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At least 19 recordsLinked to original sources
USGS2024

Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub

Background Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). Methods and findings The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000–598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. Conclusions COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

PLOS Medicine↗
USGS2006

Introduction of translation stop condons into the viral glycoprotein gene in a fish DNA vaccine eliminates induction of protective immunity

A highly efficacious DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was mutated to introduce two stop codons to prevent glycoprotein translation while maintaining the plasmid DNA integrity and RNA transcription ability. The mutated plasmid vaccine, denoted pIHNw-G2stop, when injected intramuscularly into fish at high doses, lacked detectable glycoprotein expression in the injection site muscle, and did not provide protection against lethal virus challenge 7 days post-vaccination. These results suggest that the G-protein itself is required to stimulate the early protective antiviral response observed after vaccination with the nonmutated parental DNA vaccine.

Marine Biotechnology↗
USGS2009

Pathogenicity of West Nile virus and response to vaccination in sandhill cranes ( Grus canadensis ) using a killed vaccine

West Nile virus was introduced into the United States in the vicinity of New York, New York, USA in 1999. The virus has since killed large numbers of birds nationwide, especially, but not limited to, crows ( Corvus brachyrhinchos ). One sandhill crane ( Grus canadensis ) at the Bridgeport Zoo (Bridgeport, Connecticut, USA) reportedly died from West Nile virus, so sandhill cranes and endangered whooping cranes ( Grus americana ), both in the wild and in captive breeding colonies at United States Geological Service (USGS) Patuxent Wildlife Research Center (Laurel, Maryland, USA) were considered at risk. A killed vaccine in sandhill cranes was evaluated by vaccinating and then challenging these cranes with live West Nile virus. No sandhill cranes inoculated with the killed vaccine developed significant titers when compared with unvaccinated controls. No sandhill cranes inoculated with the vaccine and challenged with the virus died from West Nile virus infection. In addition, no unvaccinated challenged sandhill cranes died. However, 2 days postchallenge, vaccinated cranes had significantly less viremia (P < 0.05) than unvaccinated cranes. Seven days postchallenge vaccinated cranes had significantly less cloacal shedding of the virus (P < 0.05) than unvaccinated cranes and significantly less weight loss (P < 0.05) as compared with unvaccinated cranes. Vaccinated sandhill cranes developed significantly higher titers 14 days postchallenge and were viremic for shorter periods of time after challenge than unvaccinated individuals. Unvaccinated challenged cranes had glial cell aggregates in both the brain and brain stem areas, and this was not observed in vaccinated challenged cranes or in vaccinated unchallenged cranes.

Journal of Zoo and Wildlife Medicine↗
USGS2015

Age at vaccination may influence response to sylvatic plague vaccine (SPV) in Gunnison’s prairie dogs ( Cynomys gunnisoni )

Gunnison&rsquo;s prairie dogs ( Cynomys gunnisoni ) have been considered at greater risk from Yersinia pestis (plague) infection in the montane portion of their range compared to populations at lower elevations, possibly due to factors related to flea transmission of the bacteria or greater host susceptibility. To test the latter hypothesis and determine whether vaccination against plague with an oral sylvatic plague vaccine (SPV) improved survival, we captured prairie dogs from a C. g. gunnisoni or &ldquo;montane&rdquo; population and a C. g. zuniensis or &ldquo;prairie&rdquo; population for vaccine efficacy and challenge studies. No differences ( P = 0.63) were found in plague susceptibility in non-vaccinated animals between these two populations; however, vaccinates from the prairie population survived plague challenge at significantly higher rates ( P < 0.01) than those from the montane population. Upon further analysis, we determined that response to immunization was most likely associated with differences in age, as the prairie group was much younger on average than the montane group. Vaccinates that were juveniles or young adults survived plague challenge at a much higher rate than adults ( P < 0.01 and P = 0.02, respectively), but no difference ( P = 0.83) was detected in survival rates between control animals of different ages. These results suggest that host susceptibility is probably not related to the assumed greater risk from plague in the C. g. gunnisoni or &ldquo;montane&rdquo; populations of Gunnison&rsquo;s prairie dogs, and that SPV could be a useful plague management tool for this species, particularly if targeted at younger cohorts.

Colorado↗
USGS2016

Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat ( Tadarida brasiliensis )

Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat ( Tadarida brasiliensis ), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA- luc , RCN- luc ) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN- luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 x 10 4 PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.

