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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02695

Pneumococcal polysaccharide vaccine ameliorates murine lupus

 Chiara Cantarelli1, 2, Chiara Guglielmo1, 3,  Susan Hartzell1,  Fadi E. Salem1, Sofia Andrighetto1, Victor P. Gazidova4, Enrico Fiaccadori2,  Gaetano La Manna3,  Gianluigi Zaza5,  Jeremy Leventhal1,  Ioannis Tassiulas1 and  Paolo Cravedi1*
  • 1Icahn School of Medicine at Mount Sinai, United States
  • 2University Hospital of Parma, Italy
  • 3University of Bologna, Italy
  • 4Maimonides Medical Center, United States
  • 5University of Verona, Italy

Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL-lpr mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology, and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (TFH) and T follicular regulatory cells (TFR), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice.
In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL-lpr mice, which associates with fewer TFH and increased TFR. Together, the data support the use of Prevnar vaccination in individuals with SLE.

Keywords: lupus, Prevnar, Vaccination, TFH, TfR

Received: 17 Sep 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 Cantarelli, Guglielmo, Hartzell, Salem, Andrighetto, Gazidova, Fiaccadori, La Manna, Zaza, Leventhal, Tassiulas and Cravedi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Paolo Cravedi, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, United States, paolo.cravedi@mssm.edu