The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5 CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and CD4 T-cell loss are recognized features of HIV infection , in the present study, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HCs), and these cells displayed a central memory phenotype. Sixteen patients and 8 HCs in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responders (n 8) and HCs, pTFH cells underwent expansion with increased IL-21 and CXCL13 secretion in H1N1-stimulated PBMC culture supernatants at week 4 (T2). These changes were not seen in vaccine nonre-sponders (n 8). In coculture experiments , sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH were correlated with memory B cells, serum H1N1 Ab titers, and Ag-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight into cellular determinants of vaccine-induced Ab response, which may have relevance for vaccine design. (Blood. 2012;120(5):985-993)
Mechanisms underlying failure of novel 2009 H1N1 influenza vaccine-induced Ab responses in HIV-infected persons are poorly understood. This study prospectively evaluated 16 HIV-infected patients on combination antiretroviral therapy and eight healthy controls (HC) who received a single 15 μg dose of nonadjuvanted novel 2009 H1N1 influenza vaccine during the 2009 H1N1 epidemic. Peripheral blood was collected at baseline (T0) and at 7 d (T1) and 28 d (T2) postvaccination for evaluation of immune responses. Prevaccination hemagglutination inhibition Ab titer was <1:20 in all except one study participant. At T2, all HC and 8 out of 16 patients (50%) developed a vaccine-induced Ab titer of ≥1:40. Vaccine responder (R) and vaccine nonresponder patients were comparable at T0 in age, CD4 counts, virus load, and B cell immunophenotypic characteristics. At T2, HC and R patients developed an expansion of phenotypic and functional memory B cells and ex vivo H1N1-stimulated IgG Ab-secreting cells in an ELISPOT assay. The memory B cell response was preceded by a significant expansion of plasmablasts and spontaneous H1N1-specific Ab-secreting cells at T1. At T2, HC and R patients also exhibited significant increases in serum IL-21 levels and in the frequency and mean fluorescence intensity of IL-21R–expressing B cells, which correlated with serum H1N1 Ab titers. Vaccine nonresponder patients failed to develop the above-described vaccine-induced immunologic responses. The novel association of novel 2009 H1N1 vaccine-induced Ab responses with IL-21/IL-21R upregulation and with development of memory B cells and plasmablasts has implications for future research in vaccine design.
Highlights
Healthcare personnel are at risk for nosocomial acquisition of COVID-19.
We evaluated the exposure history of hospital personnel with COVID-19.
Twenty-five percent of personnel with COVID-19 were exposed to an infected patient or co-worker.
Exposure to infected co-workers occurred in nonpatient care settings.
Fourteen percent of personnel with COVID-19 were exposed in the community.
The prevalence of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM 2) is decreasing in developed countries despite the increase in the percentage of subjects with obesity and other well-recognized cardiovascular risk factors. In contrast, the recent transition of the economic model experienced by developing countries, characterized by the adoption of a Western lifestyle, that we have named "socioeconomic pathology," has led to an increase in the burden of CVD. It has been demonstrated that conventional cardiovascular risk factors in developed and developing countries are the same. Why then does the population of developing countries currently have a higher incidence of CVD than that of developed countries if they share the same risk factors? We have proposed the existence of a higher susceptibility to the development of systemic inflammation at low levels of abdominal obesity in the population of developing countries and the consequent endothelial dysfunction, insulin resistance, DM 2, and CVD. In contrast, an important percentage of obese people living in developed countries have a healthy phenotype and low risk of developing CVD and DM 2. Human epidemiologic studies and experimental dietary interventions in animal models have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances early in life may later have a persistent effect on an adult's health that may even be transmitted to the next generations. Epigenetic changes dependent on nutrition could be key in this evolutionary health behavior, acting as a buffering system, permitting the adaptation to environmental conditions by silencing or increasing the expression of certain genes.
Background
Mechanisms underlying failure of influenza vaccine-induced antibody responses in HIV-infected persons are poorly understood.
Objective
To investigate innate immune factors regulating B cell function in HIV infected persons and to correlate them with serologic responses to H1N1/09 vaccine.
Methods
We evaluated immunologic characteristics of 17 HIV-infected patients and eight healthy controls (HC) at 0, 7 and 28 days (designated T0, T1 and T2) following a single 15 mcg dose of non-adjuvanted H1N1/09 influenza vaccine using Flow cytometry, ELISPOT and ELISA assays. All HC and nine patients (53%) seroconverted with >1:40 hemagglutination inhibition antibody titer at T2.
Results
In vaccine responders (R) and HC, serum levels of BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand) increased from T0 to T2 in conjunction with increases in frequencies of memory B cells. Concurrently, receptors for these factors showed changes, with increases in expression of TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) and decreases in BAFF receptor in memory B cells. IL-2 secreting cells and IgG antibody secreting cells increased at T2 in R and HC in ex-vivo H1N1 antigen stimulated cultures. These immunologic responses were not evident at T1 and were deficient in vaccine non-responder patients at T2. At T0, vaccine non-responders had lower frequencies of BAFF-R and TACI expressing memory B cells than responders.
Conclusion
Impaired memory B cell responses, deficiencies in serum BAFF and APRIL and alterations in their receptors on B cells were associated with failure of H1N1/09 influenza vaccine responses among virologically controlled HIV-infected patients.
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