Development and laboratory production of virus-like immune-stimulating complexes based on saponins and evaluation of their adjuvant potential using mice immunisation with influenza antigens

The COVID-19 pandemic has exacerbated the public’s need for effective vaccines. Consequently, significant financial support has been provided to developers of a number of innovative vaccines, including the vaccines with saponin-based adjuvants. In 2021, the World Health Organisation recommended Mosquirix, the first malaria vaccine, which contains a saponin adjuvant. An anti-covid vaccine by Novavax is in the approval phase. A promising approach to vaccine development is presented by the use of virus-like immune-stimulating complexes (ISCOMs) containing saponins and by the creation of combinations of ISCOMs with antigens. The aim of the study was to develop, produce and characterise virus-like immune-stimulating complexes based on saponins of Quillaja saponaria, as well as similar saponins of Russian-sourced Polemonium caeruleum. Materials and methods: The ISCOM adjuvants, Matrix-BQ and Matrix-BP, were produced using liquid chromatography and examined using electron microscopy. Balb/c mice were immunised intraperitoneally and intramuscularly with ISCOM-antigen preparations. Afterwards, the immunised animals were challenged with the influenza virus strain, A/California/4/2009(H1N1)pdm09, adapted and lethal to mice. The serum samples were examined using haemagglutination inhibition (HI) tests. Results: The authors produced the ISCOMs containing saponins of Quillaja saponaria and Polemonium caeruleum. After one intramuscular injection of either of the ISCOM-antigen preparations with 1 µg of each of A/Brisbane/02/2018 (H1N1) pdm09, A/Kansas/14/2017 (H3N2), and B/Phuket/3073/2013 haemagglutinin antigens (HAs), HI tests detected serum antibody titres to the corresponding antigens of ≥1:40. Two intramuscular injections of the ISCOM-antigen preparation containing 50 ng of each of the HAs and Matrix-BQ resulted in a protective response. In some animals, two intraperitoneal injections of ISCOM-antigen preparations resulted in the maximum antibody titre to the A/Kansas/14/2017 (H3N2) vaccine strain of 1:20,480. Two intramuscular injections of a test preparation containing 5 µg, 1 µg, 200 ng, or 50 ng of each of the HAs and Matrix-BQ or a control preparation containing 5 µg, 1 µg, or 200 ng of each of the HAs (commercially available vaccines) to the mice that were afterwards infected with the lethal influenza strain protected the experimental animals from death. Conclusions: The ISCOM-based preparations had high immunostimulatory activity in the mouse-model study. The presented results indicate the potential of further studies of ISCOM-based preparations in terms of both vaccine and immunotherapeutic development

Measurement of the isotopic composition of hydrogen and helium nuclei in cosmic rays with the PAMELA experiment

The satellite-borne experiment PAMELA has been used to make new measurements of cosmic ray H and He isotopes. The isotopic composition was measured between 100 and 600 MeV/n for hydrogen and between 100 and 900 MeV/n for helium isotopes over the 23rd solar minimum from July 2006 to December 2007. The energy spectrum of these components carries fundamental information regarding the propagation of cosmic rays in the galaxy which are competitive with those obtained from other secondary to primary measurements such as B/C.Comment: 11 pages, 11 figures, 5 tables. To appear in Astrophysical Journa

ПРЕДПОСЫЛКИ И ОЖИДАНИЯ ВНЕДРЕНИЯ СИСТЕМЫ МЕНЕДЖМЕНТА КАЧЕСТВА В МУНИЦИПАЛЬНОМ БЮДЖЕТНОМ УЧРЕЖДЕНИИ ЗДРАВООХРАНЕНИЯ

Quality management system (QMS) is an effective instrument of medical care quality management. The article describes prerequisites and expectations of the system implementation in municipal budgetary health-care institution. The necessity of work under QMS is substantiated. The research goal is the analysis of prerequisites and expectations of quality management system introduction basing on international standards for controllability improvement of municipal health-care institution.Система менеджмента качества (СМК) – эффективный инструмент управления качеством медицинской помощи. В статье отражены предпосылки и ожидания внедрения системы в муниципальном бюджетном учреждении здравоохранения. Обоснована необходимость работы в рамках СМК. Цель исследования – анализ предпосылок и ожиданий внедрения системы менеджмента качества на основе международных стандартов для совершенствования управляемости муниципального учреждения здравоохранения

Measurement of boron and carbon fluxes in cosmic rays with the PAMELA experiment

The propagation of cosmic rays inside our galaxy plays a fundamental role in shaping their injection spectra into those observed at Earth. One of the best tools to investigate this issue is the ratio of fluxes for secondary and primary species. The boron-to-carbon (B/C) ratio, in particular, is a sensitive probe to investigate propagation mechanisms. This paper presents new measurements of the absolute fluxes of boron and carbon nuclei, as well as the B/C ratio, from the PAMELA space experiment. The results span the range 0.44 - 129 GeV/n in kinetic energy for data taken in the period July 2006 - March 2008

Trapped proton fluxes at low Earth orbits measured by the PAMELA experiment

We report an accurate measurement of the geomagnetically trapped proton fluxes for kinetic energy above > 70 MeV performed by the PAMELA mission at low Earth orbits (350-610 km). Data were analyzed in the frame of the adiabatic theory of charged particle motion in the geomagnetic field. Flux properties were investigated in detail, providing a full characterization of the particle radiation in the South Atlantic Anomaly region, including locations, energy spectra and pitch angle distributions. PAMELA results significantly improve the description of the Earth's radiation environment at low altitudes placing important constraints on the trapping and interaction processes, and can be used to validate current trapped particle radiation models.Comment: 22 pages, 5 figure

The Lake Baikal neutrino experiment: selected results

We review the present status of the lake Baikal Neutrino Experiment and present selected physical results gained with the consequetive stages of the stepwise increasing detector: from NT-36 to NT-96. Results cover atmospheric muons, neutrino events, very high energy neutrinos, search for neutrino events from WIMP annihilation, search for magnetic monopoles and environmental studies. We also describe an air Cherenkov array developed for the study of angular resolution of NT-200.Comment: 25 pages, 12 figures. To appear in the Procrrdings of International Conference on Non-Accelerator New Physics, June 28 - July 3, 1999, Dubna, Russi

BAIKAL experiment: status report

We review the present status of the Baikal Neutrino Project and present the results obtained with the deep underwater neutrino telescope NT-200.Comment: 4 pages, 3 figures. Presented at TAUP 2001 (7th international workshop on Topics in Astroparticle and Underground Physics), Sep. 2001, Laboratori Nazionali del Gran Sasso, Assergi, Ital