Virally-vectored vaccine candidates against white-nose syndrome induce anti-fungal immune response in little brown bats (Myotis lucifugus)

Abstract

White-nose syndrome (WNS) caused by the fungus, Pseudogymnoascus destructans ( Pd ) has killed millions of North American hibernating bats. Currently, methods to prevent the disease are limited. We conducted two trials to assess potential WNS vaccine candidates in wild-caught Myotis lucifugus . In a pilot study, we immunized bats with one of four vaccine treatments or phosphate-buffered saline (PBS) as a control and challenged them with Pd upon transfer into hibernation chambers. Bats in one vaccine-treated group, that received raccoon poxviruses (RCN) expressing Pd calnexin (CAL) and serine protease (SP), developed WNS at a lower rate (1/10) than other treatments combined (14/23), although samples sizes were small. The results of a second similar trial provided additional support for this observation. Bats vaccinated orally or by injection with RCN-CAL and RCN-SP survived Pd challenge at a significantly higher rate (P = 0.01) than controls. Using RT-PCR and flow cytometry, combined with fluorescent in situ hybridization, we determined that expression of IFN-γ transcripts and the number of CD4 + T-helper cells transcribing this gene were elevated (P < 0.10) in stimulated lymphocytes from surviving vaccinees (n = 15) compared to controls (n = 3). We conclude that vaccination with virally-vectored Pd antigens induced antifungal immunity that could potentially protect bats against WNS.

Fluorescent biomarkers demonstrate prospects for spreadable vaccines to control disease transmission in wild bats

“…While the exact parameter estimates and models developed here should not be applied directly to other bat pathogens, the framework linking biomarkers to mathematical models can guide future research. For several bat pathogens of public health or conservation concern, such as white nose syndrome, Hendra virus and Marburg virus, epidemiological models have been proposed [44][45][46] , and vaccines for bats either exist or have precedents encouraging their development [47][48][49] . In these cases, our approach could be implemented over relatively short timescales to evaluate the prospects for vaccines to aid management and the immunological and epidemiological characteristics that would be required for success before investing resources in vaccine development.…”

Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture

“…Once established in the epizootic and established phases, management actions necessarily shift from limiting spread to reducing impacts on host populations. Options here include vaccination (109,110) or bioaugmentation with probiotics (107,111), manipulating habitats to favor the host over the pathogen, facilitated evolution or host-translocation of disease-resistant individuals, and ex situ conservation of highly threatened species. The safeguarding of threatened species through establishing ex situ captive breeding programs currently remains the only active conservation method to avoid species loss after invasion, and Amphibian Arks maintains the possibility for selective breeding or genetic modification of amphibians for resistance (112).…”

The Rise of Fungi: A Report on the CIFAR Program Fungal Kingdom: Threats & Opportunities Inaugural Meeting

“…Akin to the decimation of amphibian populations by B. dendrobatidis, there have been massive die offs in North American hibernating bat populations due to white-nose syndrome (WNS) caused by the introduction of a single clone of the fungus Pseudogymnoascus destructans (Trivedi et al 2017). Since its recent emergence in New York State in approximately 2006 (Blehert et al 2009), there has been substantial progress in understanding the etiology of WNS and developing vaccines with efficacy against P. destructans (Rocke et al 2019). David Blehert (U.S. Geological Survey National Wildlife Health Center) described the histopathologic criteria to confirm WNS in bats (Meteyer et al 2009) and proposed a multi-stage disease progression for WNS, linking wing tissue damage by P. destructans to morbidity and mortality (Warnecke et al 2013;Verant et al 2014).…”

“…Klein found that MyluK dectin-1 recognized A. redellii spores more strongly than P. destructans, indicating differences in the keratinocyte immune response to these two fungi. As a further effort to develop therapeutic interventions for bat WNS, Klein and others at the University of Wisconsin-Madison and the U.S. Geological Survey National Wildlife Health Center generated a vaccine with efficacy against P. destructans (Rocke et al 2019). Specifically, they found success with a vaccine that uses an attenuated raccoon poxvirus as a vector to express P. destructans calnexin and serine protease destructin-1 as immunogenic antigens (Rocke et al 2019).…”

“…As a further effort to develop therapeutic interventions for bat WNS, Klein and others at the University of Wisconsin-Madison and the U.S. Geological Survey National Wildlife Health Center generated a vaccine with efficacy against P. destructans (Rocke et al 2019). Specifically, they found success with a vaccine that uses an attenuated raccoon poxvirus as a vector to express P. destructans calnexin and serine protease destructin-1 as immunogenic antigens (Rocke et al 2019). Bats treated with this vaccine developed WNS at a lower rate (Rocke et al 2019), and work is ongoing to develop strategies for vaccine distribution.…”