Vaccine↗
USGS2005

Testing a West Nile virus vaccine in sandhill cranes (Grus canadensis)

Eight sandhill cranes (Grus canadensis) were vaccinated with a commercial equine West Nile virus vaccine (Fort Dodge Animal Health, Fort Dodge, Iowa, USA) at the USGS Patuxent Wildlife Research Center, Laurel, Maryland, USA. Three doses of the vaccine were given, the first dose (day 0) was followed by a second 21 days later and the third dose 7 days after the second day 28 after the first dose). All doses were 0.50 ml. In addition, 5 sandhill cranes were given injections of similar amounts of sterile water on the same schedule. Blood for complete blood counts, serum chemistries, and serological testing was collected at weekly intervals. Ten weeks after the first injection of the vaccine and 6 weeks after the last of the 3 injections of the vaccine, the cranes were shipped to the USGS National Wildlife Heath Center, Madison, Wisconsin, USA. After a two-week adjustment period, 11 of these cranes were injected intramuscularly with one mosquito dose of West Nile virus. Two of the vaccinated cranes were not challenged and acted as uninfected controls. One week post challenge the only abnormal findings were slight weight loss (average 6% loss since the time of challenge with West Nile virus) and elevated white blood cell counts (heterophilic leukocytosis). There were no deaths and no clinically ill cranes (unvaccinated or vaccinated cranes) among the 11 challenged birds. All cranes were euthanized 6 weeks post challenge, and necropsies were performed. Pre-challenge titers showed no titer response to the vaccinations. However, when challenged, vaccinated cranes developed titers more quickly (within 7-10 days), and were viremic and shed virus via the cloaca for a shorter period of time than the unvaccinated cranes (2-7 days for vaccinated cranes versus 2-10 days for unvaccinated cranes). No remarkable lesions were noted in any of the cranes during the necropsy examinations. Histopathological findings are available for only four of the cranes at this time. Three of those had mild to moderate encephalitis, myelitis, and myocarditis. Initial histopathological findings also indicated a difference in the lesions found in the brains of the vaccinated versus unvaccinated cranes. The fourth crane was a vaccinated unchallenged control that had none of the lesions described. We concluded, based on the findings of no adverse reactions and the higher titers and reduced viremia seen in the cranes, that, indeed, the vaccine is safe for use in cranes and can be effective in reducing the severity of a natural infection. We would recommend this vaccine for use in adult cranes. A companion study is looking at the safety and efficacy of the vaccine for crane chicks as young as 7-10 days of age and that will be reported at a later date.

Book chapter↗
USGS2017

A effective DNA vaccine against diverse genotype J infectious hematopoietic necrosis virus strains prevalent in China

Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In this study, a DNA vaccine, designated pIHNch-G, was constructed with the glycoprotein (G) gene of a Chinese IHNV isolate SD-12 (also called Sn1203) of genotype J. The minimal dose of vaccine required, the expression of the Mx-1 gene in the muscle (vaccine delivery site) and anterior kidney, and the titers of the neutralizing antibodies produced were used to evaluate the vaccine efficacy. To assess the potential utility of the vaccine in controlling IHNV throughout China, the cross protective efficacy of the vaccine was determined by challenging fish with a broad range of IHNV strains from different geographic locations in China. A single 100 ng dose of the vaccine conferred almost full protection to rainbow trout fry (3 g) against waterborne or intraperitoneal injection challenge with IHNV strain SD-12 as early as 4 days post-vaccination (d.p.v.), and significant protection was still observed at 180 d.p.v. Intragenogroup challenges showed that the DNA vaccine provided similar protection to the fish against all the Chinese IHNV isolates tested, suggesting that the vaccine can be widely used in China. Mx-1 gene expression was significantly upregulated in the muscle tissue (vaccine delivery site) and anterior kidney in the vaccinated rainbow trout at both 4 and 7 d.p.v. Similar levels of neutralizing antibodies were determined with each of the Chinese IHNV strains at 60 and 180 d.p.v. This DNA vaccine should play an important role in the control of IHN in China.

