Herpes zoster after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in actively treated cancer patients: a prospective study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Several concerns have been raised about a causal relationship between COVID-19 mRNA-based vaccines and the development of herpes zoster (HZ). We performed a prospective analysis of the Vax-On-Third-Profile study to investigate the incidence of HZ after the third dose of mRNA-BNT162b2 (tozinameran) and its correlation with immune responses. Patients who had received a booster dose and had been actively treated for at least 8 weeks were eligible. Serologic assessment was performed before the third dose of tozinameran (timepoint-1) and 4 weeks later (timepoint-2). We also assessed the incidence of SARS-CoV-2 breakthrough infections at predefined time points. The current analysis included 310 patients, of whom 109 (35.2%) and 111 (35.8%) were being treated with targeted therapies and cytotoxic chemotherapy, respectively. All participants received a third dose of tozinameran between September 26 and October 30, 2021. After a mean follow-up of 17.3 (IQR 15.1–18.4) months, HZ occurred in 8 recipients, for a cumulative incidence of 2.6%, and an incidence rate of 0.310 per person-year (95% CI 0.267–0.333). All HZ cases occurred within 30 days of booster dosing (range 5–29 days), with a median time to onset of 15 (IQR 9–22) days. Among the 7 patients (2.2%) who also contracted a SARS-CoV-2 infection, all cases preceded COVID-19 outbreaks. No instances of complicated HZ were reported. In multivariate analysis, impaired T helper and T cytotoxic cell counts independently correlated with HZ occurrence. These findings provide the first evidence that cancer patients on active treatment have a not negligible risk of developing HZ within 30 days after the third dose of tozinameran. The favorable clinical outcome of all observed cases confirms that protective effects of boosters in reducing the risk of severe COVID-19 outweigh the potential risk of HZ occurrence.

Supplementary Information

The online version contains supplementary material available at 10.1007/s10238-023-01263-2.

Related collections

Most cited references 45

Record: found
Abstract: found
Article: not found

Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting

Noam Barda, Noa Dagan, Yatir Ben-Shlomo … (2021)

Background Preapproval trials showed that messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations. An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed. Methods We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine. For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables. Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan–Meier estimator. To place these results in context, we performed a similar analysis involving SARS-CoV-2–infected persons matched to uninfected persons. The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses. Results In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons. Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2). SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia. Conclusions In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined. The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons). The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)

0 comments Cited 500 times     Rated -3 of 5. – based on 1 reviews

Bookmark

Record: found
Abstract: found
Article: not found

Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection

Ganesh Kolumam, Sunil Thomas, Lucas Thompson … (2005)

T cell expansion and memory formation are generally more effective when elicited by live organisms than by inactivated vaccines. Elucidation of the underlying mechanisms is important for vaccination and therapeutic strategies. We show that the massive expansion of antigen-specific CD8 T cells that occurs in response to viral infection is critically dependent on the direct action of type I interferons (IFN-Is) on CD8 T cells. By examining the response to infection with lymphocytic choriomeningitis virus using IFN-I receptor–deficient (IFN-IR0) and –sufficient CD8 T cells adoptively transferred into normal IFN-IR wild-type hosts, we show that the lack of direct CD8 T cell contact with IFN-I causes >99% reduction in their capacity to expand and generate memory cells. The diminished expansion of IFN-IR0 CD8 T cells was not caused by a defect in proliferation but by poor survival during the antigen-driven proliferation phase. Thus, IFN-IR signaling in CD8 T cells is critical for the generation of effector and memory cells in response to viral infection.

0 comments Cited 283 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

WHO International Standard for anti-SARS-CoV-2 immunoglobulin

Paul Kristiansen, Mark Page, Valentina Bernasconi … (2021)

