Longitudinal microarray analysis of cell surface antigens on peripheral blood mononuclear cells from HIV+ individuals on highly active antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>The efficacy of highly active antiretroviral therapy (HAART) determined by simultaneous monitoring over 100 cell-surface antigens overtime has not been attempted. We used an antibody microarray to analyze changes in the expression of 135 different cell-surface antigens overtime on PBMC from HIV+ patients on HAART. Two groups were chosen, one (n = 6) achieved sustainable response by maintaining below detectable plasma viremia and the other (n = 6) responded intermittently. Blood samples were collected over an average of 3 years and 5–8 time points were selected for microarray assay and statistical analysis.</p> <p>Results</p> <p>Significant trends over time were observed for the expression of 7 cell surface antigens (CD2, CD3epsilon, CD5, CD95, CD36, CD27 and CD28) for combined patient groups. Between groups, expression levels of 10 cell surface antigens (CD11a, CD29, CD38, CD45RO, CD52, CD56, CD57, CD62E, CD64 and CD33) were found to be differential. Expression levels of CD9, CD11a, CD27, CD28 and CD52, CD44, CD49d, CD49e, CD11c strongly correlated with CD4+ and CD8+ T cell counts, respectively.</p> <p>Conclusion</p> <p>Our findings not only detected markers that may have potential prognostic/diagnostic values in evaluating HAART efficacy, but also showed how density of cell surface antigens could be efficiently exploited in an array-like manner in relation to HAART and HIV-infection. The antigens identified in this study should be further investigated by other methods such as flow cytometry for confirmation as biological analysis of these antigens may help further clarify their role during HAART and HIV infection.</p

Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection

<p>Abstract</p> <p>Background</p> <p>Elite non-progressors (plasma viral load <50 copies/ml while antiretroviral naive) constitute a tiny fraction of HIV-infected individuals. After 12 years follow-up of a cohort of 13 long-term non-progressors (LTNP) identified from 135 individuals with transfusion-acquired HIV infection, 5 remained LTNP after 23 to 26 years infection, but only 3 retained elite LTNP status. We examined the mechanisms that differentiated delayed progressors from LTNP in this cohort.</p> <p>Results</p> <p>A survival advantage was conferred on 12 of 13 subjects, who had at least one host genetic factor (HLA, chemokine receptor or TLR polymorphisms) or viral attenuating factor (defective <it>nef</it>) associated with slow progression. However, antiviral immune responses differentiated the course of disease into and beyond the second decade of infection. A stable p24-specific proliferative response was associated with control of viraemia and retention of non-progressor status, but this p24 response was absent or declined in viraemic subjects. Strong Gag-dominant cytotoxic T lymphocyte (CTL) responses were identified in most LTNP, or Pol dominant-CTL in those with <it>nef</it>-defective HIV infection. CTL were associated with control of viraemia when combined with p24 proliferative responses. However, CTL did not prevent late disease progression. Individuals with sustained viral suppression had CTL recognising numerous Gag epitopes, while strong but restricted responses to one or two immunodominant epitopes was effective for some time, but failed to contain viraemia over the course of this study. Viral escape mutants at a HLA B27-restricted Gag-p24 epitope were detected in only 1 of 3 individuals, whereas declining or negative p24 proliferative responses occurred in all 3 concurrent with an increase in viraemia.</p> <p>Conclusion</p> <p>Detectable viraemia at study entry was predictive of loss of LTNP status and/or disease progression in 6 of 8, and differentiated slow progressors from elite LTNP who retained potent virological control. Sustained immunological suppression of viraemia was independently associated with preserved p24 proliferative responses, regardless of the strength and breadth of the CTL response. A decline in this protective p24 response preceded or correlated with loss of non-progressor status and/or signs of disease progression.</p

Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo

In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection

Search for resonant diphoton production with the D0 detector

We present a search for a narrow resonance in the inclusive diphoton final state using 2.7 fb-1 of data collected with the D0 detector at the Fermilab Tevatron ppbar Collider. We observe good agreement between the data and the background prediction, and set the first 95% C.L. upper limits on the production cross section times the branching ratio for decay into a pair of photons for resonance masses between 100 and 150 GeV. This search is also interpreted in the context of several models of electroweak symmetry breaking with a Higgs boson decaying into two photons.Comment: 7 pages, 3 figures

Search for charged Higgs bosons decaying to top and bottom quarks in ppbar collisions

We describe a search for production of a charged Higgs boson, q \bar{q'} -> H^+, reconstructed in the t\bar{b} final state in the mass range 180 <= M_{H^+} <= 300 GeV. The search was undertaken at the Fermilab Tevatron collider with a center-of-mass energy sqrt{s} = 1.96 TeV and uses 0.9 fb^{-1} of data collected with the D0 detector. We find no evidence for charged Higgs boson production and set upper limits on the production cross section in the Types I, II and III two-Higgs-doublet models (2HDMs). An excluded region in the (M_{H^+},tan\beta) plane for Type I 2HDM is presented.Comment: Submitted to Phys. Rev. Letter

Search for right-handed W bosons in top quark decay

We present a measurement of the fraction f+ of right-handed W bosons produced in top quark decays, based on a candidate sample of $t\bar{t}$ events in the lepton+jets decay mode. These data correspond to an integrated luminosity of 230pb^-1, collected by the DO detector at the Fermilab Tevatron $p\bar{p}$ Collider at sqrt(s)=1.96 TeV. We use a constrained fit to reconstruct the kinematics of the $t\bar{t}$ and decay products, which allows for the measurement of the leptonic decay angle $\theta^*$ for each event. By comparing the $\cos\theta^*$ distribution from the data with those for the expected background and signal for various values of f+, we find f+=0.00+-0.13(stat)+-0.07(syst). This measurement is consistent with the standard model prediction of f+=3.6x10^-4.Comment: Submitted to Physical Review D Rapid Communications 7 pages, 3 figure

Search for scalar leptoquarks and T-odd quarks in the acoplanar jet topology using 2.5 fb-1 of ppbar collision data at sqrt(s)=1.96 TeV

A search for new physics in the acoplanar jet topology has been performed in 2.5 fb-1 of data from ppbar collisions at sqrt(s)=1.96 TeV, recorded by the D0 detector at the Fermilab Tevatron Collider. The numbers of events with exactly two acoplanar jets and missing transverse energy are in good agreement with the standard model expectations. The result of this search has been used to set a lower mass limit of 205 GeV at the 95% C.L. on the mass of a scalar leptoquark when this particle decays exclusively into a quark and a neutrino. In the framework of the Little Higgs model with T-parity, limits have also been obtained on the T-odd quark mass as a function of the T-odd photon mass

Observation of ZZ production in ppbar collisions at sqrt(s) = 1.96 TeV

We present an observation for ZZ -> l+l-l'+l'- (l, l' = e or mu) production in ppbar collisions at a center-of-mass energy of sqrt(s) = 1.96 TeV. Using 1.7 fb-1 of data collected by the D0 experiment at the Fermilab Tevatron Collider, we observe three candidate events with an expected background of 0.14 +0.03 -0.02 events. The significance of this observation is 5.3 standard deviations. The combination of D0 results in this channel, as well as in ZZ -> l+l-nunubar, yields a significance of 5.7 standard deviations and a combined cross section of sigma(ZZ) = 1.60 +/- 0.63 (stat.) +0.16 -0.17 (syst.) pb.Comment: 7 pages, 1 figure, 2 tables Modified slightly following review proces