Assessing the long-stand antibody response induced by COVID-19 vaccines: A study in an educational cohort in San Luis, Argentina.

BACKGROUND: Although there has developed an increased interest in the vaccines BNT1622b2 (Pfizer/BioNTech), mRNA-1273 (Moderna/NIAID), and ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford), there are still few reports describing the immune response induced by different vaccine platforms in real-world settings of low-income countries. Here, we proposed to analyse the humoral immune response elicited by the primary vaccines used in Argentina from July-December 2021. METHODS: Anti-SARS-CoV-2-Spike-RBD IgG and neutralising antibodies were assayed by ELISA in a total of 871 serum samples obtained from 376 volunteers from an educational staff. The individuals were vaccinated with BBIBP-CorV (Sinopharm), ChAdOx1 nCoV-19 (AstraZeneca/University of Oxford, AZ), Gam-COVID-Vac (Sputnik V, SpV) or combined vaccines (mostly SpV and mRNA-1273, Moderna). The antibody response was analysed several days after the initial vaccination (20, 40, 120 and 180 days). RESULTS: After receiving at least one dose of the COVID-19 vaccine, we detected 93.34% of seroprevalence. Previously SARS-CoV-2 infected showed higher antibody concentrations compared with naïve vaccinees. Six months after the initial vaccination, combined vaccination induced higher anti-SARS-CoV-2 antibody levels than the other vaccines in naïve volunteers. However, we did not find differences in the neutralising responses after any vaccine from naïve vaccines or between the naïve and previously infected volunteers on day 120 after vaccination. CONCLUSIONS: Our long-term analysis of volunteers from the educational system provides data in a real-world context, showing the benefits of a boost dose still in previously infected volunteers, and suggesting the advantages of a heterologous prime-boost schedule.

IL-12/23p40 overproduction by dendritic cells leads to an increased Th1 and Th17 polarization in a model of Yersinia enterocolitica-induced reactive arthritis in TNFRp55-/- mice.

Dendritic cells (DCs) play critical functions in the initiation of immune responses. Understanding their role in reactive arthritis (ReA) will help delineate the pathogenesis of this arthropathy. In early studies, we detected IL-12/23p40 deregulation in Yersinia entercolitica (Ye)-induced ReA in TNFRp55-deficient (TNFRp55-/-) mice. In this study, we assessed the contribution of DCs in this overproduction. First, greater levels of IL-12/23p40, IFN-γand IL-17A were confirmed in supernatants of lipopolysaccharide (LPS)-stimulated TNFRp55-/-splenocytes obtained on arthritis onset (day 14 after Ye infection). Later, DCs were identified as a precise source of IL-12/23p40 since increased frequency of splenic IL-12/23p40+DCs was detected in TNFRp55-/- mice. After robust in vivo amplification of DCs by injection of Fms-like tyrosine kinase 3-Ligand (Flt3L)-transfected BL16 melanoma, DCs were purified. These cells recapitulated the higher production of IL-12/23p40 under TNFRp55deficiency. In agreement with these results, TNFRp55-/- DCs promoted Th1 and Th17 programs by co-culture with WT CD4+lymphocytes. A mechanistic study demonstrated that JNK and p38 MAPK pathways are involved in IL-12/23p40 overproduction in purified TNFRp55-/- DCs as well as in the JAWS II cell line. This deregulation was once again attributed to TNFRp55 deficiency since CAY10500, a specific inhibitor of this pathway, compromised TNF-mediated IL-12/23p40 control in LPS-stimulated WT DCs. Simultaneously, this inhibition reduced IL-10 production, suggesting its role mediating IL-12/23p40 regulation by TNFRp55 pathway. These results provide experimental data on the existence of a TNFRp55-mediated anti-inflammatory circuit in DCs. Moreover, these cells may be considered as a novel target in the treatment of ReA.