The development timeline of COVID-19 vaccines is unprecedented, with more than 300 vaccine developers active worldwide. 1 Vaccine candidates developed with various technology platforms targeting different epitopes of SARS-CoV-2 are in the pipeline. Vaccine developers are using a range of immunoassays with different readouts to measure immune responses after vaccination, making comparisons of the immunogenicity of different COVID-19 vaccine candidates challenging. In April, 2020, in a joint effort, the Coalition for Epidemic Preparedness Innovations (CEPI), the National Institute for Biological Standards and Control (NIBSC), and WHO provided vaccine developers and the entire scientific community with a research reagent for an anti-SARS-CoV-2 antibody. The availability of this material was crucial for facilitating the development of diagnostics, vaccines, and therapeutic preparations. This effort was an initial response when NIBSC, in its capacity as a WHO collaborating centre, was working on the preparation of the WHO International Standards. This work included a collaborative study that was launched in July, 2020, to test serum samples and plasma samples sourced from convalescent patients with the aim of selecting the most suitable candidate material for the WHO International Standards for anti-SARS-CoV-2 immunoglobulin. The study involved 44 laboratories from 15 countries and the use of live and pseudotype-based neutralisation assays, ELISA, rapid tests, and other methods. The outcomes of the study were submitted to WHO in November, 2020. The inter-laboratory variation was reduced more than 50 times for neutralisation and 2000 times for ELISA when assay values were reported relative to the International Standard. The International Standard and International Reference Panel for anti-SARS-CoV-2 immunoglobulins were adopted by the WHO Expert Committee on Biological Standardization on Dec 10, 2020. 2 The International Standard allows the accurate calibration of assays to an arbitrary unit, thereby reducing inter-laboratory variation and creating a common language for reporting data. The International Standard is based on pooled human plasma from convalescent patients, which is lyophilised in ampoules, with an assigned unit of 250 international units (IU) per ampoule for neutralising activity. For binding assays, a unit of 1000 binding antibody units (BAU) per mL can be used to assist the comparison of assays detecting the same class of immunoglobulins with the same specificity (eg, anti-receptor-binding domain IgG, anti-N IgM, etc) The International Standard is available in the NIBSC catalogue. Initiatives have been launched for the harmonisation of immune response assessment across COVID-19 vaccine candidates, including the CEPI Global Centralised Laboratory Network. 3 CEPI centralised laboratories will achieve harmonisation of the results from different vaccine clinical trials with the use of common standard operating procedures and the same crucial reagents, including a working standard calibrated to the international standard. The basic tool for any harmonisation is the global use of an International Standard and IU to which assay data need to be calibrated with the use of a reliable method. It is therefore crucial that the International Standard is properly used by all vaccine developers, national reference laboratories, and academic groups worldwide, and that immunogenicity results are reported as an international standard unit (IU/mL for neutralising antibodies and BAU/mL for binding assay formats). In this manner, the results from clinical trials expressed in IU would allow for the comparison of the immune responses after natural infection and induced by various vaccine candidates. This comparison is particularly important for the identification of correlates of protection against COVID-19; should neutralising antibodies be further supported as a component of the protective response, the expression of antibody responses in IU/mL is essential to gather a consensus from several clinical trials and other studies on the titre required for protection. Although the correlate of protection against SARS-2-CoV has not yet been unequivocally defined, antibodies are likely to be at least part of the protective response. The effect of new variants on the evaluation of antibodies is obvious and unequivocal comparisons are required. Reporting the immunological responses from vaccine clinical trials against the International Standard is essential for the evaluation of clinical data submitted to national regulatory authorities as well as to WHO for emergency use listing, especially as placebo-controlled efficacy studies become operationally unfeasible. There will be a substantial effect on the use of the International Standard if regulatory authorities worldwide request data in IU/mL or BAU/mL. We also encourage journal editors and peer reviewers to ensure that the international standard is used as the benchmark in publications and that data from serology assays are reported in International Standard units. We declare no competing interests.

0 comments Cited 188 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Fabrizio Nelli:

ORCID: http://orcid.org/0000-0001-8374-1362

fabrizio.nelli@asl.vt.it

Journal

Journal ID (nlm-ta): Clin Exp Med

Journal ID (iso-abbrev): Clin Exp Med

Title: Clinical and Experimental Medicine

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1591-8890

ISSN (Electronic): 1591-9528

Publication date (Electronic): 20 January 2024

Publication date PMC-release: 20 January 2024

Publication date (Print): 2024

Volume: 24

Issue: 1

Electronic Location Identifier: 13

Affiliations

[1 ]Medical Oncology Unit, Department of Oncology and Hematology, Central Hospital of Belcolle, Strada Sammartinese Snc, 01100 Viterbo, Italy

[2 ]Biostatistics Unit, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, IRCCS, ( https://ror.org/00rg70c39) Rome, Italy

[3 ]Citofluorimetry Unit, Department of Oncology and Hematology, Central Hospital of Belcolle, Viterbo, Italy

[4 ]Infectious Disease Unit, Department of Medicine, Central Hospital of Belcolle, Viterbo, Italy

[5 ]Microbiology and Virology Unit, Department of Oncology and Hematology, Central Hospital of Belcolle, Viterbo, Italy

Author information

Fabrizio Nelli http://orcid.org/0000-0001-8374-1362

Article

Publisher ID: 1263

DOI: 10.1007/s10238-023-01263-2

PMC ID: 10799787

PubMed ID: 38244147

SO-VID: 0bb48ded-17c6-429e-8223-109a6e6928ac

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 7 October 2023

Date accepted : 7 December 2023

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: sars-cov-2,covid-19 vaccine,third dose,t cell,solid tumors,active treatment,herpes zoster

Data availability:

ScienceOpen disciplines: Medicine

Keywords: sars-cov-2, covid-19 vaccine, third dose, t cell, solid tumors, active treatment, herpes zoster

Herpes zoster after the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in actively treated cancer patients: a prospective study

Read this article at

Abstract

Supplementary Information

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 45

Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting

Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection

WHO International Standard for anti-SARS-CoV-2 immunoglobulin

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 163

Most referenced authors 696