Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease

Abstract

Illustrates the study design of the CWD vaccination experiment. There were five vaccinated white-tailed deer and 6 vehicle controls. Deer were matched for Prnp genotype (95Q/96G/116A/138S/226Q), except two deer in both the control and vaccinated group had the most common polymorphism (∼26% of deer) that confers partial resistance to CWD infection, codon 96 G/S instead of 96 G/G. •We have developed a Salmonella vaccine strain that expresses cervid PrP.•The Salmonella vaccine has been tested in white tailed deer.•The vaccine induced a mucosal and systemic response to cervid PrP and PrPCWD.•Vaccinated deer had partial protection for chronic wasting disease.•This is the first partially effective vaccine for a prion disease. Prion disease is a unique category of illness, affecting both animals and humans, in which the underlying pathogenesis is related to a conformational change of a normal, self-protein called PrPC (C for cellular) to a pathological and infectious conformer known as PrPSc (Sc for scrapie). Bovine spongiform encephalopathy (BSE), a prion disease believed to have arisen from feeding cattle with prion contaminated meat and bone meal products, crossed the species barrier to infect humans. Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CWD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days p=0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrPCWD. We document the first partially successful vaccination for a prion disease in a species naturally at risk.