Humoral immunoresponse elicited against an adenoviral-based SARS-CoV-2 coronavirus vaccine in elderly patients.

The early sequencing of the SARS-CoV-2 viral genome allowed for a speedy development of effective vaccines against the virus. Nevertheless, age-related immunosenescence, the inability to mount strong immune responses, still represents a major obstacle. Here, in a group of 149 elderly volunteers (70-96 years old), evolution of the humoral immune response over time to Gam-COVID-Vac (Sputnik V), a vaccine based on heterologous recombinant adenovirus-26 (Ad26) and adenovirus-5 (Ad5) carrying the Spike genome, was analyzed by an anti-RBD ELISA. At 28 days post vaccination (dpv), a seroconversion rate of 91% was achieved, showing the importance of administering at least two doses of Gam-COVID-Vac to elicit a robust immune response, especially in elderly individuals without previous SARS-CoV-2 infection. Interestingly, IgG specific antibodies that reached their highest titers around 28 dpv (median = 740), persisted without significant decrease after 60 dpv (median = 650). After 90 dpv, IgG titers began to drop, and at 180 dpv only 44.7% of the elderly individuals remained with detectable anti-RBD IgG antibodies. No significant differences were observed in specific humoral immune responses between genders at early times point. However, at 60 dpv anti-RBD titers were more persistent in elderly females, and only dropped at 90 dpv (p < 0.0001). As expected, the highest antibodies titers were elicited in the youngest subgroup (70-74 years). Our results show that Gam-COVID-Vac was able to deal with the ageing of the immune system, eliciting a robust immune response in an elderly cohort, which lasted approximately 90 dpv at high levels, and protected against COVID-19.

Tuberculosis resistente a medicamentos de primera línea en pacientes del cantón Durán, Ecuador / First-line drug-resistant tuberculosis in patients from the city of Duran, Ecuador

La tuberculosis continúa siendo un problema de salud pública. Al respecto, se realizó un estudio no experimental de corte transversal, con el objetivo de caracterizar clínica y epidemiológica-mente el estado de la TB resistente a medicamentos de primera línea en la ciudad de Durán, desde enero 2015 hasta diciembre 2019. Los datos incluidos en los documentos de la matriz del programa de tuberculosis resistente. De 1111 casos nuevos de tuberculosis reportados en el cantón Durán durante el período estudiado, 45 de estos presentaron resistencia a medicamentos de primera línea. El 88,89% tuvo resistencia a rifampicina, el 33,33% de los pacientes se dispen-sarizaron en 2019. Los valores de chi cuadrado de Pearson no mostraron asociación estadística-mente significativa entre las variables investigadas (p>0,05). Entre los involucrados predominó el grupo de edades de 20 a 39 años, el sexo masculino, la tuberculosis pulmonar, infectados con VIH/sida, resistencia clasificada como primaria, los que abandonaron el seguimiento al trata-miento y la no manifestación de reacciones adversas a los medicamentos. No se observó mortali-dad entre los casos nuevos, predominando entre aquellos con recaída, el género masculino y los que tuvieron tuberculosis extrapulmonar.

Tuberculosis is a disease that continues to be a public health problem. In this regard, a non-expe-rimental cross-sectional study was carried out to characterize clinically and epidemiologically the status of TB resistant to first-line drugs in the city of Durán, from January 2015 to December 2019. The data included in the resistant tuberculosis program matrix documents. 1111 new cases of tuberculosis were reported in the Duran canton during the study period, 45 of these ones presented resistance to first-line drugs. 88.89% had rifampicin resistance, 33.33% of the patients were dispensed in 2019. Pearson's chi-square values did not show a statistically significant asso-ciation between the investigated variables (p> 0.05). Among the study population, it was predo-minated the age group between 20 and 39, male sex, pulmonary tuberculosis, infected with HIV / AIDS, resistance classified as primary, those who abandoned the follow-up to treatment and the non-manifestation of adverse drug reactions. No mortality was observed among new cases, predominantly among those ones with relapse, the male gender and those ones who had extra-pulmonary tuberculosis

Long-term analysis of antibodies elicited by SPUTNIK V: A prospective cohort study in Tucumán, Argentina.

