Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

Development of vaccines based on adenoviral vectors: A review of foreign clinical studies (Part 1)

There are no effective approaches to treatment and prevention of many infectious diseases representing a significant danger to humans. So far, mass vaccine immunization is among the most efficient and widely used approaches to prevent outbreaks of viral and bacterial infections. Mass immunization helps to reduce the number of carriers of infections, thus significantly decreasing probability of infection dissemination. Recent promising developments include genetically engineered vaccines based on adenoviral vectors, many of which are already at various stages of clinical trials. Genetic immunization with recombinant adenovirus-based vaccines allows delivery of the genes encoding only required antigens to human cells, thus allowing avoidance of conventional vaccines, e.g., live pathogenic viruses and bacteria, and providing versatile technologies for vaccine development. These advances significantly reduce the time needed for vaccine production and, respectively, the development and creation of new vaccines, thus being an important factor in decreasing risk of epidemics and pandemics. Advantages of adenoviral vectors include high ability of penetration into human cells, a potential for induction of both humoral and cellular immune response, rather long and active production of antigens following administration of adenoviral vectors into the human, safe usage, ease of obtaining preparative quantities of vaccines. In this review, we provide information about the ongoing worldwide clinical trials of adenoviral vector-based vaccines against various infectious diseases, like as to consider selection parameters of volunteers participating in the testing, vaccination schedule, doses and methods of drug administration, results of completed experiments, and preliminary data on currently ongoing research. © 2017, SPb RAACI

Features of the course of contemporary intestinal amebiasis

Acute intestinal infections, including intestinal amebiasis, remain a pressing public health problem. Amebiasis still represents an important and partially solved problem to health care. In the Astrakhan region, intestinal amebiasis is being continuously recorded. We analyzed the clinical picture of acute intestinal amebiasis in 150 adult patients dominated by female patients comprising 60.7%, aged 18 to 79 years old, and treated within 2010–2016 at the Regional Infectious Clinical Hospital. All patients were mostly of young and middle age (up to 50 years) — 108 patients. More than 50% of patients were admitted to the hospital within the first three days of the disease. However, in 35 cases (23.3%), late hospitalization was carried out (5 days after the onset). Proper diagnosis was made to 44 patients (29.3%), most commonly diagnosing preliminarily with acute gastroenteritis and acute dysentery. All cases of intestinal amebiasis were confirmed by detecting in the feces of patients with a vegetative form of entamoeba histolytica. The disease was featured with sporadic course, being mostly recorded during the summer-autumn period (78.0%). In 142 patients (94.7%), the moderate severity was observed. Cardiovascular disorders were mainly found in severe amebiasis as well as patients comorbid with cardiovascular diseases. A coprological method was used to confirm the diagnosis. Microscopic examination of feces was carried out immediately after defecation (warm type). A combination therapy was applied to patients with intestinal amebiasis. A great attention was paid to patient nutrition: high-protein sparing diet, grated food. Patients with ulcerative colitis received individualized diet (restricted carbohydrates, exclusion of milk and fiber). Etiotropic therapy was carried out with using 5-nitroimidazole preparations: metronidazole (Trichopol, Flagin, Tiberal), MacGioror, Tinidazole (Phasycin) combined with tetracycline. The treatment included group B vitamin cocktail, methyluracil (suppository), enzymes (creon, mezim, pancreatin), enterosorbents (smecta, polyphepan, enterosgel), antispasmodics (no-spa, drotaverin). Patients were administered with therapeutic microenemas containing furacilin solution, rosehip oil, and sea buckthorn oil. Infusion therapy consisting of polyionic solutions was applied by assessing blood electrolyte level. Fresh frozen plasma and albumin were transfused upon decline of serum protein and albumin level. Packed erythrocytes Erythrocyte mass and hemostatic drugs were injected in case of severe intestinal amebiasis if indicated: dicynone, cryoprecipitate, and calcium preparations. Finally, anemia cases were treated as well. In all cases, the disease outcome was favorable, without any mortality. Complications were noted in the form of intestinal bleeding observed in 6 patients (4.0%), wherein amebiasis proceeded together with ulcerative colitis. Acute intestinal amebiasis is currently featured with typical clinical picture that proceeds with less severe symptoms. Intestinal bleeding was observed in patients with intestinal amoebiasis in combination with ulcerative colitis. Chronization of intestinal amebiasis occurs in single cases (3.9%).</jats:p

Сlinical and epidemiological characteristics of botulism

Clinical and epidemiological characteristics of botulism in the Astrakhan region for the period from 2013 to 2019 are presented. 37 people with a diagnosis of Botulism were under observation. It was found that most often (28 (75.7%) cases) patients associated their disease with the use of canned home-made products. Canned vegetables (cucumbers, tomatoes, vegetable salad, eggplant, cabbage) were consumed by 18 (48.7%) people, mushrooms 10 (27%), dried fish 7 (18.9%), herring-balyk 1 (2.7%) and home-made liver pate-1 (2.7%) patient. The incubation period in the observed patients was on average 2.4 days. It lasted 12 days in 24 (64.9%) patients, 3-5 days in 12 (32.4%) patients, and 6 days in 1 (2.7%) patient. According to the severity of the condition, 17 (45.9%) patients were hospitalized in the intensive care unit. Severe course of the disease was in 17 (45.9%) patients, moderate-in 20 (54.1%) patients. Early and persistent symptoms in all patients were marked muscle weakness, in 78.4% of patients dizziness, in 83.8% of patients difficulty walking and unsteadiness of gait. In 34 (91.9%) patients, the most pronounced symptoms were ophthalmoplegic: blurred vision, fog, flies in front of the eyes, inability to read the text. In General, up to 10 cases of botulism are registered annually in the Astrakhan region. Almost half of the patients (45.9%) have severe botulism. The disease is mostly sporadic and is associated with the use of canned vegetables and home-made mushrooms. In addition, cases of botulism associated with the use of dried fish have become more frequent in the Astrakhan region. Late hospitalization was observed in 1/3 of patients (11 (29.7%) cases) with botulism. This is due to untimely diagnosis at the pre-hospital stage and late access of patients to medical care.</jats:p

DEVELOPMENT OF VACCINES BASED ON ADENOVIRAL VECTORS: A REVIEW OF FOREIGN CLINICAL STUDIES (PART 1)

There are no effective approaches to treatment and prevention of many infectious diseases representing a significant danger to humans. So far, mass vaccine immunization is among the most efficient and widely used approaches to prevent outbreaks of viral and bacterial infections. Mass immunization helps to reduce the number of carriers of infections, thus significantly decreasing probability of infection dissemination. Recent promising developments include genetically engineered vaccines based on adenoviral vectors, many of which are already at various stages of clinical trials. Genetic immunization with recombinant adenovirus-based vaccines allows delivery of the genes encoding only required antigens to human cells, thus allowing avoidance of conventional vaccines, e.g., live pathogenic viruses and bacteria, and providing versatile technologies for vaccine development. These advances significantly reduce the time needed for vaccine production and, respectively, the development and creation of new vaccines, thus being an important factor in decreasing risk of epidemics and pandemics. Advantages of adenoviral vectors include high ability of penetration into human cells, a potential for induction of both humoral and cellular immune response, rather long and active production of antigens following administration of adenoviral vectors into the human, safe usage, ease of obtaining preparative quantities of vaccines. In this review, we provide information about the ongoing worldwide clinical trials of adenoviral vector-based vaccines against various infectious diseases, like as to consider selection parameters of volunteers participating in the testing, vaccination schedule, doses and methods of drug administration, results of completed experiments, and preliminary data on currently ongoing research