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.
Metrics
-
- 1,129
- views
-
- 204
- downloads
-
- 14
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
-
- Medicine
Background:
Approximately one-third of patients with HER2-positive breast cancer experienced recurrence within 10 years after receiving 1 year of adjuvant trastuzumab. The ExteNET study showed that 1 year of extended adjuvant neratinib after trastuzumab-based adjuvant therapy could reduce invasive disease-free survival (iDFS) events compared with placebo. This study investigated the efficacy and safety of pyrotinib, an irreversible pan-HER receptor tyrosine kinase inhibitor, after trastuzumab-based adjuvant therapy in patients with high-risk, HER2-positive early or locally advanced breast cancer.
Methods:
This multicenter phase II trial was conducted at 23 centers in China. After enrollment, patients received 1 year of extended adjuvant pyrotinib (400 mg/day), which should be initiated within 6 months after the completion of 1-year adjuvant therapy (trastuzumab alone or plus pertuzumab). The primary endpoint was 2-year iDFS rate.
Results:
Between January 2019 and February 2022, 141 eligible women were enrolled and treated. As of October 10, 2022, the median follow-up was 24 (interquartile range, 18.0–34.0) months. The 2-year iDFS rate was 94.59% (95% confidence interval [CI]: 88.97–97.38) in all patients, 94.90% (95% CI: 86.97–98.06) in patients who completed 1-year treatment, 90.32% (95% CI: 72.93–96.77) in patients who completed only 6-month treatment, 96.74% (95% CI: 87.57–99.18) in the hormone receptor (HR)-positive subgroup, 92.77% (95% CI: 83.48–96.93) in the HR-negative subgroup, 96.88% (95% CI: 79.82–99.55) in the lymph node-negative subgroup, 93.85% (95% CI: 86.81–97.20) in the lymph node-positive subgroup, 97.30% (95% CI: 82.32–99.61) in patients with adjuvant trastuzumab plus pertuzumab, and 93.48% (95% CI: 86.06–97.02) in patients with adjuvant trastuzumab. The most common adverse events were diarrhea (79.4%), fatigue (36.9%), lymphocyte count decreased (36.9%), nausea (33.3%), and hand-foot syndrome (33.3%).
Conclusions:
Extended adjuvant pyrotinib administrated after trastuzumab-based adjuvant therapy showed promising efficacy in patients with high-risk HER2-positive breast cancer. The follow-up is ongoing to determine the long-term benefit.
Funding:
No external funding was received for this work.
Clinical trial number:
ClinicalTrials.gov: NCT05880927
-
- Immunology and Inflammation
- Medicine
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.
