Entwicklung eines Nanopartikel-basierenden Impfstoffes zur Prävention von akuten und wiederkehrenden Herpes Simplex Virus Infektionen
Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
Zusammenfassung der Projektergebnisse
Herpes simplex viruses 1 and 2 are among the most ubiquitous human infections and persist lifelong in the host after primary infection. Recurrence of HSV infections contributes to painful lesions in the orofacial (cold scores) or genital area. Usually, recurrent infections are painful but self-limiting. In contrast, serious complications can be observed in individuals suffering from ocular infections in immunocompromized patients with generalized infections affecting the central nervous system, or in newborns who became infected during pregnancy. There are no licensed vaccines currently available for the prevention or treatment of HSV-1/2 infections. Numerous attempts to develop such a vaccine have been undertaken thus far, but have not led to success. Due to the persisting need for a protective vaccine, the aim of the present study was to develop a nanoparticle-based vaccine which can induce cell-to-cell spread inhibiting antibodies thereby protecting from HSV-disease. Upon primary infection or reactivation from ganglia, the viruses spread by direct cell-cell contacts and thus escape from the host immune response. We have developed a monoclonal antibody (mAb 2c) which inhibits the HSV cell-to-cell spread, thereby protecting from lethal genital infection and blindness in the corresponding animal models. In the present study we have designed a nanoparticle-based vaccine to induce protective antibody responses exceeding the cell-to-cell spread inhibiting properties of mAb 2c. We used biodegradable calcium phosphate (CaP) nanoparticles coated with a synthetic peptide that represents the conformational epitope on HSV-1/2 gB recognized by mAb 2c. The peptideloaded CaP-nanoparticles additionally contained a TLR-ligand CpGm and were formulated with the GlaxoSmithKline AS04 adjuvant system to facilitate the humoral immune response. Mice immunized three times every two weeks with the peptide-loaded CaP-nanoparticle vaccine showed antibody responses with cell-to-cell spread inhibiting properties. Two weeks after the last immunization, the mice were challenged with a lethal dose of HSV-1 and observed over a period of 30 days. In contrast to mock-immunized mice, mice immunized with the peptide-loaded CaP-nanoparticle vaccine showed reduced viral loads at the vaginal mucosa and nearly completely survived the HSV-1 infection. In conclusion, we have developed a CaP-nanoparticle-based vaccine that effectively protected mice from lethal HSV-1 infection by inducing cell-to-cell spread antibodies.
Projektbezogene Publikationen (Auswahl)
- Role of L-particles during herpes simplex virus infection. Frontiers in Microbiology (2017)
Christiane Silke Heilingloh and Adalbert Krawczy
(Siehe online unter https://doi.org/10.3389/fmicb.2017.02565) - Antiviral human antibodies from combinatorial phage display libraries. In: Antibody Engineering (2018), ISBN 978-953-51-5294-1
Philipp Diebolder and Adalbert Krawczyk
(Siehe online unter https://doi.org/10.5772/intechopen.70139)
