Publikationsdatenbank

Recombinant canine distemper virus as a possible vector for the delivery of simian immunodeficiency virus antigens (2018)

Art

Hochschulschrift

Autor

Köhnke, Rebecca (WE 12)

Quelle

Berlin, 2018 — XIII, 198 Seiten

Sprache

Englisch

Verweise

URL (Volltext): https://refubium.fu-berlin.de/handle/fub188/23061

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Recombinant Canine Distemper Virus as a possible vector for the delivery of SIV antigens – establishment and evaluation of biosafety and immunogenicity of rCDV and rCDVgag in the ferret model HIV/AIDS has been termed one of the most devastating diseases of mankind. Due to the unique pathogenesis of this infection, medical therapy currently is unable to cure it. Preventative measures including improved education, supply and use of condoms and microbicides, and the use of antiretroviral drugs during pregnancy and breastfeeding of infected women have slowed the infection rates globally, but ultimately only a vaccine is believed to be able to control the pandemic. Simian Immunodeficiency Virus (SIV), a close relative of HIV that leads to comparable disease processes in Rhesus monkeys, has been employed to study pathogenesis, treatment and prevention of HIV infection, since it is non-pathogenic to humans. Development of potential vaccine candidates is posing a significant challenge to the research community. Various pathways have been explored; with viral vectors having shown considerable success over the last few years. Mucosal delivery of vector based vaccines is stipulated to elicit improved immune responses at mucosal virus entry sites. Ideal viral vectors share their main replication characteristics such as cell tropism and location of replication with the pathogenic virus in question, which enables them to deliver the included foreign antigens to the site of natural infection and replication. Members of the genus morbillivirus enter the host through mucosal membranes, infect preferably T cells in the gastrointestinal lymphoid tissue and cause significant immunosuppression in a susceptible host. This research study employs a live attenuated vaccine strain of Canine Distemper Virus (CDV), a morbillivirus non-pathogenic to humans but able to replicate in primate cells, that was rescued using reverse genetics and subsequently genetically engineered to contain the genetic information encoding the SIV gag protein, which is the most immunogenic of HIV/SIV proteins. The two recombinant viruses were evaluated in vitro to ensure infectivity and ability to replicate. The presence of the 55 kDa protein gag was confirmed. The recombinant viruses were then intranasally applied to ferrets, a species highly susceptible to Canine Distemper infection, to evaluate the safety and efficacy of the recombinant viruses. The ferrets were closely observed for clinical signs of distemper. Blood and tissue samples were taken at various time points post inoculation, and evaluated for the presence of recombinant virus and levels of immune responses elicited. The recombinant Canine Distemper Virus vector containing SIV Gag proved to be clinically safe when administered to a highly susceptible species. The recombinant virus was able to replicate in the host, and both humoral and cellular immune responses to the virus backbone as well as the insert were evident.