ABSTRACT
Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).
Subject(s)
Ebola Vaccines/immunology , Healthy Volunteers , Hemorrhagic Fever, Ebola/prevention & control , Adenoviridae/genetics , Adolescent , Adult , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Drug Carriers/administration & dosage , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Ebola Vaccines/administration & dosage , Female , Humans , Immunoglobulin G/blood , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Pain/chemically induced , Pain/epidemiology , Russia , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/immunology , Vesiculovirus/genetics , Volunteers , Young AdultABSTRACT
This article is dedicated to the current state and prospectives of cell engineering in nephrology from the point of view of military medicine. The review is based on publications from January 1, 2014, to June 1, 2015, and consists of two parts. In the first part the main directions of the cell engineering development are mentioned. The only two clinical trials existed in the field are discussed in more detail. The second part deals with prospectives of cell engineering in nephrology. It is shown that currently this field is in the stage of preclinical experimentation. Of the two known clinical trials the first has failed to demonstrate any effectiveness of cell engineering, the second--will be completed only at the end of 2016. Also, the review notes an extraordinary cost of cell engineering experiments in nephrology. The analysis of publications allows to come to a conclusion that the future progress in prevention and treatment of acute kidney injury could go not in the direction of cell engineering but rather non-cell technologies. One of. the practical consequence of such a conclusion is a necessity to continue the improvement of already existing methods of machine renal replacement therapy.
