Dataset Information

Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (Mustela nigripes) and Their Susceptibility to Viral Challenge.

ABSTRACT: A preliminary vaccination trial against the emergent pathogen, SARS-CoV-2, was completed in captive black-footed ferrets (Mustela nigripes; BFF) to assess safety, immunogenicity, and anti-viral efficacy. Vaccination and boosting of 15 BFF with purified SARS-CoV-2 S1 subunit protein produced a nearly 150-fold increase in mean antibody titers compared to pre-vaccination titers. Serum antibody responses were highest in young animals, but in all vaccinees, antibody response declined rapidly. Anti-viral activity from vaccinated and unvaccinated BFF was determined in vitro, as well as in vivo with a passive serum transfer study in mice. Transgenic mice that received BFF serum transfers and were subsequently challenged with SARS-CoV-2 had lung viral loads that negatively correlated (p < 0.05) with the BFF serum titer received. Lastly, an experimental challenge study in a small group of BFF was completed to test susceptibility to SARS-CoV-2. Despite viral replication and shedding in the upper respiratory tract for up to 7 days post-challenge, no clinical disease was observed in either vaccinated or naive animals. The lack of morbidity or mortality observed indicates SARS-CoV-2 is unlikely to affect wild BFF populations, but infected captive animals pose a potential risk, albeit low, for humans and other animals.

SUBMITTER: Leon AE

PROVIDER: S-EPMC9612080 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (<i>Mustela nigripes</i>) and Their Susceptibility to Viral Challenge.

Leon Ariel E AE Garelle Della D Hartwig Airn A Falendysz Elizabeth A EA Ip Hon S HS Lankton Julia S JS Tretten Tyler N TN Spraker Terry R TR Bowen Richard R Rocke Tonie E TE

Viruses 20221004 10

A preliminary vaccination trial against the emergent pathogen, SARS-CoV-2, was completed in captive black-footed ferrets (Mustela nigripes; BFF) to assess safety, immunogenicity, and anti-viral efficacy. Vaccination and boosting of 15 BFF with purified SARS-CoV-2 S1 subunit protein produced a nearly 150-fold increase in mean antibody titers compared to pre-vaccination titers. Serum antibody responses were highest in young animals, but in all vaccinees, antibody response declined rapidly. Anti-vi ...[more]

PMID: 36298743

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Project description:In recent years, the ex situ population of the endangered black-footed ferret (Mustela nigripes; ferret) has experienced a decline in normal sperm morphology (from 50% to 20%), which may be linked to inbreeding depression and/or a dietary change. We examined the effects of adding carcass and vitamin E to the diet on stress and reproductive biomarkers in male ferrets (n = 42 males including 16 juveniles and 26 adults) housed at the U.S. Fish and Wildlife National Black-footed Ferret Conservation Center (Carr, CO, USA). Fecal samples (3x/week) were collected from November and December (pre-breeding season, no diet change), February through May (breeding season, diet change) and June (post-breeding season, diet change) and analyzed for fecal glucocorticoid metabolites (FGM) via a corticosterone enzyme immunoassay (EIA). A subset of samples from adult males (n = 15) were analyzed for fecal androgen metabolites (FAM) via a testosterone EIA. We first used a linear mixed effects model to identify the important fixed effects among meat treatment, vitamin E treatment, age class (juvenile or adult), and all possible interactions on each hormone. We then examined the important factor's effects across seasons using the non-parametric Friedman test. We found that age did not influence (p = 0.33) FGMs; however there was a significant effect of meat treatment on FGM (p = 0.04) and an effect of vitamin E on FAMs (p<0.10). When fed carcass, FGMs declined (p<0.001) from pre- to the during the breeding season time period, but was similar (p>0.05) between during and post-breeding season periods. Males that were not fed carcass had higher (p<0.05) FGMs during the breeding season compared to pre- and post-breeding season and FGMs were lower (p<0.05) in the post-breeding season compared to pre-breeding season. Males fed with carcass had lower (p<0.001) FGM than males that were not fed carcass during both the pre-breeding and the breeding season but not during the post-breeding season (p>0.05). Males supplemented with vitamin E had higher (p<0.001) FAM than non-supplemented males during the breeding season only. For both groups, FAM was highest (p<0.05) during the breeding season. In conclusion, adding carcass to the diet can reduce glucocorticoid production and adding vitamin E can increase testosterone during the breeding season, which may influence reproductive success.

