A bélmikrobiom szerepe az alkoholos és nem alkoholos zsírmáj kialakulásában, progressziójában

A nem alkoholos zsírmáj járványszerű terjedése nem független az elhízás és metabolikus betegségek elmúlt évtizedekben tapasztalt szomorú térhódításától a fejlett világban. A mikrobiomkutatás új távlatokat nyitott a patomechanizmus megértésében és a progresszióval fenyegető formák felismerésében. Ebben kulcsszerepet játszik a bélflóra összetételének és funkciójának változásával járó gyulladás és az intesztinális barrier sérülése, amelyek célzott helyreállítása hozzájárulhat a betegség sikeres kezeléséhez és a progresszió megelőzéséhez. Érdekes módon, hasonló mechanizmusok vezérlik az alkoholos májkárosodás patogenezisét és a két betegségspektrum a korábbi elképzelésekkel ellentétben egy kontinuumot alkot. A betegség tünetei helyett a gondozási gyakorlat célja tehát az oki tényezők korrekciója: mindennek egyik fő eleme a célzott táplálásterápia, amelyben a fizikai aktivitás és egyéb életmódtényezőkön túl specifikus probiotikumok használata is szerepet kaphat. További klinikai vizsgálatok szükségesek a rutin klinikai gyakorlat számára pontos irányelvek meghatározásához

Single DermaVir Immunization: Dose-Dependent Expansion of Precursor/Memory T Cells against All HIV Antigens in HIV-1 Infected Individuals

BACKGROUND: The GIHU004 study was designed to evaluate the safety and immunogenicity of three doses of DermaVir immunization in HIV-infected subjects on fully suppressive combination antiretroviral therapy (cART). METHODOLOGY/PRINCIPAL FINDINGS: This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted to epidermal Langerhans cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes. Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining lymph node via ∼8 million Langerhans cells located in 80 cm(2) epidermis area. The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir-associated side effects were mild, transient and not dose-dependent. Boosting of HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was detected against several antigens in every subject of the medium dose cohort. The striking result was the dose-dependent expansion of HIV-specific precursor/memory T cells with high proliferation capacity. In low, medium and high dose cohorts this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year, respectively, compared to baseline. CONCLUSIONS/SIGNIFICANCE: Single immunization with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV-infected individuals. Based on the potent induction of Gag, Tat and Rev-specific memory T cells, especially in the medium dose cohort, we speculate that DermaVir boost T cell responses specific to all the 15 HIV antigens expressed from the single DNA. For durable immune reactivity repeated DermaVir immunization might be required since the frequency of DermaVir-boosted HIV-specific memory T cells decreased during the 48-week follow up. TRIAL REGISTRATION: ClinicalTrial.gov NCT00712530

Precision COVID-19 Vaccine with Companion Diagnostics

Although disease enhancement by antibodies has been described for corona and other viruses, nobody can predict whether such antibodies induced by the vaccine will not be harmful, especially after reinfection with a different strain. Alternative vaccines could induce memory T-cell responses, in the absence of antibodies, to kill newly infected cells. Preclinical testing of such precision vaccines is performed in silico without animal experiments since epitopes predicted to bind to three HLA class I molecules of a subject activate cytotoxic T-cell response with more than 80% probability. Data science can be utilized to select the immunogenic vaccine peptides from the coronavirus replicase protein and estimate the immune response rate in an HLA-genotyped population. Employing accessible platform technologies, a set of precision vaccines could be co-developed with an HLA-genotype based companion diagnostic to identify the vaccine that most likely nduces responses in the subject. The goal of precision vaccination is to convert the deadly COVID-19 into asymptomatic disease and to avoid the potential risk of disease enhancement

A Plasmid DNA immunogen expressing fifteen protein antigens and complex virus-like particles (VLP⁺) mimicking naturally occurring HIV

We describe here a single plasmid DNA immunogen representing the broadest antigen repertoire among HIV vaccine candidates. This pDNA was “ANTIGENeered” for the regulated expression of thirteen complete and two non-functional HIV protein antigens. These proteins self assemble into complex virus-like particles (VLP+). Multiple irreversible safety features were introduced by genetic modifications including the complete impairment of integration, reverse transcription, the function of Nef and the 3′LTR. Epitope analysis predicted that the pDNA-derived protein repertoire can potentially present over 3000 T cell epitopes. However, the expressed antigens have different potential to induce HIV-specific CD4+ and CD8+ T cells supporting our hypothesis that HIV vaccines should contain all possible regulatory and structural proteins. This immunogen is the active pharmaceutical ingredient of DermaVir, a therapeutic vaccine product candidate that recently successfully completed Phase II clinical trials and meets the safety, immunogenicity and cost requirements of an HIV vaccine

DermAll nanomedicine for allergen-specific immunotherapy

A novel allergen-specific immunotherapy for IgE-mediated allergies is presented in this paper, using an experimental allergic rhinitis model and a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin as model allergen. Over 50% reduction of symptoms was found as the immune system's balance was favorably altered toward more TH2-polarized immune responses