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USGS2022

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

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.

Viruses↗

USGS2014

Season and application rates affect vaccine bait consumption by prairie dogs in Colorado and Utah, USA

Plague, a zoonotic disease caused by the bacterium Yersinia pestis , causes high rates of mortality in prairie dogs ( Cynomys spp.). An oral vaccine against plague has been developed for prairie dogs along with a palatable bait to deliver vaccine and a biomarker to track bait consumption. We conducted field trials between September 2009 and September 2012 to develop recommendations for bait distribution to deliver plague vaccine to prairie dogs. The objectives were to evaluate the use of the biomarker, rhodamine B, in field settings to compare bait distribution strategies, to compare uptake of baits distributed at different densities, to assess seasonal effects on bait uptake, and to measure bait uptake by nontarget small mammal species. Rhodamine B effectively marked prairie dogs' whiskers during these field trials. To compare bait distribution strategies, we applied baits around active burrows or along transects at densities of 32, 65, and 130 baits/ha. Distributing baits at active burrows or by transect did not affect uptake by prairie dogs. Distributing baits at rates of ≥65/ha (or ≥1 bait/active burrow) produced optimal uptake, and bait uptake by prairie dogs in the autumn was superior to uptake in the spring. Six other species of small mammals consumed baits during these trials. All four species of tested prairie dogs readily consumed the baits, demonstrating that vaccine uptake will not be an obstacle to plague control via oral vaccination.

Colorado, Utah↗

USGS2014

Managing prairie dogs by managing plague: a vaccine for the future?

The Black-footed Ferret Recovery Implementation Team Executive Committee is conducting a project to develop, and (hopefully) eventually implement, a plague vaccination program for prairie dogs. The project is a component of the Western Association of Fish and Wildlife Agencies Grasslands Conservation Initiative. An effective, field-worthy vaccine against plague could be the biggest breakthrough in recovery efforts for the black-footed ferret since the 1981 rediscovery of wild ferrets near Meeteetse, Wyoming. If proven efficacious, the vaccine could help agencies and stakeholder cooperators maintain specific populations of prairie dogs at robust levels, thus enhancing range-wide conservation of those species, as well recovery of the ferret, while enabling control of other prairie dog populations to resolve site-specific agricultural and human health concerns. The results of laboratory and field-testing in the early stages of developing this vaccine are preliminary but mostly encouraging. A plan for broad-scale application is being developed for possible use when testing has been completed and (if warranted) the vaccine is registered for governmental use. An overview of all aspects of the project is discussed.

Conference Paper↗

USGS2006

Immunogenicity and efficacy of three recombinant subunit Pasteurella multocida toxin vaccines against progressive atrophic rhinitis in pigs

Three short fragments of recombinant subunit Pasteurella multocida toxin (rsPMT) were constructed for evaluation as candidate vaccines against progressive atrophic rhinitis (PAR) of swine. PMT-specific antibody secreting cells and evidence of cellular immunity were detected in rsPMT-immunized pigs following authentic PMT challenge or homologous antigen booster. Piglets immunized with rsPMT fragments containing either the N-terminal or the C-terminal portions of PMT developed high titers of neutralizing antibodies. Pregnant sows immunized with rsPMT had higher levels of maternal antibodies in their colostrum than did those immunized with a conventional PAR-toxoid vaccine. Offspring from rsPMT vaccinated sows had better survival after challenge with a five-fold lethal dose of authentic PMT and had better growth performance after challenge with a sublethal dose of toxin. Our findings indicate these non-toxic rsPMT proteins are attractive candidates for development of a subunit vaccine against PAR in pigs.

Vaccine↗

USGS2014

A recombinant raccoon poxvirus vaccine expressing both Yersinia pestis F1 and truncated V antigens protects animals against lethal plague.

In previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses ( r RCN) expressing Yersinia pestis antigens (F1 and V307-a truncated version of the V protein) provided superior protection against plague challenge compared to individual single antigen constructs. To reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (SPV) control program for prairie dogs, a dual antigen construct is more desirable. Here we report the construction and characterization of a novel RCN-vectored vaccine that simultaneously expresses both F1 and V307 antigens. This dual antigen vaccine provided similar levels of protection against plague in both mice and prairie dogs as compared to simultaneous administration of the two single antigen constructs and was also shown to protect mice against an F1 negative strain of Y. pestis. . The equivalent safety, immunogenicity and efficacy profile of the dual RCN-F1/V307 construct warrants further evaluation in field efficacy studies in sylvatic plague endemic areas.

Vaccines↗

USGS2022

Evaluation of Francisella orientalis ΔpdpA as a live attenuated vaccine against piscine Francisellosis in Nile tilapia

Francisella orientalis is an important bacterial pathogen of marine and freshwater fish with worldwide distribution. Fish francisellosis is a severe subacute to chronic granulomatous disease, with high mortalities and high infectivity rates in cultured and wild fish. To date, there is no approved vaccine for this disease. In this study, we evaluated the efficacy of a defined F. orientalis pathogenicity determinant protein A ( pdpA ) mutant (Δ pdpA ) as a live attenuated immersion vaccine against subsequent immersion challenge with the wild-type organism. Immunized Nile tilapia Oreochromis niloticus were protected (45% relative percent survival) from the lethal challenges and presented significantly lower mortality than nonvaccinated and challenged treatments. Although serum IgM was significantly higher in immunized fish, similar bacterial loads were detected in vaccinated and nonvaccinated survivors. In conclusion, although the F. orientalis Δ pdpA is attenuated and effectively stimulated an adaptive immune response, the low relative percent survival and high bacterial persistence in survivors of immunized and challenged treatments indicates low suitability of Δ pdpA as a mucosal vaccine for tilapia under conditions used in this study.

Journal of Aquatic Animal Health↗

USGS2017

Vaccine effects on heterogeneity in susceptibility and implications for population health management

Heterogeneity in host susceptibility is a key determinant of infectious disease dynamics but is rarely accounted for in assessment of disease control measures. Understanding how susceptibility is distributed in populations, and how control measures change this distribution, is integral to predicting the course of epidemics with and without interventions. Using multiple experimental and modeling approaches, we show that rainbow trout have relatively homogeneous susceptibility to infection with infectious hematopoietic necrosis virus and that vaccination increases heterogeneity in susceptibility in a nearly all-or-nothing fashion. In a simple transmission model with an R 0 of 2, the highly heterogeneous vaccine protection would cause a 35 percentage-point reduction in outbreak size over an intervention inducing homogenous protection at the same mean level. More broadly, these findings provide validation of methodology that can help to reduce biases in predictions of vaccine impact in natural settings and provide insight into how vaccination shapes population susceptibility.

mBio↗

USGS1979

Immersion vaccination of sockeye salmon (Oncorhynchus nerka) with two pathogenic strains of Vibrio anguillarum

Sockeye salmon ( Oncorhynchus nerka ) were immersion-vaccinated in suspensions containing 5&ensp;×&ensp;10 7 , 5&ensp;×&ensp;10 6 , 5&ensp;×&ensp;10 5 , or 5&ensp;×&ensp;10 4 bacteria/mL of bivalent or monovalent, formalin-killed Vibrio anguillarum , Types I and II. The fish were split into two lots and held for 54&ensp;d. At that time one lot was challenged with living, virulent V . anguillarum , Type I, and one with living, virulent V . anguillarum , Type II. Immunization with bivalent bacterin effectively protected the fish from vibriosis, but monovalent vaccine was effective only against the homologous challenge. Immunization with the highest concentration of Type I monovalent bacterin resulted in 0% Type I and 58% Type II challenge mortality. Immunization with the highest concentration of Type II monovalent bacterin resulted in 41% Type I and 0% Type II challenge mortality. Immunization with the highest concentration of bivalent Type I/Type II bacterin resulted in 2% mortality in both challenges. Protective bacterins were effective at concentrations down to 5&ensp;×&ensp;10 5 bacteria/mL. Key words : immersion vaccination, bivalent vaccines, Vibrio anguillarum , vibriosis.

