight indicated that the frequencies of memory-like Th17 cells (CD45RA−CCR7+IL-17A+CD4+), memory-like CD8+ T cells (CD38+CXCR3−CCR7+Helios−CD127−CD8+) and pro-inflam Macs (CD206−CD163−CD38midCD107alowCD86midHLA-DRmidCD14+) were increased, while the frequencies of anti-inflam Macs (CD206+CD163−CD86midCD33+HLA-DR+CD14+) and granulocyte myeloid-derived suppressor cells (gMDSCs, CD11b+CD15hiHLA-DRlow) were decreased in the placenta of PE compared with that of normal pregnancy (NP), but not in that of GDM or GDM&PE. The pro-inflam Macs were positively correlated with memory-like Th17 cells and memory-like CD8+ T cells but negatively correlated with gMDSCs. Single-cell RNA sequencing revealed that transferring the F4/80+CD206− pro-inflam Macs with a Folr2+Ccl7+Ccl8+C1qa+C1qb+C1qc+ phenotype from the uterus of PE mice to normal pregnant mice induced the production of memory-like IL-17a+Rora+Il1r1+TNF+Cxcr6+S100a4+CD44+ Th17 cells via IGF1–IGF1R, which contributed to the development and recurrence of PE. Pro-inflam Macs also induced the production of memory-like CD8+ T cells but inhibited the production of Ly6g+S100a8+S100a9+Retnlg+Wfdc21+ gMDSCs at the maternal–fetal interface, leading to PE-like symptoms in mice. In conclusion, this study revealed the PE-specific immune cell network, which was regulated by pro-inflam Macs, providing new ideas about the pathogenesis of PE.
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Background: Several fields have described low reproducibility of scientific research and poor accessibility in research reporting practices. Although previous reports have investigated accessible reporting practices that lead to reproducible research in other fields, to date, no study has explored the extent of accessible and reproducible research practices in cardiovascular science literature.
Methods: To study accessibility and reproducibility in cardiovascular research reporting, we screened 639 randomly selected articles published in 2019 in three top cardiovascular science publications: Circulation, the European Heart Journal, and the Journal of the American College of Cardiology (JACC). Of those 639 articles, 393 were empirical research articles. We screened each paper for accessible and reproducible research practices using a set of accessibility criteria including protocol, materials, data, and analysis script availability, as well as accessibility of the publication itself. We also quantified the consistency of open research practices within and across cardiovascular study types and journal formats.
Results: We identified that fewer than 2% of cardiovascular research publications provide sufficient resources (materials, methods, data, and analysis scripts) to fully reproduce their studies. Of the 639 articles screened, 393 were empirical research studies for which reproducibility could be assessed using our protocol, as opposed to commentaries or reviews. After calculating an accessibility score as a measure of the extent to which an article makes its resources available, we also showed that the level of accessibility varies across study types with a score of 0.08 for Case Studies or Case Series and 0.39 for Clinical Trials (p = 5.500E-5) and across journals (0.19 through 0.34, p = 1.230E-2). We further showed that there are significant differences in which study types share which resources.
Conclusion: Although the degree to which reproducible reporting practices are present in publications varies significantly across journals and study types, current cardiovascular science reports frequently do not provide sufficient materials, protocols, data, or analysis information to reproduce a study. In the future, having higher standards of accessibility mandated by either journals or funding bodies will help increase the reproducibility of cardiovascular research.
Funding: Authors Gabriel Heckerman, Arely Campos-Melendez, and Chisomaga Ekwueme were supported by an NIH R25 grant from the National Heart, Lung and Blood Institute (R25HL147666). Eileen Tzng was supported by an AHA Institutional Training Award fellowship (18UFEL33960207).
