Opposite Effects of mRNA-Based and Adenovirus-Vectored SARS-CoV-2 Vaccines on Regulatory T Cells: A Pilot Study

Francesca La Gualana; Francesca Maiorca; Ramona Marrapodi; Francesca Villani; Marzia Miglionico; Stefano Angelo Santini; Fabio Pulcinelli; Laura Gragnani; Silvia Piconese; Massimo Fiorilli; Stefania Basili; Milvia Casato; Lucia Stefanini; Marcella Visentini

doi:10.3390/biomedicines11020511

Opposite Effects of mRNA-Based and Adenovirus-Vectored SARS-CoV-2 Vaccines on Regulatory T Cells: A Pilot Study

Biomedicines. 2023 Feb 10;11(2):511. doi: 10.3390/biomedicines11020511.

Authors

Affiliations

¹ Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
² Department of Basic, Clinical, Intensive and Perioperative Biotechnological Sciences, Catholic University, Largo Agostino Gemelli 8, 00168 Rome, Italy.
³ Synlab Italia, Via Martiri delle Foibe 1, 20900 Monza, Italy.
⁴ Department of Experimental Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
⁵ MASVE Interdepartmental Center, Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
⁶ Department of Internal Clinical Sciences, Anaesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.

Abstract

New-generation mRNA and adenovirus vectored vaccines against SARS-CoV-2 spike protein are endowed with immunogenic, inflammatory and immunomodulatory properties. Recently, BioNTech developed a noninflammatory tolerogenic mRNA vaccine (MOGm1Ψ) that induces in mice robust expansion of antigen-specific regulatory T (Treg) cells. The Pfizer/BioNTech BNT162b2 mRNA vaccine against SARS-CoV-2 is identical to MOGm1Ψ except for the lipid carrier, which differs for containing lipid nanoparticles rather than lipoplex. Here we report that vaccination with BNT162b2 led to an increase in the frequency and absolute count of CD4^posCD25^highCD127^low putative Treg cells; in sharp contrast, vaccination with the adenovirus-vectored ChAdOx1 nCoV-19 vaccine led to a significant decrease of CD4^posCD25^high cells. This pilot study is very preliminary, suffers from important limitations and, frustratingly, very hardly can be refined in Italy because of the >90% vaccination coverage. Thus, the provocative perspective that BNT162b2 and MOGm1Ψ may share the capacity to promote expansion of Treg cells deserves confirmatory studies in other settings.

Keywords: SARS-CoV-2; Treg; immunogenicity; regulatory T-cells; tolerance; vaccines.

Abstract

Grants and funding