Journal of the Fisheries Research Board of Canada↗

USGS2014

A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1] , the case-fatality ratio of measles [2] , and the probability of infection and, given infection, of symptoms in cholera [3] . Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4] . These distributions can be distinguished in vaccine field trials from the time dependence of infections [5] . Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6] , [7] , although the results are not comparable across regions unless there is explicit control for baseline transmission [8] . Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9] – [11] and natural settings [12] , [13] . These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health.

PLoS Pathogens↗

USGS2021

Modeling of future COVID-19 cases, hospitalizations, and deaths, by vaccination rates and nonpharmaceutical intervention scenarios — United States, April–September 2021

What is already known about this topic? Increases in COVID-19 cases in March and early April occurred despite a large-scale vaccination program. Increases coincided with the spread of SARS-CoV-2 variants and relaxation of nonpharmaceutical interventions (NPIs). What is added by this report? Data from six models indicate that with high vaccination coverage and moderate NPI adherence, hospitalizations and deaths will likely remain low nationally, with a sharp decline in cases projected by July 2021. Lower NPI adherence could lead to substantial increases in severe COVID-19 outcomes, even with improved vaccination coverage. What are the implications for public health practice? High vaccination coverage and compliance with NPIs are essential to control COVID-19 and prevent surges in hospitalizations and deaths in the coming months.

Morbidity and Mortality Weekly Report↗

USGS2011

Simulating sterilization, vaccination, and test-and-remove as brucellosis control measures in bison

Brucella abortus, the causative agent of bovine brucellosis, infects wildlife, cattle, and humans worldwide, but management of the disease is often hindered by the logistics of controlling its prevalence in wildlife reservoirs. We used an individually based epidemiological model to assess the relative efficacies of three management interventions (sterilization, vaccination, and test-and-remove). The model was parameterized with demographic and epidemiological data from bison in Yellowstone National Park, USA. Sterilization and test-and-remove were most successful at reducing seroprevalence when they were targeted at young seropositive animals, which are the most likely age and sex category to be infectious. However, these approaches also required the most effort to implement. Vaccination was less effective (even with a perfect vaccine) but also required less effort to implement. For the treatment efforts we explored (50–100 individuals per year or 2.5–5% of the female population), sterilization had little impact upon the bison population growth rate when selectively applied. The population growth rate usually increased by year 25 due to the reduced number of Brucella-induced abortions. Initial declines in seroprevalence followed by rapid increases (>15% increase in 5 years) occurred in 3–13% of simulations with sterilization and test-and-remove, but not vaccination. We believe this is due to the interaction of superspreading events and the loss of herd immunity in the later stages of control efforts as disease prevalence declines. Sterilization provided a mechanism for achieving large disease reductions while simultaneously limiting population growth, which may be advantageous in some management scenarios. However, the field effort required to find the small segment of the population that is infectious rather than susceptible or recovered will likely limit the utility of this approach in many free-ranging wildlife populations. Nevertheless, we encourage scientists and policy makers to consider sterilization as part of a suite of available brucellosis management tools.

Ecological Applications↗

USGS2012

Sylvatic plague vaccine and management of prairie dogs

Scientists at the USGS National Wildlife Health Center (NWHC), in collaboration with colleagues at the University of Wisconsin (UW), have developed a sylvatic plague vaccine that shows great promise in protecting prairie dogs against plague (Mencher and others, 2004; Rocke and others, 2010). Four species of prairie dogs reside in the United States and Canada, and all are highly susceptible to plague and regularly experience outbreaks with devastating losses. Along with habitat loss and poisoning, plague has contributed to a significant historical decline in prairie dog populations. By some estimates, prairie dogs now occupy only 1 to 2 percent of their former range (Proctor and others, 2006), with prairie dog colonies being now much smaller and fragmented than they were historically, making individual colonies more vulnerable to elimination by plague (Antolin and others, 2002). At least one species, the Utah prairie dog ( Cynomys parvidens ) is listed by the U.S. Fish and Wildlife Service (FWS) as "threatened." Controlling plague is a vital concern for ongoing management and conservation efforts for prairie dogs. Current efforts to halt the spread of plague in prairie dog colonies typically rely on dusting individual prairie dog burrows with pesticides to kill plague-infected fleas. Although flea-control insecticides, such as deltamethrin, are useful in stopping plague outbreaks in these prairie dog colonies, dusting of burrows is labor intensive and time consuming and may affect other insects and arthropods. As an alternative approach, NWHC and UW scientists developed a sylvatic plague vaccine (SPV) for prairie dogs that can be delivered via oral bait. Laboratory studies have shown that consumption of this vaccine-laden bait by different prairie dog species results in significant protection against plague infection that can last for at least 9 months (Rocke and others, 2010; Rocke, unpublished). Work has now shifted to optimizing baits and distribution methods for field delivery of the vaccine. Ultimately, the bait will be formulated in a size and shape that facilitates distribution by plane or overland vehicle. Field studies to assess the safety and efficacy of SPV are being planned. These studies will require involvement from numerous partners, including state and federal land management agencies, tribal organizations, private landowners and non-government agencies.

