Possibility of a Transmissible Rabies Vaccine

Based On: Bakker, KM., Rocke, TE., Osorio, JE., Abbott, RC., … Streicker, DG. (2019) Fluorescent biomarkers demonstrate prospects for spreadable vaccines to control disease transmission in wild bats. Nature Ecology and Evolution, 3, 1697-1704.

            Many diseases that afflict humans, especially viral diseases, are transmitted into human populations from bats. In a recent study in Peru, researchers captured small portions of vampire bat colonies and applied orotopical gels to their fur in order to determine the ability of certain substances to be passed between bats.¹ An orotopical gel is a substance that can be placed on the fur of the bat and will be transferred into other bats and the systems of the bat itself through oral contact and grooming. This study investigated the rates of orotopical transfer in order to computationally model how a potential rabies vaccine would spread through bat colonies in order to decrease the prevalence of the virus in bat populations. Vaccines are substances that are given to animals and humans in order to elicit an immune response that protects the organism from being pathologically infected by a certain virus or bacteria. Vaccines are the most effective way in decreasing the transmission of disease and they help protect the lives of animals and humans alike. Bakker et al. found that the application of orotopical gels to captured bats from colonies can possibly increase the rate of rabies vaccination and reduce the overall rates of the virus.

            This study was conducted because vampire bats are a common reservoir host of rabies. Rabies is a small RNA virus that can infect a wide range of mammals, including bats, rodents, canines, and humans.² The disease infects many different cell types, including neurons of the central nervous system, causing inflammation in the brain and spinal cord that can lead to paralysis and death. Many animals will exhibit altered aggressive behavior prior to death which increases transmission of the virus through saliva entering broken skin of other organisms due to bites and scratches.³ The study was conducted with the hope to decrease the overall transmission of rabies to livestock, domestic animals, and humans by reducing the prevalence of rabies in the bat reservoir, or the animal that the virus persists in without causing symptoms.

First, the researchers wanted to determine what percentage of the bat colony would be exposed to their orotopoical gel biomarker, rhodamine B (RB), when it was applied to a certain proportion of the colony. RB causes hair follicles to fluoresce after ingestion, so was an ideal biomarker to track which individuals were attaining the substance in measurable quantities. It was found that in two different colonies, there was over 84% and 92% ingestion of RB in bats after application or transfer of the substance. This data suggests that each bat that had RB applied to their fur transferred the gel to an average of 1.45-2.11 untreated individuals depending on the colony. This would be equivalent to a 2.6 fold increase in population-level coverage. To further evaluate mechanisms of transfer, the group applied differently colored ultraviolet powder to furs of young and adult male and female bats. This allowed them to track which demographics were interacting with each other and if there would be an advantage of applying orotopical vaccines to a particular subset of the colony. They found that adult male bats had the greatest amount of contact with both sexes and should thus be targets as the recipients of the orotopical vaccine.

Figure 1: Number of individuals vaccinated in different colonies following initial application of vaccine to a smaller proportion demonstrates increased rates. (a) shows the vaccinated individuals in the LMA5 colony, (b) shows the vaccinated individuals in the LMA6 colony, and (c) shows the vaccinated individuals in the LMA12 colony which migrated during data collection and is therefore excluded from this review. 

          After the initial collection of data from the smaller colonies, the research team performed computational models of how the rabies vaccines would alter the population susceptibility to infection and the prevalence of rabies within it. They found that if 20% of the colony were to have the vaccine applied, this would lead to an approximately 40% overall vaccination rate in the colony. Depending on the actual R₀ of rabies, or the number of cases that would result from a single infected individual, the outbreak size would decrease by 45-75%. The researchers modeled their results for multiple values of R₀ because estimates for this basic reproduction number range from as little as 0.6-2.0. Interestingly, the outbreak reduction was not found to be linear to the percentage of the population that initially had vaccine applied. It was found that after 30% of the population was vaccinated, with every 5% increase in vaccinations, there was a less than 5% reduction of outbreak size. This data will be useful for future vaccinations so the greatest rabies reduction can occur at the lowest overall cost.

Figure 2: Outbreak size and duration was decreased with increasing levels of vaccination in bat populations through transmissible vaccines. (a) demonstrates that with different percentages of applied vaccine, outbreak size will decrease to a certain extent depending on basic reproduction number, (b) demonstrates the percentage protected based upon vaccination rates, (c) demonstrates the percent reduction in outbreak size after vaccine application, and (d) demonstrates the decreasing additional reduction after 30% have vaccine initially applied. 

Finally, the research team was interested in determining whether or not the transmissible vaccine would be more effective at reducing the chance of a rabies outbreak in bat colonies as compared with already existing measures that reduce risk. Currently, rabies outbreak reduction occurs through the application of “vampiricide,” a topical poison that results in the death of infected and infectable bats via oral ingestion. Not only is vampiricide controversial for ethical reasons, but it can also affect local ecosystems as well as possibly lead to the transmission of infections from one colony to another as bats seek other suitable mates due to declining numbers within their own colony. It was found that in preventative (application to prevent rabies invasion into historically uninfected population) and proactive (application in an area with low levels of rabies, but not in the colony itself) scenarios, vaccination was greatly favored over culling in order to reduce outbreak size and duration. In order for culling to be favored, 60% or more of the population would have to have vampiricide directly applied, which is an impractical proportion of the colony to capture and treat. Even in reactionary cases (application 60 days after a single rabies infection), vaccination was favored if less than 20% of the population could be captured and treated, which is a realistically attainable proportion.

Figure 3: Transmissible vaccination was preferred over vampiricide in preventative, proactive, and reactionary scenarios. (a-c) demonstrate that vaccination reduces outbreak size and duration in preventative scenarios, (d-f) demonstrate that vaccination reduces outbreak size and duration in proactive scenarios, and (g,h) demonstrate that vaccination is favored for low percentages, but not high, in reactionary scenario.

This study is extremely important for the future of infections that are present in bats as a reservoir host. While this study specifically analyzed the reduction of rabies outbreaks in vampire bats in Peru, the same principle of transmissible vaccines may be applicable to other infections as well. Bakker et al. showed that transmissible vaccines would be effective at reducing the risk of rabies outbreaks in vampire bats, thereby reducing the risk that infections would be transmitted to livestock, domestic animals, and humans. Transmissible vaccines would allow for a greater percentage of wild-life populations to be vaccinated than can physically be captured and treated by humans. Transmissible vaccination also offers an alternative to culling methods, which are not a sustainable long-term solution ethically, ecologically, or economically for rabies reduction. One barrier that must be overcome is the current cost of large scale production of rabies vaccines, one reason that biomarkers were used rather than the vaccine in this initial study. As vaccine development improves, this method of transmissible vaccination for rabies, and other viruses carried by bats, will become favored to reduce the possibility of outbreaks. Until that time, orotopical vaccination should be used in combination with vampiricide in order to reduce the likelihood of a rabies outbreak in bat colonies that could have detrimental effects on humans.

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Bakker, KM., Rocke, TE., Osorio, JE., Abbott, RC., … Streicker, DG. (2019) Fluorescent biomarkers demonstrate prospects for spreadable vaccines to control disease transmission in wild bats. Nature Ecology and Evolution, 3, 1697-1704. 

Fooks, AR., Cliquet, F., Finke, S., Freuling, C., Hemachudha, T., … Banyard, AC. (2017). Rabies. Nature Reviews, 3(17091), 1-19. 

World Health Organization. (2019). “Rabies.” Health Topics.