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.

Autor:	Thakkar A; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Pradhan K; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, United States., Duva B; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Carreno JM; Department 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., Sahu S; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Thiruthuvanathan V; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Campbell S; Department of Pathology, Montefiore Medical Center, Bronx, United States., Gallego S; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Bhagat TD; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Rivera J; Department of Medicine, Albert Einstein College of Medicine, Bronx, United States., Choudhary G; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Olea R; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Sabalza M; Euroimmun, Mountain Lakes, United States., Shapiro LC; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Lee M; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Quinn R; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Mantzaris I; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Chu E; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Will B; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Pirofski LA; Department of Medicine, Albert Einstein College of Medicine, Bronx, United States., Krammer F; Department 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 States., Verma A; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States., Halmos B; Department of Oncology, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Mar 28; Vol. 12. Date of Electronic Publication: 2023 Mar 28.
DOI:	10.7554/eLife.83694
Abstrakt:	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. Competing Interests: AT, KP, BD, JC, SS, VT, SC, SG, TB, JR, GC, RO, LS, ML, RQ, IM, EC, BW, LP, BH No competing interests declared, MS is affiliated with EUROIMMUN and has no financial interests to declare, FK The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which list Florian Krammer as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020), and is currently consulting for Pfizer, Seqirus, 3rd Rock Ventures and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2.(Serological Assay, U.S. Application Serial No. 17/913,783, NDV-HXP-S, U.S. Application Serial No. 17/922,777), AV Reviewing editor, eLife (© 2023, Thakkar et al.)
Databáze:	MEDLINE
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