Fact Sheet↗

USGS2011

Use of Rhodamine B as a biomarker for oral plague vaccination of prairie dogs

Oral vaccination against Yersinia pestis could provide a feasible approach for controlling plague in prairie dogs ( Cynomys spp.) for conservation and public health purposes. Biomarkers are useful in wildlife vaccination programs to demonstrate exposure to vaccine baits. Rhodamine B (RB) was tested as a potential biomarker for oral plague vaccination because it allows nonlethal sampling of animals through hair, blood, and feces. We found that RB is an appropriate marker for bait uptake studies of C. ludovicianus) when used at concentrations <0.5% of bait mass dosed to deliver >10 mg RB per kg target animal mass. Whiskers with follicles provided the best sample for RB detection.

Journal of Wildlife Diseases↗

USGS2005

Development of a subunit vaccine for infectious pancreatic necrosis virus using a baculovirus insect/larvae system

Various attempts to develop a vaccine against infectious pancreatic necrosis virus (IPNV) have not yielded consistent results. Thus, at present, no commercial vaccine is available that can be used with confidence to immunize fry of salmon and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp strain and expressed all structural protein genes in insect cells and larvae using a baculovirus expression system. Green fluorescent protein was also co-expressed as a reporter molecule. High yields of IPNV proteins were obtained and the structural proteins self assembled to form virus-like particles (VLPs). We tested the immunogenicity of the putative VLP antigen in immersion vaccine experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using an oil adjuvant formulation. Rainbow trout were challenged by immersion using either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination, while Atlantic salmon were bath challenged with Sp strain after two months, after parr-smolt transformation. In the rainbow trout fry challenged two weeks post-immunization, cumulative mortality rates three weeks post challenge were 14 % in the fry that had received the highest dose versus 8 % in the control groups. No indication of protection was seen in repeated trials using a lower dose of antigen and challenge three weeks post-immunisation. The cumulative mortality rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post challenge was lower (56 %) than in the control fish (77 %), showing a dose-response pattern.

Conference Paper↗

USGS2007

Pathophysiology of white-tailed deer vaccinated with porcine zona pellucida immunocontraceptive

White-tailed deer (n = 14 treated, n = 7 control) were examined postmortem to identify any possible pathophysiology resulting from PZP immunocontraception vaccination. Deer were treated twice in 1997; given a booster in 1998, with six being revaccinated in September 2000. Granulomas were found at injection sites of most deer, even 2 years post-treatment. Eosinophilic oophoritis occurred in 6 of 8 (75%) deer vaccinated in 1998, and 3 of 6 (50%) revaccinated in 2000. The 2000 revaccinates without oophoritis, had significantly fewer normal secondary follicles than control females (P = 0.03), and deer in the1998 treatment group (P = 0.04). PZP immunocontraceptive vaccine elicited ovarian pathologies in deer similar to those observed in other species. ?? 2007 Elsevier Ltd. All rights reserved.