Vaccine↗
USGS2008

DNA vaccine protects ornamental koi (Cyprinus carpio koi) against North American spring viremia of carp virus

The emergence of spring viremia of carp virus (SVCV) in the United States constitutes a potentially serious alien pathogen threat to susceptible fish stocks in North America. A DNA vaccine with an SVCV glycoprotein (G) gene from a North American isolate was constructed. In order to test the vaccine a challenge model utilizing a specific pathogen-free domestic koi stock and a cold water stress treatment was also developed. We have conducted four trial studies demonstrating that the pSGnc DNA vaccine provided protection in vaccinated fish against challenge at low, moderate, and high virus doses of the homologous virus. The protection was significant (p < 0.05) as compared to fish receiving a mock vaccine construct containing a luciferase reporter gene and to non-vaccinated controls in fish ranging in age from 3 to 14 months. In all trials, the SVCV-G DNA immunized fish were challenged 28-days post-vaccination (546 degree-days) and experienced low mortalities varying from 10 to 50% with relative percent survivals ranging from 50 to 88%. The non-vaccinated controls and mock construct vaccinated fish encountered high cumulative percent mortalities ranging from 70 to 100%. This is the first report of a SVCV DNA vaccine being tested successfully in koi. These experiments prove that the SVCV DNA (pSGnc) vaccine can elicit specific reproducible protection and validates its potential use as a prophylactic vaccine in koi and other vulnerable North American fish stocks.

Vaccine↗
USGS2022

A recombinant rabies vaccine that prevents viral shedding in rabid common vampire bats (Desmodus rotundus)

Vampire bat transmitted rabies (VBR) is a continuing burden to public health and agricultural sectors in Latin America, despite decades-long efforts to control the disease by culling bat populations. Culling has been shown to disperse bats, leading to an increased spread of rabies. Thus, non-lethal strategies to control VBR, such as vaccination, are desired. Here, we evaluated the safety and efficacy of a viral-vectored recombinant mosaic glycoprotein rabies vaccine candidate (RCN-MoG) in vampire bats ( Desmodus rotundus ) of unknown history of rabies exposure captured in México and transported to the United States. Vaccination with RCN-MoG was demonstrated to be safe, even in pregnant females, as no evidence of lesions or adverse effects were observed. We detected rabies neutralizing antibodies in 28% (8/29) of seronegative bats post-vaccination. Survival proportions of adult bats after rabies virus (RABV) challenge ranged from 55–100% and were not significantly different among treatments, pre- or post-vaccination serostatus, and route of vaccination, while eight pups (1–2.5 months of age) used as naïve controls all succumbed to challenge (P<0.0001). Importantly, we found that vaccination with RCN-MoG appeared to block viral shedding, even when infection proved lethal. Using real-time PCR, we did not detect RABV nucleic acid in the saliva samples of 9/10 vaccinated bats that succumbed to rabies after challenge (one was inconclusive). In contrast, RABV nucleic acid was detected in saliva samples from 71% of unvaccinated bats (10/14 sampled, plus one inconclusive) that died of the disease, including pups. Low seroconversion rates post-vaccination and high survival of non-vaccinated bats, perhaps due to earlier natural exposure, limited our conclusions regarding vaccine efficacy. However, our findings suggest a potential transmission-blocking effect of vaccination with RCN-MoG that could provide a promising strategy for controlling VBR in Latin America beyond longstanding culling programs.

San Luis Potosi↗
USGS2003

Evaluation of oral and subcutaneous delivery of an experimental canarypox recombinant canine distemper vaccine in the Siberian polecate (Mustela eversmanni)

We assessed the safety and efficacy of an experimental canarypox-vectored recombinant canine distemper virus (CDV) subunit vaccine in the Siberian polecat ( Mustela eversmanni ), a close relative of the black-footed ferret, ( M. nigripes ), an endangered species that is highly susceptible to the virus. Siberian polecats were randomized into six treatment groups. Recombinant canine distemper vaccine was administered s.c. at three dose levels (10 4.5 , 10 5.0 , and 10 5.5 plaque-forming units [PFU] per dose) and was administered orally by spraying the vaccine into the oropharnyx at two dose levels (10 5.5 , 10 8.0 PFU per dose). The sixth group of control animals was not vaccinated. For both routes of administration, two 1-ml doses of reconstituted vaccine were delivered 4 wk apart, followed by live virus challenge 3 wk after the second vaccination. During the challenge, Synder Hill test strain CDV obtained from the National Veterinary Services Laboratory in Ames, Iowa, was administered i.p. Serial blood samples for CDV serology were collected immediately before vaccination and challenge, and 10, 15, and 20 days after challenge. Clinical signs and body weights were recorded up to 32 days after challenge. The survival rate in animals receiving vaccine at the highest oral dose (10 8.0 PFU per dose) was 83.3%. Survival rate was 50.0% in the high s.c. and 60.0% in the medium s.c. groups. All animals in the low–s.c. dose, low–oral dose, and control groups died after exposure. Vaccine dose overall (oral and s.c.) and dose in response to s.c. administration when considered alone were significant predictors of survival ( P = 0.006 and P = 0.04, respectively). Among the polecats challenged with virulent virus, those that died became sick sooner than those that survived. Animals that died lost significantly more weight during the 10 days after challenge than did animals that survived ( P = 0.02). Survival rates did not differ by sex, founder female status, or breeding pedigree in any of the treatment groups. Survival rates were higher in animals with increasing serum neutralization titers ( P = 0.027). This study demonstrates the efficacy of oral delivery of a recombinant CDV vaccine in the Siberian polecat. Further studies are needed to evaluate the safety and efficacy of vectored recombinant vaccines in highly susceptible species and especially in those species in which vaccination with modified live CDV has led to disease.

