P41.12
Background: Vesicular stomatitis virus (VSV) is a potent candidate vaccine vector for various diseases. However, VSV's inherent neurotoxicity has limited its clinical application. Additionally, VSV induces neutralizing antibodies rapidly and is thus ineffective upon repeated applications. Our group has recently shown that VSV pseudotyped with the glycoprotein (GP) of the lymphocytic choriomeningitis virus, VSV-GP, is not neurotoxic. Here, we evaluated the potential of VSV-GP as a vaccine vector.
Methods: We used Ovalbumin (OVA) as a model antigen and analyzed immunogenicity of GP-pseudotyped and wild-type VSV expressing OVA (VSV-GP-OVA and VSV-OVA) in vitro and in vivo in mouse models.
Results: Mouse experiments revealed that both VSV-OVA and VSV-GP-OVA induced functional OVA-specific CTLs and anti-OVA antibodies upon single immunization. However, boosting with the same vector was only possible for the GP-pseudotype but not for wild-type VSV. The efficacy of repeated immunization with VSV-OVA was most likely limited by the high levels of neutralizing antibodies, which we detected after the first immunization. In contrast, no neutralizing antibodies against VSV-GP were induced even after seven boost immunizations. CTL responses induced by VSV-GP-OVA were as potent as those induced by an adenoviral state-of-the-art vaccine vector. Additionally, immunization with both vectors completely protected mice from infection with Listeria monocytogenes expressing OVA.
Conclusions: Taken together, VSV-GP is non-neurotoxic, induces potent immune responses, enables boosting and thus is a promising novel vaccine vector.