Vaccine↗

USGS2024

Density estimation using spatial capture-recapture analyses: Application to vaccination of prairie dogs against sylvatic plague

Prairie dogs are notoriously difficult to enumerate, with previously methods including visual counts, mark-resight, burrow counts, and catch per unit effort. Unlike those methods, spatial capture-recapture (SCR) analyses allow for formal estimation of density along with associated estimates of uncertainty, detection probability, and the size of the average area over which an individual was detected during the study period (referred to as an activity center). Using SCR analyses, we compared density estimates as part of a field trial evaluating the effectiveness of an oral sylvatic plague vaccine in black-tailed prairie dogs ( Cynomys ludovicianus ), Gunnison's prairie dogs ( C. gunnisoni ), white-tailed prairie dogs ( C. leucurus ), and Utah prairie dogs ( C. parvidens ) at 11 study areas in the western United States. The study was designed as a matched pairs analysis that included 27 individual paired plots (54 plots), each consisting of a plot treated with vaccine baits and a plot treated with placebo baits. Overall, we captured >3,000 individuals each year on these plots, and recapture rates ranged from 5–87%. For black-tailed prairie dogs, density estimates ranged from 2.7 individuals/ha (95% CI = 2.2–3.3/ha) to 77.3/ha (63.2–94.4/ha), and for Gunnison's prairie dogs, estimates ranged from 11.7/ha (10.6–12.8/ha) to 15.4/ha (14.4–16.7/ha). White-tailed prairie dogs were at their lowest density (3.3/ha, 95% CI = 2.9–3.8/ha) during the first year of the study and their highest density (14.5/ha; 13.5–15.6/ha) during the last year of the study. Utah prairie dog density estimates ranged from a low of 4.0/ha (95% CI = 3.55–4.6/ha) to a high of 20.8/ha (16.8–25.8/ha). Best-fitting models of prairie dog density indicated increasing patterns of density over time on most study plots, negative effects of plague, and positive effects of vaccination. Finally, we found low correlations between catch per unit effort estimates from previous published literature at these sites and our densities estimates. Spatial capture-recapture estimates allowed us to consistently compare treatment effects across space and time, although some exceptions are noted where we observed significant movement between plots within a pair (3 pairs) and when trapping effort between plots or years was not consistent.

Arizona, Colorado, Montana, South Dakota, Utah, Wy↗

USGS2016

Evaluating a strategy to deliver vaccine to white-tailed deer at a landscape level

Effective delivery of vaccines and other pharmaceuticals to wildlife populations is needed when zoonotic diseases pose a risk to public health and natural resources or have considerable economic consequences. The objective of our study was to develop a bait-distribution strategy for potential delivery of oral bovine tuberculosis (bTB) vaccine to white-tailed deer ( Odocoileus virginianus ) where deer are reservoirs for the disease. During 17 February and 2 March 2011, we created a grid of experimental bait stations ( n  = 64) on Sandhill Wildlife Management Area, Wisconsin, USA, to assess station densities needed to attract and deliver placebo baits to free-ranging white-tailed deer and look for associations among deer density, number of bait stations per deer, and bait consumption. We placed 1 L of commercially available alfalfa cubes at bait stations 652 m apart, and monitored stations with motion-activated cameras for 5 days to document visitation and consumption by deer and nontarget species. Deer discovered 38% of all bait stations within 37 hr, on average (SE = 3.91 hr), and consumed variable amounts of bait at each station. Deer were documented in 94% of all photographs of wildlife at bait stations. We found no correlation between bait consumption and deer density or the number of bait stations per deer. We provide the first information on use of baits by free-ranging deer and nontarget wildlife to eventually vaccinate deer against bTB at a landscape level. The results of this study can further the development of strategies in delivery of pharmaceuticals to free-ranging white-tailed deer.

Wildlife Society Bulletin↗

USGS1978

Spray vaccination: A method for the immunization of fish

An economical, efficacious vaccine delivery system for immunizing fish has been developed which employs a liquid spray apparatus operated at pressures up to 7.0 kg/cm 2 (0 to 100 lb/in 2 ). A bacterin consisting of formalin-killed Vibrio anguillarum culture was both antigenic and immunogenic when sprayed on coho salmon(Oncorhynchus kisutch)and rainbow trout(Salmo gairdneri). The technique, referred to as spray(shower)vaccination, was found to confer higher levels of immunity against virulent V. anguillarum than oral vaccination.

Fish Pathology↗