Journal of Zoo and Wildlife Medicine↗
USGS2012

Reversion to virulence and efficacy of an attenuated canarypox vaccine in Hawai'i 'Amakihi ( Hemignathus Virens )

Vaccines may be effective tools for protecting small populations of highly susceptible endangered, captive-reared, or translocated Hawaiian honeycreepers from introduced Avipoxvirus , but their efficacy has not been evaluated. An attenuated Canarypox vaccine that is genetically similar to one of two passerine Avipoxvirus isolates from Hawai&lsquo;i and distinct from Fowlpox was tested to evaluate whether Hawai&lsquo;i &lsquo;Amakihi ( Hemignathus virens ) can be protected from wild isolates of Avipoxvirus from the Hawaiian Islands. Thirty-one (31) Hawai&lsquo;i &lsquo;Amakihi were collected from high-elevation habitats on Mauna Kea Volcano, where pox transmission is rare, and randomly divided into two groups. One group was vaccinated with Poximune C&reg;, whereas the other group received a sham vaccination with sterile water. Four of 15 (27%) vaccinated birds developed life-threatening disseminated lesions or lesions of unusually long duration, whereas one bird never developed a vaccine-associated lesion or &ldquo;take.&rdquo; After vaccine lesions healed, vaccinated birds were randomly divided into three groups of five and challenged with either a wild isolate of Fowlpox (FP) from Hawai&lsquo;i, a Hawai&lsquo;i &lsquo;Amakihi isolate of a Canarypox-like virus (PV1), or a Hawai&lsquo;i &lsquo;Amakihi isolate of a related, but distinct, passerine Avipoxvirus (PV2). Similarly, three random groups of five unvaccinated &lsquo;Amakihi were challenged with the same virus isolates. Vaccinated and unvaccinated &lsquo;Amakihi challenged with FP had transient infections with no clinical signs of infection. Mortality in vaccinated &lsquo;Amakihi challenged with PV1 and PV2 ranged from 0% (0/5) for PV1 to 60% (3/5) for PV2. Mortality in unvaccinated &lsquo;Amakihi ranged from 40% (2/5) for PV1 to 100% (5/5) for PV2. Although the vaccine provided some protection against PV1, both potential for vaccine reversion and low efficacy against PV2 preclude its use in captive or wild honeycreepers.

Hawaii↗
USGS2004

Efficacy of single calfhood vaccination of elk with Brucella abortus strain 19

Brucellosis has been eradicated from cattle in the states of Wyoming, Montana, and Idaho, USA. However, free-ranging elk (Cervus elaphus) that use feedgrounds in the Greater Yellowstone Area (GYA) and bison (Bison bison) in Yellowstone and Grand Teton national parks still have high seroprevalence to the disease and have caused loss of brucellosis-free status in Wyoming. Management tools to control or eliminate the disease are limited; however, wildlife vaccination is among the methods currently used by wildlife managers in Wyoming. We conducted a controlled challenge study of single calfhood vaccination. Elk calves, caught in January and February of 1999 and 2000 and acclimated to captivity for 3 weeks, were randomly assigned to control or vaccinate groups. The vaccinate groups received Brucetta abortus vaccine strain 19 (S19) by hand-delivered intramuscular injection. Calves were raised to adulthood and bred at either 2.5 or 3.5 years of age for 2000 and 1999 captures, respectively. Eighty-nine (44 controls, 45 vaccinates) pregnant elk entered the challenge portion of the study. We challenged elk at mid-gestation with pathogenic B. abortus strain 2308 by intraconjunctival instillation. Abortion occurred in significantly more (P = 0.002) controls (42; 93%) than vaccinates (32; 71%), and vaccine protected 25% of the vaccinate group. We used Brucella culture of fetus/calf tissues to determine the efficacy of vaccination for preventing infection, and we found that the number of infected fetuses/calves did not differ between controls and vaccinates (P = 0.14). Based on these data, single calfhood vaccination with S19 has low efficacy, will likely have only little to moderate effect on Brucella prevalence in elk, and is unlikely to eradicate the disease in wildlife of the GYA.

