Safety and Immunogenicity of the BNT162b2 mRNA Covid-19 Vaccine in Patients after Allogeneic HCT or CD19-based CART therapy – a Single Center Prospective Cohort Study

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Abstract

Data are scarce regarding both safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy, thus we prospectively evaluated these 2 domains in patients receiving this vaccine after allogeneic HCT (n=66) or after CD19-based CART therapy (n=14). Overall, vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in minority of the patients. 12% (after first dose) and 10% (after second dose) of the patients developed cytopenia and there were 3 cases GVHD exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. On cox regression model, longer time from infusion of cells, female sex, and higher CD19 ⁺ cells were associated with a positive humoral response, whereas higher CD4 ⁺/CD8 ⁺ ratiowas correlated with a positive cellular response, confirmed by ELISpot test. We conclude that BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed, hence, patients should be closely monitored.

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

Fernando P Polack, Stephen J. Thomas, Nicholas R.E. Kitchin … (2023)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently. Methods In an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety. Results A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups. Conclusions A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T-cell responses

Ugur Sahin, Alexander Muik, Evelyna Derhovanessian … (2020)

An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18-55 years of age. Two doses of 1-50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-μg dose) to 3.5-fold (50-μg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.

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Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

Evan J Anderson, Nadine G Rouphael, Alicia T. Widge … (2020)

Abstract Background Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. Methods We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. Results Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. Conclusions In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.)

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Author and article information

Journal

Journal ID (nlm-ta): Transplant Cell Ther

Journal ID (iso-abbrev): Transplant Cell Ther

Title: Transplantation and Cellular Therapy

Publisher: Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

ISSN (Print): 2666-6375

ISSN (Electronic): 2666-6367

Publication date PMC-release: 30 June 2021

Publication date (Electronic): 30 June 2021

Affiliations

[a ]BMT Unit, Tel Aviv Sourasky Medical Center, Israel

[b ]Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

[c ]Allergy and Clinical Immunology Unit, Department of Medicine, Tel Aviv Sourasky Medical Center, Israel

[d ]Endocrinology Laboratory, Tel Aviv Sourasky Medical Center, Israel

[e ]Hematology Ward, Shamir Medical Center (Assaf Haraofeh)

[f ]Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Israel

Author notes

[* ]Corresponding author at: Bone Marrow Transplantation Unit, Tel Aviv (Sourasky) Medical Center, Tel Aviv, Israel.

Article

Publisher Item ID: S2666-6367(21)01027-7

DOI: 10.1016/j.jtct.2021.06.024

PMC ID: 8242200

PubMed ID: 34214738

SO-VID: f81297b7-108a-47fd-91f5-f499f0d1d498

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Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Safety and Immunogenicity of the BNT162b2 mRNA Covid-19 Vaccine in Patients after Allogeneic HCT or CD19-based CART therapy – a Single Center Prospective Cohort Study

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Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T-cell responses

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

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