Dynamics of SARS-CoV-2 antibodies after natural infection: insights from a study on Pasteur Institute of Tunis employees.

This study aimed to assess the kinetics of antibodies against the SARS-CoV-2, following natural infection in a cohort of employees of the Institut Pasteur de Tunis (IPT) and to assess the risk of reinfection over a 12-months follow-up period. A prospective study was conducted among an open cohort of IPT employees with confirmed SARS-CoV-2 infection that were recruited between September 2020 and March 2021. Sera samples were taken at 1, 3, 6, 9 and 12 months after confirmation of COVID-19 infection and tested for SARS-CoV-2-specific immunoglobulin G (IgG) antibodies to the spike (S-RBD) protein (IgG anti-S-RBD) and for neutralizing antibodies. Participants who had an initial decline of IgG anti-S-RBD and neutralizing antibodies followed by a subsequent rise in antibody titers as well as those who tested positive for SARS-CoV-2 by RT-PCR after at least 60 days of follow up were considered as reinfected. In total, 137 individuals were included with a mean age of 44.7 ± 12.3 years and a sex-ratio (Male/Female) of 0.33. Nearly all participants (92.7%) were symptomatic, and 2.2% required hospitalization. Among the 70 participants with three or more prospective blood samples, 32.8% were reinfected among whom 11 (47.8%) reported COVID-19 like symptoms. Up to 12 months of follow up, 100% and 42.9% of participants had detectable IgG anti-S-RBD and neutralizing antibodies, respectively. This study showed that humoral immune response following COVID-19 infection may persist up to 12 months after infection despite the potential risk for reinfection that is mainly explained by the emergence of new variants.

PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes.

BACKGROUND: The saliva of sand flies, vectors of Leishmania parasites, contains several components that exert pharmacological activity facilitating the acquisition of blood by the insect and contributing to the establishment of infection. Previously, we demonstrated that PpSP32 is the immunodominant salivary antigen in humans exposed to Phlebotomus papatasi bites and validated its usefulness as a predictive biomarker of disease. PpSP32, whose functions are little known to date, is an intriguing protein due to its involvement in the etiopathogenesis of pemphigus, an auto-immune disease. Herein, we aimed to better decipher its role through the screening of several immunomodulatory activity either on lymphocytes or on monocytes/macrophages. METHODS: Peripheral mononuclear cells from healthy volunteers were stimulated with anti-CD3/anti-CD28 antibodies, phytohemagglutinin, phorbol 12-myristate 13-acetate/ionomycin, or lipopolysaccharide in the presence of increasing doses of PpSP32. Cell proliferation was measured after the addition of tritiated thymidine. Monocyte activation was tested by analyzing the expression of CD86 and HLA-DR molecules by flow cytometry. Cytokine production was analyzed in culture supernatants by ELISA. THP-1-derived macrophages were stimulated with LPS in the presence of increasing doses of PpSP32, and cytokine production was analyzed in culture supernatants by ELISA and multiplex technique. The effect of PpSP32 on NF-kB signaling was tested by Western blot. The anti-inflammatory activity of PpSP32 was assessed in vivo in an experimental inflammatory model of carrageenan-induced paw edema in rats. RESULTS: Our data showed that PpSP32 down-modulated the expression of activation markers in LPS-stimulated monocytes and THP1-derived macrophages. This protein negatively modulated the secretion of Th1 and Th2 cytokines by human lymphocytes as well as pro-inflammatory cytokines by monocytes, and THP1-derived macrophages. PpSP32 treatment led to a dose-dependent reduction of IκB phosphorylation. When PpSP32 was injected into the paw of carrageenan-injected rats, edema was significantly reduced. CONCLUSIONS: Our data indicates that PpSP32 induces a potent immunomodulatory effect on monocytes and THP-1-derived macrophages. This inhibition could be mediated, among others, by the modulation of the NF-kB signaling pathway. The anti-inflammatory activity of PpSP32 was confirmed in vivo in the carrageenan-induced paw edema model in rats.