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Summary Shift work can cause circadian misalignment, which often results in sleeping problems and has been associated with immune dysfunction. To better understand the impact of shift work on a primary immune response to vaccination, we compared severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)‐specific humoral and cellular immune responses after one injection of the messenger RNA (mRNA)‐1273 vaccine between day workers (n = 24) and night shift workers (n = 21). In addition, duration and quality of sleep were assessed for a period of 7 days around the time of vaccination using actigraphy and daily sleep diaries, and their relationship with immunogenicity of mRNA‐1273 vaccination was studied. We found that median total sleep time on the 2 days immediately after vaccination, which coincided with the days that night shift workers worked night shifts, was significantly lower in night shift workers (342 and 318 min) than day workers (431 and 415 min) (both p < 0.001). There was no difference in sleep quality between day workers and night shift workers. Furthermore, no difference in the antibody response between the two groups was observed, yet night shift workers had a significantly higher virus‐specific T‐cell response than day workers 28 days after immunisation (p = 0.013). Multivariate regression analysis showed no association between sleep duration, sleep quality and SARS‐CoV‐2‐specific humoral or cellular immune responses. Collectively, these findings indicate that shift work‐induced sleep loss and night shift work have little to no effect on the primary immune response to mRNA‐based COVID‐19 vaccination. [ABSTRACT FROM AUTHOR]

Measles is a highly contagious, vaccine-preventable anthroponotic infection. Despite the policy of active measles vaccination for entire global population, measles has not completely disappeared, it wanes and waxes in outbreaks. It has been shown that not only the unvaccinated but also the vaccinated, which is quite understandable, subjects are involved in measles progression. The study was aimed at assessing features of the immune response in adult measles patients at rise in disease incidence upon its eradication. 1.158 blood sera from measles patients aged 18 to 70 living in Moscow and the Moscow region were studied by ELISA (Euroimmun, Germany). The vast majority of subjects were aged 1840 years comprising 72.36% cases. 69 sera collected at a later timepoint (1020 days from rash onset) were excluded and analyzed separately. According to anti-measles IgG and avidity level, the data were stratified as follows: group 1 with a primary type of immune response 582 sera (53.44%), not vaccinated in childhood; group 2 (secondary response) 446 sera (40.96%), vaccinated in childhood, but lost anti-measles antibodies; group 3 with intermediate level of parameters 61 sera. To clarify the type of immune response in group 3, an additional analysis of the spectrum of anti-measles antibody subclasses was carried out. It was shown that a mixed type of response was detected in this group: 31 subjects mainly had primary immune response, and 30 subjects secondary immune response. At the same time, 40 out of 61 subjects were vaccinated against measles 13 months prior to disease onset, i.e., it was overlapped on arising post-vaccination immunity. Thus, the previously identified trend towards the loss of post-vaccination immunity among older schoolchildren and young adults vaccinated in childhood who are involved in the epidemic process continues to worsen.

After development in the thymus, naive T lymphocytes come into circulation and continuously recirculate between the blood and peripheral lymphoid organs for activation and transformation into effector cells. The movement of naive T lymphocytes represents an ordered sequence controlled by the expression of specific of specific proteins (selectin, integrin and chemokine) that includes the recruitment of circulating lymphocytes on the luminal surface of the blood vessel, transendothelial transition and migration within the extravascular compartment of peripheral lymphoid organs. The question of the movement of naive T lymphocytes in and out of non-lymphoid organs in physiological conditions has not been fully resolved. There is an opinion that naive T lymphocytes under physiological conditions routinely access almost all non-lymphoid organs for the purpose of immunosurveillance and/or tolerance induction. Non-lymphoid organs burdened by chronic inflammation and tumor processes may possess a significant number of naive T lymphocytes. Organized lymphoid tissue causally contributes to the persistence of certain autoimmune diseases. Recruitment in tumor tissue and subsequent antitumor immune response correspond with a positive prognosis.

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Introduction. The implementation of the WHO Measles Elimination Program has yielded serious results, but in recent years an increase in the incidence rate of this infection has been observed. In particular, according to the WHO, in 2019 vs. 2018 measles morbidity was elevated by 3-fold worldwide. While investigating measles outbreaks among patients, apart from unvaccinated subjects, a substantial group of adults vaccinated in childhood was distinguished. The aim of this work was to examine the characteristics of humoral measles immunity in adult measles patients as well as subjects after measles vaccination. Materials and methods. 50 adult measles patients aged 20 to 55 years were examined. In all patients, the diagnosis was confirmed clinically and by laboratory assays by detecting measles IgM antibodies. The second group consisted of 50 conditionally healthy seronegative age-matched adults, vaccinated with the live measles vaccine (Microgen, Russia). Peripheral blood samples were collected from the cubital vein in total volume of 4 ml on 6±1 day after the onset of rash in patients as well as 6 weeks after vaccination. Specific measles antibodies and their avidity were determined by ELISA using the commercial Avidity: Anti-Measles Viruses ELISA/IgG kit (Euroimmun, Germany). Results. It was shown that people aged 20—35 years more likely suffered from measles than elderly. And it was in this age group that healthy measles seronegative individuals were more abundant. Among vaccinees, 44% responded to vaccination with the primary type of immune response, and 56% responded with the secondary type, while among measles patients, 34% and 66% responded with the primary and secondary type, respectively, as follows from the spectrum of specific IgG subclasses and the antibody avidity assay. The secondary type of immune response indicates that these subjects were apparently vaccinated against measles in childhood, but lost with time long-lived plasma cells producing protective antibodies. While comparing the parameters of specific humoral immunity in groups with acute measles infection (day 6 from the onset of rash) and early convalescents (3 weeks after the onset of rash), it was shown that the level of specific IgG increased threefold in early convalescents (p < 0.01) compared with those at acute phase. The level of specific IgA, on the contrary, decreased from 73.44 (69—75.3) Me/ml to 48.64 (45—56.4) Me/ml, but remained very high. At the same time, the spectrum of specific IgG subclasses shifted from primary immune response (high IgG3 and low IgG1) to secondary response (low IgG3 and high IgG1), which is typical for the response of emerging memory B cells.

