Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines

Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater than 50% of the viruses included in a high throughput PhenoSense neutralization assay when these immuongens were tested as a DNA prime followed by a fixed 5-valent gp120 protein vaccine boost. The new polyvalent formulation, using five gp120 immunogens selected from this subgroup, elicited improved quality of antibody responses in rabbits than the previous DP6-001 formulation. More significantly, this new polyvalent formulation elicited higher antibody responses against a panel of gp70V1/V2 antigens expressing V1/V2 sequences from diverse subtypes. Bioinformatics analysis supports the design of a 4-valent or 5-valent formulation using gp120 immunogens from this screening study to achieve a broad coverage against 16 HIV-1 subtypes

Therapeutic DNA vaccination of vertically HIV-infected children: Report of the first pediatric randomised trial (PEDVAC)

Subjects: Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm³. Intervention: Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results: Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions: The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration: clinicaltrialsregister.eu 2007-002359-18; 2007-002359-18/I

"Traduzione e creatività”, in Bruti Silvia, Teoria della Traduzione Audiovisiva

Unità didattica (con esercizi) all’interno del primo modulo per Master – online – universitario europeo di II livello in traduzione audiovisiva, promosso dal Dipartimento di Lingue e Letterature Straniere dell’Università di Parma in collaborazione con l’Università Autonoma di Barcellona (UAB

Transpersonale e transgenerazionale

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La percezione soggettiva del tempo. Ricerca applicata alla pedagogia del lavoro

Il tempo scandito dalle lancette dell’orologio, il cosiddetto “tempo oggettivo” è profondamente differente da quello percepito dall’individuo. Partendo da questa prima ipotesi, direttamente connessa con la modalità soggettiva di “vivere” il tempo, definita orizzonte temporale, si cercherà di capire quanto essa influisca sui diversi ambiti della vita delle persone, sui loro atteggiamenti e sui loro vissuti. In seconda battuta, la ricerca indaga se ogni nostra decisione può essere influenzata, al di là della nostra consapevolezza, da una o più prospettive temporali, ossia dal processo che ci permette di organizzare le nostre esperienze e i nostri vissuti in categorie temporali. Non ultimo ci occuperemo di capire se alcuni determinati orizzonti temporali in contesti specifici siano maggiormente funzionali e adattavi rispetto ad altri

Healthy Lifestyle, Well-being, Physical Activity, Sport, and Scholastic/academic Performance: Interactions and Connections.

The physical activity and sport are key elements for a healthy lifestyle. However, a little-investigated element is the presence of a possible relationship between school or academic performance and the participation in physical activity and sport in groups of preadolescents and adolescents. In order to clarify the complex relationship between mind and body in preadolescence and adolescence, the present discussion investigates the causal and direct relationship between sport activity and performance; and describes how this relationship can be mediated by the sense of self-esteem and self-efficacy; and investigates the relationship between group sports practice and school or academic performance

Healthy Lifestyle, Well-being, Physical Activity, Sport, and Scholastic/academic Performance: Interactions and Connections

The physical activity and sport are key elements for a healthy lifestyle. However, a little-investigated element is the presence of a possible relationship between school or academic performance and the participation in physical activity and sport in groups of preadolescents and adolescents. In order to clarify the complex relationship between mind and body in preadolescence and adolescence, the present discussion investigates the causal and direct relationship between sport activity and performance; and describes how this relationship can be mediated by the sense of self-esteem and self-efficacy; and investigates the relationship between group sports practice and school or academic performance

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4⁺ T-Cells

At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and decreased both ADCC specific for helical V2 and efferocytosis. Remarkably, IGF-1 also reduced the expression of CCR5 on vaccine-induced CD4+ gut-homing T-cells, compensating for its negative effect on ADCC and efferocytosis and resulting in equivalent vaccine efficacy (71% with IGF-1 and 69% without)

Correction: ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type.

[This corrects the article DOI: 10.1371/journal.ppat.1008121.]

First experimental validation of silicon-based sensors for monitoring ultra-high dose rate electron beams

Monitoring Ultra-High Dose Rate (UHDR) beams is one of the multiple challenges posed by the emergent FLASH radiotherapy. Technologies (i.e., gas-filled ionization chambers) nowadays used in conventional radiotherapy are no longer effective when applied to UHDR regimes, due to the recombination effect they are affected by, and the time required to collect charges. Exploiting the expertise in the field of silicon sensors’ applications into clinics, the medical physics group of the University and INFN Torino is investigating thin silicon sensors as possible candidates for UHDR beam monitoring, exploiting their excellent spatial resolution and well-developed technology. Silicon sensors of 30 and 45 µm active thicknesses and 0.25, 1 and 2 mm2 active areas were tested at the SIT ElectronFlash machine (CPFR, Pisa) on 9 MeV electron beams, featuring a pulse duration of 4 µs, a frequency of 1 Hz, and a dose-per-pulse ranging from 1.62 to 10.22 Gy/pulse. The silicon sensors were positioned at the exit of the ElectronFlash applicator, after a solid water build-up slab, and were readout both with an oscilloscope and with a multi-channel front-end readout chip (TERA08). A response linearity extending beyond 10 Gy/pulse was demonstrated by comparison with a reference dosimeter (FlashDiamond), thus fulfilling the first requirement of a potential application in UHDR beam monitoring