Journal of Wildlife Management↗
USGS2006

The quest for a safe and effective canine distemper virus vaccine for black-footed ferrets

Canine distemper virus (CDV) causes a systemic disease that is highly virulent to mustelids and other carnivore (Order Carnivora) species and is found worldwide. Endemic canine distemper in wild and domestic carnivores in the United States has made reintroduction of endangered black-footed ferrets (Mustela nigripes) difficult in the absence of safe and effective CDV vaccines and vaccination practices. Toward this end, researchers have explored appropriate animal models and vaccine preparations in highly susceptible species. Published studies involving domestic ferrets (M. putorius furo) using Galaxy-D® and evaluating a recombinant canarypox-vectored vaccine for oral administration are reviewed. In addition, we present new findings in domestic and black-footed ferrets and Siberian polecats (M. eversmannii) that have extended our understanding of CDV in the black-footed ferret and other at-risk carnivore species. Original research presented here includes trials that determined an effective challenge dose (by route) of virulent CDV in domestic ferrets and Siberian polecats; the low likelihood of collateral vaccination with Galaxy-D; the adverse effect of modified-live virus boostering in black-footed ferrets receiving killed vaccine previously and the response of Siberian polecats receiving canarypoxvectored recombinant CDV vaccine (reCDV); the absence of an effect of reCDV vaccination on conception, pregnancy, and neonatal growth in Siberian polecats; and the apparent inefficacy of active reCDV vaccination during the period of passive immunity in young Siberian polecats. In the final section, we discuss emerging concerns and avenues for disease intervention that may present new opportunities to solve problems in vaccine safety, vaccine availability, field vaccine delivery, and other therapeutic modalities.

Conference Paper↗
USGS2024

Vaccination of endangered wildlife as a conservation tool: Hindsights and new horizons in the pandemic era

Vaccines are an established conservation tool that can reduce the threat of infectious disease in endangered wildlife populations. Vaccines exist for many infectious pathogens, and at a time of rapid technological advances in vaccinology, developing vaccines and vaccination programs for free-living endangered wildlife could help efforts to prevent extinctions from disease threats. Vaccination efforts could focus on protecting members of the target species or could be directed at reservoir populations to prevent pathogen spillover. Vaccination strategies need to be substantiated by research on safety and effectiveness, include risk and feasibility assessments, account for differences in host biology and disease epidemiology, and align with relevant regulatory frameworks. Engagement with stakeholders and the public is important to ensure the success of endangered species vaccination programs. Challenges such as funding, regulation, and societal acceptance are barriers to progress in vaccination programs for some species and geographic regions. We recommend the development of scientifically based international guidelines and a transdisciplinary forum with a specific emphasis on endangered wildlife vaccination. New technologies could be used collaboratively to prevent transmission of diseases for which vaccines are not currently available. Careful approaches and enhanced collaborations could help ensure the successful development of wildlife vaccination programs and promote resilience of endangered wildlife populations to increasing anthropogenic and environmental stressors on biodiversity.

Biological Conservation↗
USGS2019

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

Vaccines that autonomously transfer among individuals have been proposed as a strategy to control infectious diseases within inaccessible wildlife populations. However, rates of vaccine spread and epidemiological efficacy in real-world systems remain elusive. Here, we investigate whether topical vaccines that transfer among individuals through social contacts can control vampire bat rabies—a medically and economically important zoonosis in Latin America. Field experiments in three Peruvian bat colonies, which used fluorescent biomarkers as a proxy for the bat-to-bat transfer and ingestion of an oral vaccine, revealed that vaccine transfer would increase population-level immunity up to 2.6 times beyond the same effort using conventional, non-spreadable vaccines. Mathematical models showed that observed levels of vaccine transfer would reduce the probability, size and duration of rabies outbreaks, even at low but realistically achievable levels of vaccine application. Models further predicted that existing vaccines provide substantial advantages over culling bats—the policy currently implemented in North, Central and South America. Linking field studies with biomarkers to mathematical models can inform how spreadable vaccines may combat pathogens of health and conservation concern before costly investments in vaccine design and testing.