In 2010—2016, blood serum samples were examined from 5539 patients, aged < 1—60 years, with clinically and laboratory confirmed measles. Primary or secondary type of immune response was determined for all measles cases. Studies were performed with children aged < 1—14 years (2381), adolescents, 15—17 years old (189), and adults aged 18—60 years (2969). Serum measles-specific IgM antibodies were measured by “VektoKor’ IgM” ELISA test system (Russia), concentration and avidity of specific IgG — by using “Anti-Measles Viruses ELISA/IgG” and “Avidity: Anti-Measles Viruses ELISA/ IgG” (Euroimmun, Germany). Primary immune response was identified based on the presence of serum measles-specific low avidity IgM and IgG antibodies, whereas secondary immune response was characterized by detecting high avidity IgM and IgG antibodies at concentration of ≥ 5.0 IU/ml. Analyzing measles-specific IgM antibodies in 2010—2016 demonstrated that measles morbidity was mainly due to children, aged 1—2 years reaching up to 39.9% of the total number of children with measles aged < 1—14 years as well as adults aged 18—40 years old comprising as high as 80.1% total number of patients aged 15—60 years. Serum measles-specific IgG testing showed that in 15.0% of cases they were detected at concentration of ≥ 5.0 IU/ml. Further serum dilution resulted in finding IgG titer ranging within 8.5—45.0 IU/ml (21.4+0.36) and high avidity antibodies in 80—100% (92.5+0.2) cases. The remaining 85.0% cases found low avidity measles-specific IgG antibodies (< 30%) at concentration of 0.2—3.46 IU/ml (1.73+0.03). An age-related analysis of our data demonstrated that all children under 14 with laboratory-confirmed measles developed primary immune response. Moreover, in 73.7% of measles patients aged 15—60 with primary immune response measles might be prevented by timely vaccination, whereas persons with “vaccine failure” comprised 26.3%. In 2010 (0.09 per 100,000 subjects) and 2016 (0.12 per 100,000 subjects), frequency of patients with “vaccine failure” during relative epidemic well-being was 35.3% and 18.2%, respectively, exceeding 9.9% (p < 0.001) serving as a hallmark 2014 high measles incidence rate (3.24 per 100,000 subjects).The data obtained indicate that measles virus circulate among people with “vaccine failure,” which may account for potential to spread and infect unprotected population cohorts as well as cause measles outbreaks during periods of epidemic well-being.

MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8+ T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8+ T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8+ T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8+ T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8+ T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics.

Germinal centers (GCs) are transient structures in the secondary lymphoid organs, where B cells undergo affinity maturation to produce high affinity memory and plasma cells. The lifetime of GC responses is a critical factor limiting the extent of affinity maturation and efficiency of antibody responses. While the average lifetime of overall GC reactions in a lymphoid organ is determined experimentally, the lifetime of individual GCs has not been monitored due to technical difficulties in longitudinal analysis. In silico analysis of the contraction phase of GC responses towards primary immunization with sheep red blood cells suggested that if individual GCs had similar lifetimes, the data would be consistent only when new GCs were formed until a very late phase after immunization. Alternatively, there could be a large variation in the lifetime of individual GCs suggesting that both long and short-lived GCs might exist in the same lymphoid organ. Simulations predicted that such differences in the lifetime of GCs could arise due to variations in antigen availability and founder cell composition. These findings identify the potential factors limiting GC lifetime and contribute to an understanding of overall GC responses from the perspective of individual GCs in a primary immune response.

Summary MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8 + T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8 + T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8 + T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8 + T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8 + T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics. [ABSTRACT FROM AUTHOR]

The proliferation of specific lymphocytes is the central tenet of the clonal selection paradigm. Antigen recognition by T cells triggers a series of events that produces expanded clones of differentiated effector cells. TCR signaling events are detectable within seconds and minutes and are likely to continue for hours and days in vivo. Here, I review the work done on the importance of TCR signals in the later part of the expansion phase of the primary T cell response, primarily regarding the regulation of the cell cycle in CD4+ and CD8+ cells. The results suggest a degree of programming by early signals for effector differentiation, particularly in the CD8+ T cell compartment, with optimal expansion supported by persistent antigen presentation later on. Differences to CD4+ T cell expansion and new avenues towards a molecular understanding of cell cycle regulation in lymphocytes are discussed.

The proliferation of specific lymphocytes is the central tenet of the clonal selection paradigm. Antigen recognition by T cells triggers a series of events that produces expanded clones of differentiated effector cells. TCR signaling events are detectable within seconds and minutes and are likely to continue for hours and days in vivo. Here, I review the work done on the importance of TCR signals in the later part of the expansion phase of the primary T cell response, primarily regarding the regulation of the cell cycle in CD4+ and CD8+ cells. The results suggest a degree of programing by early signals for effector differentiation, particularly in the CD8+ T cell compartment, with optimal expansion supported by persistent antigen presentation later on. Differences to CD4+ T cell expansion and new avenues toward a molecular understanding of cell cycle regulation in lymphocytes are discussed. [ABSTRACT FROM AUTHOR]