Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus

Abstract Objectives Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. Methods This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3(+)CD8(+)CD38(+)) and B-(CD19(+)CD80/86(+) and CD19(+)CD10-CD21(low)CD27(+)) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt] DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR. Results At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T-and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001). Conclusions Long-term mART is associated with higher levels of T-and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection

Neutrino Electromagnetic Form Factor and Oscillation Effects on Neutrino Interaction With Dense Matter

The mean free path of neutrino - free electron gas interaction has been calculated by taking into account the neutrino electromagnetic form factors and the possibility of neutrino oscillation. It is shown that the form factor effect becomes significant for a neutrino magnetic moment \mu_\nu > 10^{-10} mu_B and for a neutrino radius R > 10^{-6} MeV^{-1}. The mean free path is found to be sensitive to the nu_e-nu_mu and nu_e-nu_e^R transition probabilities.Comment: 4 pages, 3 eps figures, accepted for publication in Phys. Rev.

Neutron Fraction and Neutrino Mean Free Path Predictions in Relativistic Mean Field Models

The equation of state (EOS) of dense matter and neutrino mean free path (NMFP) in a neutron star have been studied by using relativistic mean field models motivated by effective field theory (ERMF). It is found that the models predict too large proton fractions, although one of the models (G2) predicts an acceptable EOS. This is caused by the isovector terms. Except G2, the other two models predict anomalous NMFP. In order to minimize the anomaly, besides an acceptable EOS, a large M* is favorable. A model with large M* retains the regularity in the NMFP even for a small neutron fraction.Comment: 4 pages, 5 figures, accepted for publication in Phys. Rev.

MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial.

BACKGROUND: Immunotherapy offers a promising novel approach for the treatment of cancer and both adoptive T-cell transfer and immune modulation lead to regression of advanced melanoma. However, the potential synergy between these two strategies remains unclear. METHODS: We investigated in 12 patients with advanced stage IV melanoma the effect of multiple MART-1 analog peptide vaccinations with (n = 6) or without (n = 6) IMP321 (LAG-3Ig fusion protein) as an adjuvant in combination with lymphodepleting chemotherapy and adoptive transfer of autologous PBMCs at day (D) 0 (Trial registration No: NCT00324623). All patients were selected on the basis of ex vivo detectable MART-1-specific CD8 T-cell responses and immunized at D0, 8, 15, 22, 28, 52, and 74 post-reinfusion. RESULTS: After immunization, a significant expansion of MART-1-specific CD8 T cells was measured in 83% (n = 5/6) and 17% (n = 1/6) of patients from the IMP321 and control groups, respectively (P &lt; 0.02). Compared to the control group, the mean fold increase of MART-1-specific CD8 T cells in the IMP321 group was respectively &gt;2-, &gt;4- and &gt;6-fold higher at D15, D30 and D60 (P &lt; 0.02). Long-lasting MART-1-specific CD8 T-cell responses were significantly associated with IMP321 (P &lt; 0.02). At the peak of the response, MART-1-specific CD8 T cells contained higher proportions of effector (CCR7⁻ CD45RA⁺/⁻) cells in the IMP321 group (P &lt; 0.02) and showed no sign of exhaustion (i.e. were mostly PD1⁻CD160⁻TIM3⁻LAG3⁻2B4⁺/⁻). Moreover, IMP321 was associated with a significantly reduced expansion of regulatory T cells (P &lt; 0.04); consistently, we observed a negative correlation between the relative expansion of MART-1-specific CD8 T cells and of regulatory T cells. Finally, although there were no confirmed responses as per RECIST criteria, a transient, 30-day partial response was observed in a patient from the IMP321 group. CONCLUSIONS: Vaccination with IMP321 as an adjuvant in combination with lymphodepleting chemotherapy and adoptive transfer of autologous PBMCs induced more robust and durable cellular antitumor immune responses, supporting further development of IMP321 as an adjuvant for future immunotherapeutic strategies

Gerasimov-Drell-Hearn Sum Rule and the Discrepancy between the New CLAS and SAPHIR Data

Contribution of the K^+\Lambda channel to the Gerasimov-Drell-Hearn (GDH) sum rule has been calculated by using the models that fit the recent SAPHIR or CLAS differential cross section data. It is shown that the two data sets yield quite different contributions. Contribution of this channel to the forward spin polarizability of the proton has been also calculated. It is also shown that the inclusion of the recent CLAS C_x and C_z data in the fitting data base does not significantly change the result of the present calculation. Results of the fit, however, reveal the role of the S_{11}(1650), P_{11}(1710), P_{13}(1720), and P_{13}(1900) resonances for the description of the C_x and C_z data. A brief discussion on the importance of these resonances is given. Measurements of the polarized total cross section \sigma_{TT'} by the CLAS, LEPS, and MAMI collaborations are expected to verify this finding.Comment: 15 pages, 8 figure