SARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina. Seroconversion rates in unexposed subjects after the first and second doses were 40% and 100%, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 ( p < 0.0001). The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model ( p = 0.005). A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses ( p = 0.008). Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed ( p < 0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine ( p < 0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects. Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels. Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.

SUMMARYThe ability of peripheral blood mononuclear cells (PBMC) from patients with active tuberculosis to display cytotoxic responses against autologous Mycobacterium tuberculosis ( Mtb )-pulsed macrophages was evaluated. Non-MHC restricted cell-dependent lytic activity was observed in ex vivo effector cells from tuberculosis patients and was mediated mainly by CD3 + gd TCR + T ( gd T) cells bearing CD56 and/ or CD16 molecules. MHC-restricted and non-MHC restricted cytotoxic T cells (CTL) were differentially expanded upon stimulation with Mtb in tuberculosis patients and normal controls (N). Class-I restricted CD8 + CTL and class-II restricted CD4 + CTL were generated in PPD + N and to a lesser extent in PPD -N. Mtb -stimulated effector cells from tuberculosis patients became progressively non-MHC restricted CD4 -CD8 -gd T cells, while lytic activity of CD4 + and CD8 + CTL decreased gradually as the disease became more severe. On the other hand, target cells were lysed by ex vivo cells from tuberculosis patients through the Fas-FasL and perforin pathways. Mtb -induced CD4 + CTL from tuberculosis patients and N controls preferentially employed the Fas-FasL mechanism. Mtb -induced CD8 + CTL effector cells from patients used the perforin-based mechanism while cells from N controls also used the Fas-FasL pathway. While Mtb -induced gd CTL from patients and PPD -N employed the latter mechanism cells from PPD + N individuals also used the perforin pathway. It can be concluded that shifts in the CTL response and the cytolytic mechanisms take place as the pulmonary involvement becomes more severe.

SummaryInterleukin 9 (IL-9) is a T-cell derived factor preferentially expressed by CD4+ Th2 cells and it has been characterized both in human and murine systems. It is a pleiotropic cytokine with multiple functions on cells of the lymphoid, myeloid and mast cell lineages, as well as on lung epithelial cells. Other activities described for IL-9 support its contribution to asthma and its important role in helminthic infections, where a Th2 response can be protective and IL-9 enhances resistance or is responsible for elimination of the nematode. Nevertheless, until recently there were no studies on its role in bacterial infections in man. We have demonstrated that cytokines can modulate the specific cytotoxicity generation in peripheral blood mononuclear cells from leprosy patients and normal controls. In the present report we studied the effect of IL-9 in this experimental model. Our results indicate that IL-9 can counteract the negative effect mediated by IL-4 on the generation of M. leprae-induced cytotoxic T lymphocytes. Moreover, it can increase this lytic activity in controls and enhance the stimulatory effect of IL-2 or IL-6 in cells from leprosy patients and controls. IL-9 is also able to revert the inhibitory effect of IL-10 and IL-13 on the M. leprae-induced cytotoxic activity. Although the exact mechanism of action of IL-9 remains to be determined, interferon gamma seems to be required for the effect of IL-9 in this experimental model. These data suggest that IL-9 may have an atypical Th2 behaviour and play a role in the modulation of the immune response to mycobacterial infections.

Atopic asthma results from airway inflammation triggered by an environmental allergen. Symptoms include wheezing, dyspnea and cough, airway narrowing and/or hyperresponsiveness to several inhaled stimuli. Inflammation develops in a two-phase fashion. The first phase after exposure to the allergen consists of degranulation and release of both histamine and other stored preformed inflammatory mediators as well as newly synthesized ones, including cytokines, all of which increase mucus secretion and smooth muscle contraction. The second phase occurs later and lasts longer; it is due to different molecules: several cytokines and chemokines, arachidonic acid derivatives, enzymes such as metalloproteinases and cell adhesion molecules. Cytokines are key players in the chronic inflammation in asthma patients, but details on their role and interactions still remain undetermined. Recent evidence suggests that allergic asthma is a multifaceted condition actively controlled by effector as well as regulatory T cells (Tregs). T helper (Th) 2 cells and Th17 cells increase airway inflammation, while Tregs are anti- inflammatory. Cytokines are involved in the development and activation of all T cell subpopulations. They are also involved directly or indirectly in most approaches to asthma treatment. Several cytokines have been tested as therapeutic targets and some of the currently used therapies like corticosteroids, beta agonists and allergen immunotherapy affect cytokine production. The increased knowledge on cytokine interplay and lymphocyte subsets should generate new therapeutic strategies in the near future.