BACKGROUND: Gam-COVID-Vac (SPUTNIK V) has been granted emergency use authorization in 70 nations and has been administered to millions worldwide. However, there are very few peer-reviewed studies describing its effects. Independent reports regarding safety and effectiveness could accelerate the final approval by the WHO. We aimed to study the long-term humoral immune response in naïve and previously infected volunteers who received SPUTNIK V. METHODS: Humoral immune responses, assayed by anti-SARS-CoV-2-spike-RBD IgG ELISA and neutralization assays, were measured in 602 healthcare workers at 0, 14, 28, 60 and 180 days after receiving SPUTNIK V between December 2020 and July 2021 in Tucumán, Argentina. FINDINGS: Seroconversion was detected in 97% of individuals after 28 days post-vaccination (dpv) (N = 405). Anti-RBD titers began to decrease after 60 dpv (N = 328), but remained detectable in 94% at 90 dpv (N = 224). At 180 dpv, anti-RDB titers persisted in 31% (N = 146). Previous infection triggered an increased immune response to the first dose and increased neutralization activity against variants of concern (VOC). Second doses in previously infected individuals further increased titers, even 90 dpv (N = 75). Basal antibody titers had more influence on post-vaccination anti-RBD responses than the time elapsed between diagnosis and vaccination (N = 274). INTERPRETATION: Data presented herein provides essential knowledge regarding the kinetics of antibodies induced by SPUTNIK V up to six months after immunization, and suggests that when considering one-dose vaccination policies for individuals with previous SARS-CoV-2 infection, serological studies to determine basal titers may be important, independent of when diagnosis occurred. FUNDING: Tucumán Public Health System (SIPROSA), Argentinean National Research Council (CONICET), National University of Tucumán (UNT).

Beneficial Effects of Probiotic Consumption on the Immune System.

BACKGROUND: The gastrointestinal tract is one of the most microbiologically active ecosystems that plays a crucial role in the working of the mucosal immune system (MIS). In this ecosystem, the consumed probiotics stimulate the immune system and induce a network of signals mediated by the whole bacteria or their cell wall structure. This review is aimed at describing the immunological mechanisms of probiotics and their beneficial effects on the host. SUMMARY: Once administered, oral probiotic bacteria interact with the intestinal epithelial cells (IECs) or immune cells associated with the lamina propria, through Toll-like receptors, and induce the production of different cytokines or chemokines. Macrophage chemoattractant protein 1, produced by the IECs, sends signals to other immune cells leading to the activation of the MIS, characterized by an increase in immunoglobulin A+ cells of the intestine, bronchus and mammary glands, and the activation of T cells. Specifically, probiotics activate regulatory T cells that release IL-10. Interestingly, probiotics reinforce the intestinal barrier by an increase of the mucins, the tight junction proteins and the Goblet and Paneth cells. Another proposed mechanism of probiotics is the modulation of intestinal microbiota by maintaining the balance and suppressing the growth of potential pathogenic bacteria in the gut. Furthermore, it has been demonstrated that long-term probiotics consumption does not affect the intestinal homeostasis. The viability of probiotics is crucial in the interaction with IECs and macrophages favoring, mainly, the innate immune response. Macrophages and Dendritic cells (DCs) play an important role in this immune response without inducing an inflammatory pattern, just a slight increase in the cellularity of the lamina propria. Besides, as part of the machinery that probiotics activate to protect against different pathogens, an increase in the microbicidal activity of peritoneal and spleen macrophages has been reported. In malnutrition models, such as undernourishment and obesity, probiotic was able to increase the intestinal and systemic immune response. Furthermore, probiotics contribute to recover the histology of both the intestine and the thymus damaged in these conditions. Probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. Different mechanisms such as the generation of cytokines from activated pro-T-helper type 1, which favor the production of IgG instead of IgE, have been proposed. Key Messages: Probiotic bacteria, their cell walls or probiotic fermented milk have significant effects on the functionality of the mucosal and systemic immune systems through the activation of multiple immune mechanisms.

