Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults

BACKGROUND: Untreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. METHODS: A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. RESULTS: Overall 64 participants were recruited - 20 HIV uninfected (HIV-), 30 HIV infected ART naïve (HIV+N) and 14 HIV-infected ART treated (HIV+T). ART treatment had been taken for a median of 33 months (Range 12-60 months). Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008); reduced memory B cells (27 vs. 51 cells/μl p = 0.0008). The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02). In the HIV+N group we did not find an association between CD4 count and B cell numbers. CONCLUSIONS: HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study

St. Patrick’s Day 2015 geomagnetic storm analysis based on Real Time Ionosphere Monitoring

A detailed analysis is presented for the days in March, 2015 surrounding St. Patrick’s Day 2015 geomagnetic storm, based on the existing real-time and near real-time ionospheric models (global or regional) within the group, which are mainly based on Global Navigation Satellite Systems (GNSS) and ionosonde data. For this purpose, a variety of ionospheric parameters is considered, including Total Electron Content (TEC), F2 layer critical frequency (foF2), F2 layer peak (hmF2), bottomside halfthickness (B0) and ionospheric disturbance W-index. Also, ionospheric high-frequency perturbations such as Travelling Ionospheric Disturbances (TIDs), scintillations and the impact of solar flares facing the Earth will be presented to derive a clear picture of the ionospheric dynamicsPostprint (published version

MIG and the Regulatory Cytokines IL-10 and TGF-β1 Correlate with Malaria Vaccine Immunogenicity and Efficacy

Malaria remains one of the world's greatest killers and a vaccine is urgently required. There are no established correlates of protection against malaria either for natural immunity to the disease or for immunity conferred by candidate malaria vaccines. The RTS,S/AS02A vaccine offers significant partial efficacy against malaria

Ionospheric scintillation monitoring and modelling

This paper presents a review of the ionospheric scintillation monitoring and modelling by the European groups involved in COST 296. Several of these groups have organized scintillation measurement campaigns at low and high latitudes. Some characteristic results obtained from the measured data are presented. The paper also addresses the modeling activities: four models, based on phase screen techniques, with different options and application domains are detailed. Finally some new trends for research topics are given. This includes the wavelet analysis, the high latitudes analysis, the construction of scintillation maps and the mitigation techniques

B Cell Depletion in HIV-1 Subtype A Infected Ugandan Adults: Relationship to CD4 T Cell Count, Viral Load and Humoral Immune Responses

To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001). HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb) titers against subtype A (p = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection

Clinical and Virological Study of Dengue Cases and the Members of Their Households: The Multinational DENFRAME Project

Dengue is the most important mosquito-borne viral disease in humans. This disease is now endemic in more than 100 countries and threatens more than 2.5 billion people living in tropical countries. It currently affects about 50 to 100 million people each year. It causes a wide range of symptoms, from an inapparent to mild dengue fever, to severe forms, including dengue hemorrhagic fever. Currently no specific vaccine or antiviral drugs are available. We carried out a prospective clinical study in South-East Asia and Latin America, of virologically confirmed dengue-infected patients attending the hospital, and members of their households. Among 215 febrile dengue subjects, 177 agreed to household investigation. Based on our data, we estimated the proportion of dengue-infected household members to be about 45%. At the time of the home visit, almost three quarters of (29/39) presented an inapparent dengue infection. The proportion of inapparent dengue infection was higher in South-East Asia than in Latin America. These findings confirm the complexity of dengue disease in humans and the need to strengthen multidisciplinary research efforts to improve our understanding of virus transmission and host responses to dengue virus in various human populations

Design of a high performance wideband corrugated horn

We present the results of investigations in order to design wideband horn antennas both with respect to the return loss and the cross polarisation level. The work reported was intended to design a microwave source with less than 40 dB VSWR, less than -50 dB cross polarisation and low sidelobes over 20% bandwidth. Two analysis techniques may be used for the simulation of such antennas: the method of moment (MoM) based on solution of integral equations, and the scattering matrix technique. The results presented have been obtained using the MoM technique by means of 1D integral equation

Pneumococcal surface protein A (PspA) is effective at eliciting T cell-mediated responses during invasive pneumococcal disease in adults

Humoral immune response is essential for protection against invasive pneumococcal disease and this property is the basis of the polysaccharide-based anti-pneumococcal vaccines. Pneumococcal surface protein A (PspA), a cell-wall-associated surface protein, is a promising component for the next generation of pneumococcal vaccines. This PspA antigen has been shown to stimulate an antibody-based immunity. In the present study, we evaluated the capacity of PspA to stimulate CD4(+) T cells which are needed for the correct development of a B cell based immune response in humans. Cellular immunity to PspA was evaluated by whole-blood culture with different pneumococcal antigens, followed by flow cytometric detection of activated CD4(+)CD25(+) T cells. T cell-mediated immune responses to recombinant PspA proteins were assessed in acute-phase and convalescent blood from adults with invasive pneumococcal disease and in blood from healthy subjects. All cases had detectable antibodies against PspA on admission. We found that invasive pneumococcal disease induced transient T cell depletion but adaptive immune responses strengthened markedly during convalescence. The increased production of both interleukin (IL)-10 and interferon (IFN)-γ during convalescence suggests that these cytokines may be involved in modulating antibody-based immunity to pneumococcal disease. We demonstrated that PspA is efficient at eliciting T cell immune responses and antibodies to PspA. This study broadens the applicability of recombinant PspA as potent pneumococcal antigen for vaccination against S. pneumoniae

Perception of PrEP-related stigma in PrEP users: Results from the ANRS-PREVENIR cohort

Introduction: Since the advent of HIV pre-exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception.Method: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS-PREVENIR study who answered the outcome question.Results: Almost one-third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97-0.99) and more psychologically vulnerable participants (i.e., lower self-esteem score [aOR 0.98; 95% CI 0.96-0.99] and higher depression score [aOR 1.02; 95% CI 1.00-1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51-0.88) and friends (aOR 0.79; 95% CI 0.66-0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69-0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67-0.96) were less likely to have this perception.Discussion: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable.Trial registration: ClinicalTrials.gov NCT03113123