Nature Ecology and Evotution↗
USGS2012

Efficacy of a glycoprotein DNA vaccine against viral haemorrhagic septicaemia (VHS) in Pacific herring, Clupea pallasii Valenciennes

Viral haemorrhagic septicaemia virus (VHSV) and its associated disease state, viral haemorrhagic septicaemia (VHS), is hypothesized to be a proximate factor accounting for the decline and failed recovery of Pacific herring populations in Prince William Sound, AK (Marty et al. 1998, 2003, 2010). Survivors of laboratory-induced VHSV epizootics develop resistance to subsequent viral exposure (Kocan et al. 2001; Hershberger et al. 2007, 2010), which is likely the result of immune system recognition of the viral glycoprotein (G) (Lecocq-Xhonneux et al. 1994), a surface antigen that contains neutralizing epitopes (Lorenzen, Olesen & Jorgensen 1990; J&oslash;rgensen et al. 1995) and cell attachment domains (Lecocq-Xhonneux et al. 1994; Estepa & Coll 1996). These properties have proven useful in the development of G-gene-based DNA vaccines for VHSV and a related rhabdovirus, infectious haematopoietic necrosis virus (IHNV) (Anderson et al. 1996; Heppell et al. 1998; Corbeil et al. 1999; Einer-Jensen et al. 2009). Rainbow trout fingerlings, Oncorhynchus mykiss (Walbaum), vaccinated with 1 &micro;g of either the VHS or IHN vaccine are protected from VHS when exposed to virus as early as 4 days (44 degree days) post-vaccination (p.v.) (Lorenzen et al. 2002). At later time points (80 days p.v.; 880 degree days), the level of cross-protection against VHS by IHN vaccination is either completely lost (60 days p.v.; 660 degree days) (3 g rainbow trout; 1 &micro;g vaccine dose) (Lorenzen et al. 2002) or present at intermediate levels (6.5 g rainbow trout; 1 &micro;g vaccine dose) (Einer-Jensen et al. 2009). Comparatively, VHS vaccination remains effective as long as 9 months (2520 degree days) p.v. (100 g rainbow trout; 0.5 &micro;g vaccine dose) (McLauchlan et al. 2003). These results suggest that IHN and VHS vaccination activate a rapid transitory innate immune response against VHSV that is followed by long-term adaptive immunity in VHS-vaccinated trout (Lorenzen et al. 2002).

Journal of Fish Diseases↗
USGS2017

Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine

Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually. In order to develop a new vaccine for potential use in bats, a reservoir of rabies infection for humans and animals alike, an in silico antigen designer tool was used to create a mosaic glycoprotein (MoG) gene using available sequences from the rabies Phylogroup I glycoprotein. This sequence, which represents strains more likely to occur in bats, was cloned into raccoonpox virus (RCN) and the efficacy of this novel RCN-MoG vaccine was compared to RCN-G that expresses the glycoprotein gene from CVS-11 rabies or luciferase (RCN- luc , negative control) in mice and big brown bats ( Eptesicus fuscus ). Mice vaccinated and boosted intradermally with 1 x 10 7 plaque forming units (PFU) of each RCN-rabies vaccine construct developed neutralizing antibodies and survived at significantly higher rates than controls. No significant difference in antibody titers or survival was noted between rabies-vaccinated groups. Bats were vaccinated either oronasally (RCN-G, RCN-MoG) with 5x10 7 PFU or by topical application in glycerin jelly (RCN-MoG, dose 2x10 8 PFU), boosted (same dose and route) at 46 days post vaccination (dpv), and then challenged with wild-type big brown variant RABV at 65 dpv. Prior to challenge, 90% of RCN-G and 75% of RCN-MoG oronasally vaccinated bats had detectable levels of serum rabies neutralizing antibodies. Bats from the RCN- luc and topically vaccinated RCN-MoG groups did not have measurable antibody responses. The RCN-rabies constructs were highly protective and not significantly different from each other. RCN-MoG provided 100% protection (n = 9) when delivered oronasally and 83% protection (n = 6) when delivered topically; protection provided by the RCN-G construct was 70% (n = 10). All rabies-vaccinated bats survived at a significantly (P ≤ 0.02) higher rate than control bats (12%; n = 8). We have demonstrated the efficacy of a novel, in silico designed rabies MoG antigen that conferred protection from rabies challenge in mice and big brown bats in laboratory studies. With further development, topical or oronasal administration of the RCN-MoG vaccine could potentially mitigate rabies in wild bat populations, reducing spillover of this deadly disease into humans, domestic mammals, and other wildlife.

PLoS Neglected Tropical Diseases↗