Probiotic fermented milk consumption modulates the allergic process induced by ovoalbumin in mice.

Orally administered probiotic micro-organisms are able to regulate the exacerbated immune response during the antigenic sensitisation process. The aim of the present study was to evaluate the potential efficacy of probiotic fermented milk (PFM) in preventing or treating allergy in an experimental model, and to investigate its underlying mechanisms. Ovoalbumin (OVA)-sensitised BALB/c mice were fed with PFM before the sensitisation procedure or fed continuously with PFM. At 7 and 15 d post-sensitisation, anti-OVA-specific IgE, IgG, IgG1 and IgG2a concentrations were measured in the serum and broncho-alveolar lavage fluid (BALF). Concentrations of interferon-γ (IFN-γ), IL-4, IL-10 and total secretory IgA (S-IgA) were measured in the supernatants of macerated lungs or in the BALF. The levels of IgA+, CD4+ and CD8+ T lymphocytes and F4/80+ cells were measured in the lungs by immunofluorescence. Inducible CD4+/CD25/Foxp3+ regulatory T (Treg) cells were evaluated in the lungs. PFM shifted the T helper (Th)2 profile response towards a Th1 response that led to the production of IgG instead of IgE, with increasing levels of IL-10 and IFN-γ that play an important role in immunomodulation exerted by PFM administration in sensitised mice. Anti-OVA-specific IgE levels were significantly decreased; however, there was no modification in the levels of anti-OVA-specific IgG and total S-IgA. PFM did not influence Treg cells in treated mice. Consumption of PFM could be a promising strategy in the amelioration of airway allergies, considering that the effect is mediated by the production of IgG through the activation of Th1 instead of the direct activation of Th2 cells to produce IgE.

Study of the effect exerted by fructo-oligosaccharides from yacon (Smallanthus sonchifolius) root flour in an intestinal infection model with Salmonella Typhimurium.

Beneficial effects of prebiotics like inulin and fructo-oligosaccharides (FOS) have been proven in health and nutrition. Yacon (Smallanthus sonchifolius), an Andean crop, contains FOS (50­70% of its dry weight) and, therefore, is considered a prebiotic. Commercial FOS can upregulate total secretory IgA (S-IgA) in infant mice, prevent infection with Salmonella in swine or enhance immune response for Salmonella vaccine in a mouse model. Previously, we found that administration of yacon root flour regulates gut microbiota balance and has immunomodulatory effects without inflammatory responses. The aim of the present paper is to analyse if yacon prevents enteric infection caused by a strain of Salmonella enteritidis serovar Typhimurium (S. Typhimurium) in a mouse model. BALB/c mice were supplemented with yacon flour (45 d), challenged with S. Typhimurium and killed to study pathogen translocation, total and specific IgA production by ELISA, presence of IgA and other cytokines and Toll-like receptor 4 (TLR4) and clustor of differentiation 206 (CD206) receptors positive cells by immunofluorescence and histological changes. Yacon flour administration had a protective effect from 15 to 30 d of treatment. We found a peak of total S-IgA production without translocation of the pathogen for these periods. At 30 d, there was an increase in IL-6 and macrophage inflammatory proteins-1aþ cells and expression of the receptors CD206 and TLR4. Yacon flour did not have incidence in pathogen-specific S-IgA production. Longer periods (45 d) of administration had no protective effect. Therefore, yacon can prevent enteric infection caused by S. Typhimurium when given up to 30 d; this effect would be mediated by enhancing non-specific immunity, such as total S-IgA, that improves the immunological intestinal barrier.