Project description:The plague bacterium Yersinia pestis is lethal to endangered black-footed ferrets (Mustela nigripes, BFF) and the prairie dogs (Cynomys spp., PD) on which they depend for habitat and prey. We assessed the effectiveness of an oral sylvatic plague vaccine delivered in baits to black-tailed PD (Cynomys ludovicianus, BTPD) from 2013 to 2017 on the Charles M. Russell National Wildlife Refuge (CMR) in northcentral Montana. We permanently marked BTPD on four paired vaccine (N = 1,349 individuals) and placebo plots (N = 926; 7,027 total captures). We analyzed capture-recapture data under a Cormack-Jolly-Seber model to estimate annual apparent survival. Overall, survival averaged 0.05 lower on vaccine plots than on paired placebo plots. Immediately before noticeable die-offs and detecting plague on pairs CMR1 and CMR2, 89% of BTPD sampled on vaccine plots had consumed at least one bait and the immune systems (pleural) of 40% were likely boosted by consuming baits over multiple years. Survival to the following year was 0.16 and 0.05 on the vaccine plots and 0.19 and 0.06 on the placebo plots for pairs CMR1 and CMR2, respectively. These rates were markedly lower than 0.63, the overall average estimate on those same plots during the previous 3 years. PD populations subjected to such large die-offs would not be expected to sustain a BFF population. An overriding limitation to achieving sufficient protection rests with vaccine delivery constraints. Late summer/fall bait distribution results in the highest bait uptake rates. However, the PD birth pulse each spring can double the size of populations in most years, greatly reducing the proportion of vaccinates in populations and diminishing potential herd immunity benefits. In addition to nonvaccinated juveniles and PD that do not consume bait, incomplete vaccine protection and time required for immunity to develop leaves a large majority of PD populations vulnerable to plague for 6-7 months or more each year.

Project description:The black-footed ferret (Mustela nigripes) is an endangered North American mustelid. This species is bred in managed care with the goal of reestablishing wild populations. However, individual ferrets in the conservation breeding programme have variable reproductive success. We monitored faecal steroid hormone metabolite profiles of 22 black-footed ferrets across two breeding seasons to examine whether endocrine factors were associated with successful reproduction. Among successfully whelping females, faecal progesterone metabolite concentrations were higher (P = 0.04) and faecal cortisol metabolite (FCM) concentrations were marginally higher (P = 0.07) in the late luteal phase compared to females who did not whelp (likely pseudopregnant). Effect sizes suggested that, in successfully whelping females, faecal oestradiol metabolite levels were higher in the follicular phase and FCM levels lower in the early luteal phase, but with high variation and lack of statistical significance. We speculate that this variation may be because male causes of reproductive failure account for some of these cases of pseudopregnancy. Among males, individuals that failed to successfully copulate had lower faecal testosterone metabolite concentrations than successful sires (P = 0.01). However, males who copulated but failed to sire a litter did not differ from successful sires in testosterone metabolite concentrations. Comparisons of sperm morphology between successful and unsuccessful sires were statistically underpowered, hence poor sperm quality could not be ruled out as a possible cause of these post-copulatory reproductive failures. Our data suggest that individuals who fail to reproduce in managed care are not experiencing chronic stress, based on FCM levels, although changes in females during the early luteal phase warrant further investigation. While male post-copulatory reproductive failure was not associated with deficiencies in sex hormone production, males that fail to copulate could potentially be targeted for testosterone supplementation.

Dataset Information

Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (Mustela nigripes) and Their Susceptibility to Viral Challenge.

Publications

Immunogenicity, Safety, and Anti-Viral Efficacy of a Subunit SARS-CoV-2 Vaccine Candidate in Captive Black-Footed Ferrets (<i>Mustela nigripes</i>) and Their Susceptibility to Viral Challenge.

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