Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment:interim analysis from a phase II clinical trial

BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV(+) individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient’s HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients’ cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4(+) and CD8(+) T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4(+) and CD8(+) T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4(+) T-cells. The number of candidates that increased in vitro the cytokine levels in CD4(+) and CD8(+) T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829, posted November 11th, 2016) SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12981-021-00426-z

Guidelines for the Management of Mucopolysaccharidosis Type I

Universidade Federal de São Paulo, Ctr Referencia Erros Inatos Metab, São Paulo, BrazilUniversidade Federal de São Paulo, Discipline Otorrinolaringol Pediat, São Paulo, BrazilPontificia Univ Catolica Campinas, São Paulo, BrazilUniv Ciencias Saude Alagoas, Maceio, BrazilUniv Fed Minas Gerais, Fac Med, Dept Propedeut Complementar, Belo Horizonte, MG, BrazilUniv São Paulo, Fac Med, Dept Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, Discipline Med & Biol Sono, São Paulo, BrazilUniv Estacio Sa, Florianopolis, SC, BrazilAPAE, Triagem Neonatal, Salvador, BA, BrazilUniv Fed Rio Grande do Sul, Dept Bioquim ICBS, Porto Alegre, RS, BrazilHosp Clin Porto Alegre, Serv Genet Med, Porto Alegre, RS, BrazilHosp Reabilitacao, Med Lab Rede Sarah, Belo Horizonte, MG, BrazilFundacao Hosp Estado Minas Gerais, Ctr Geral Pediat, Belo Horizonte, MG, BrazilHosp Restauracao Pernambuco, Serv Hepatol Infantil, Recife, PE, BrazilUniv Fed Minas Gerais, Fac Med, Dept Oftalmol, Belo Horizonte, MG, BrazilHosp Clin Porto Alegre, Setor Mucopolissacaridose, Serv Genet Med, Porto Alegre, RS, BrazilHosp Evangel Londrina Parana, Serv Hematol, Londrina, BrazilClin Doencas Metab Dr Ricardo Pires, Porto Alegre, RS, BrazilHosp Socor, Serv Ortopedia Pediat, Belo Horizonte, MG, BrazilUniv Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Ctr Pesquisas, Lab Terapia Genica, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Disciplina Disturbios Comunicacao Humana, Dept Fonoaudiol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Referencia Erros Inatos Metab, São Paulo, BrazilUniversidade Federal de São Paulo, Discipline Otorrinolaringol Pediat, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, Discipline Med & Biol Sono, São Paulo, BrazilUniversidade Federal de São Paulo, Disciplina Disturbios Comunicacao Humana, Dept Fonoaudiol, São Paulo, BrazilWeb of Scienc

JUNO sensitivity to the annihilation of MeV dark matter in the galactic halo

International audienceWe discuss JUNO sensitivity to the annihilation of MeV dark matter in the galactic halo via detecting inverse beta decay reactions of electron anti-neutrinos resulting from the annihilation. We study possible backgrounds to the signature, including the reactor neutrinos, diffuse supernova neutrino background, charged- and neutral-current interactions of atmospheric neutrinos, backgrounds from muon-induced fast neutrons and cosmogenic isotopes. A fiducial volume cut, as well as the pulse shape discrimination and the muon veto are applied to suppress the above backgrounds. It is shown that JUNO sensitivity to the thermally averaged dark matter annihilation rate in 10 years of exposure would be significantly better than the present-day best limit set by Super-Kamiokande and would be comparable to that expected by Hyper-Kamiokande

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially