OK. So no need to get all excited yet. This is just the tip of the iceberg and the long and arduous journey remains. Prion diseases are notorious for not having any known, effective treatment or preventive measures. So, even this weakly successful venture in animals is some hope in this rather niche field. Investigators at the New York University School of Medicine have developed a weakly successful vaccine against Chronic Wasting Disease (CWD) in white-tailed deer. CWD is a prion disease which is common in cervids and can cause progressive, irreversible degeneration and death. Though I could not locate any evidence of this disease making the species jump like bovine spongiform encephalitis did, the authors contend that given the large numbers of deer and elk suffering from this disease, there is a possible risk for human infection as well.
In this study, the investigators comment in the abstract:
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.
To be honest it does not seem like anything to make a big deal out of yet, but there is some progress, and that cannot be totally discounted. The same group had previously showed that there was successful induction of mucosal immunity in mice based on a similar approach.
Using attenuated strains of Salmonella to mimic the process of natural inoculation with prion proteins sounds like a clever plan to avoid toxicity and development of tolerance to the vaccine strains in the vaccinated animals.
However, there is limited reason to rejoice because though these results are promising, an effective vaccine for man is still some distance away. While it is well known that successful interventions and experimentation in animals does not always translate into similar exciting results in human trials for a multitude of results, the current study results are also not very successful in animal models. All they have done, in my opinion, is to determine with some certainty that the oral route using a Salmonella vehicle to transport the prion expressing genetic code is a viable avenue that demands more attention. Effect wise, this vaccine, much like the mouse prion protein expressing experiment, has succeeded to only delay the onset of the disease and not entirely prevent it (save for the one deer at follow up).
However, considering the dearth of options in this field, even this is a lot of good news. This approach of passing prion protein genes in attenuated bacteria to create an immune reaction could be the way to look at newer approaches to vaccines against prion diseases.
1.Goñi, F., Mathiason, C., Yim, L., Wong, K., Hayes-Klug, J., Nalls, A., Peyser, D., Estevez, V., Denkers, N., Xu, J., Osborn, D., Miller, K., Warren, R., Brown, D., Chabalgoity, J., Hoover, E., & Wisniewski, T. (2015). Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease Vaccine, 33 (5), 726-733 DOI: 10.1016/j.vaccine.2014.11.035
2. Goñi F, Knudsen E, Schreiber F, Scholtzova H, Pankiewicz J, Carp R, Meeker HC, Rubenstein R, Brown DR, Sy MS, Chabalgoity JA, Sigurdsson EM, Wisniewski T. Mucosal vaccination delays or prevents prion infection via an oral route. Neuroscience. 2005;133(2):413-21. PubMed PMID: 15878645.
Categories: Infectious Diseases