A new animal vaccination strategy has been proposed to address the epidemiology issue of the zoonotic spillover. Pathobiologists are now looking at the possibility of transmissible vaccinations that spread across individuals like their target pathogens.
Many of these illnesses have the potential to spread to humans, or have already done so. SARS-CoV-2, the virus that causes COVID-19, is only one of the most recent diseases caused by zoonotic spillover. Infectious disease experts are aware of many animal populations that may be used as reservoirs for zoonotic viruses. Vaccination of individual animals is only one of the many methods used to slow the spread of these diseases.
Vaccinate animals to prevent disease spread
SARS, MERS, Ebola, Nipah, and a range of arenavirus infections spread across human populations, often due to poor transmission in humans, coupled with intense public health surveillance efforts in the early stages of an emerging epidemic. According to Nuismer, researchers at the University of Idaho, nuismer, Bull, and their research groups have done extensive monitoring of viral and vaccine transmission.
Unlike conventional vaccines, avoiding these diseases before they can be spread to humans would result in significant reductions in death and economic costs of epidemics. Currently, two main methods to control zoonotic pathogens before they can spread illness to humans include: culling diseased animal populations and vaccinating vulnerable animal populations by catch and release programs, or distributing vaccine-laced baits. Both methods have their disadvantages, particularly if animals are in difficult-to-reach locations. Transmissible vaccinations
There are two methods to spread vaccinations from one animal to another:
Are developed from live viruses, injected into the animal, and they may be passed to indefinite numbers of other animals.
Transferable vaccinations, like vaccine-laced baits, are not contagious and will not spread as much as strongly transmissible vaccinations.
Attenuated or recombinant vaccines
Virologists are looking at two kinds of vaccinations as potential candidates for transmissible vaccine programs: attenuated and recombinant vector vaccines.2
Live attenuated vaccines are made from a weakened version of the pathogenic virus, which can replicate without causing illness. Genetic manipulation has reduced viral growth rate. However, as Nuismer and Bull point out, virulence and transmissibility are generally linked. This means that attenuated vaccinations that are too weak to cause disease may also be unable to transmit to other hosts.
Recombinant vector vaccinations employ a benign virus, into which parts of the pathogens genome have been inserted. Many factors, including their own transmission rate and whether the vector is already present in the target species, may be hemothy. Immunity to the transgenic inserts must be immunogenic, but also adequate to survive self-replication.
An emerging technology
Transferable vaccines have characteristics that are similar to those seen in current vaccination applications with vaccine-laced baits, and therefore are well-known.
Transmissible vaccinations are another emerging method that requires further risk assessment. One such risk is that increased replication allows for evolution of attenuated vaccines back to virulence. This is because the vaccine must self-replicate to spread. These viruses may be best used in conjunction with mutations or nucleotide modifications in their genetic code.
Because evolutionary mutations are likely to cause the vaccine to revert back to the original benign virus, this means it is also likely to lose the ability to function as a vaccine. Increasing the number of pathogen antigens inserted into the vectors genome may help prolong the duration of the vaccine.
Nuismer and Bull argue that recombinant vaccines are a priori the most promising approach for a transmissible vaccine. However, if a recombinant vaccine utilizes a novel technique to avoid immunity already present in a population, there is still a possibility of evolution into a pathogen.
Professor Jorge Osorio has agreed that recombinant vaccinations are safer than attenuated vaccinations. He has an experience in vaccine development for many different emerging diseases. He prefers to work with transferable vaccines because of the risks associated with the transmission of viruses. There is a possibility that viruses used to create these vaccinations may spread to individuals or species outside the target population, including to humans.
Nuismer and Bull discuss possible solutions to mitigate these threats, including the use of recombinant vector vaccines. This approach might include self-regulatory mechanisms that keep transmission low enough that the virus would eventually self-extinguish. Tests of species-specific vaccinations would be conducted in related reservoir species, to determine the likelihood of cross-species spillover and effectiveness.
Promising computational models
In 2001, a successful study of a recombinant vaccine for rabbit hemorrhagic disease in an isolated population of wild rabbits was reported in the journal Vaccine.4 Half of the rabbit population was injected with the vaccine before publication; one month later, half of the uninoculated population was found to be vaccinated through transmission of the vaccine. In 1994, similar methods were proposed to sterilize feral mammal populations in Australia.5
Despite these early testing, effective transmissible vaccines are still largely theoretical. Most research on this topic are computational, indicating that transmissible vaccines will be effective in laboratory and field trials. These results demonstrate that mathematical models will have to be reviewed in laboratory and field trials. Despite these findings, these limitations may be made about vector transmissibility and vaccine infection only if they are tested in vivo. Ideal vaccine vectors will need to infect hosts if there is an existing infection or immunity.
When addressing well-known zoonotic pathogens, such as rabies, the initial development of transmissible vaccines would be effective. As Nuismer and Bull argue, rabies is a good target to start with, because it already has a wildlife vaccination that only needs to be self-disseminated. To effectively eradicate rabies through this method, a different vaccination would be required to target each reservoir species.
The Osorio group is working on the development of a transferable rabies vaccination which would be applied to bats in a jelly-like substance. The group suggested this technique on white-nose syndrome and tested the theory using fluorescent biomarkersthat same year.6,7 The methods and results of the rabies vaccination test will be described in an upcoming paper, according to Osorio.
Human application is unlikely
Osorio claims that some live human vaccinations have already demonstrated transposibility. This can happen with inoculations that result in attenuated viruses being present in mucosal membranes, such as a nasal spray flu vaccine. However, he cautions that communication is still too costly to be desirable in a wildlife vaccine. Involvements such as the polio vaccine reintroduce careful risk assessment.
Vaccine researchers believe that transmitsible vaccines, at least in initial use, should be targeted towards animal populations. However, it is difficult to verify high-risk pathogens before they are discovered, even with wildlife surveillance and virus characterization. Decomposable vaccines will be most effective if it comes to previous research on well-known zoonotic viruses.
Biological information about the reservoir species will assist scientists in determining which animal is likely to spread the vaccine the farthest. Vaccine developers will also need to select between transmissible and transferable vaccines, and design their vector for minimal risk and maximum effectiveness.
A recent study by Nuismers study demonstrates the potential to utilize betaherpesviruses as vectors for recombinant vaccines.8 These viruses are beneficial candidates for vaccine vectors due to their large taxonomic distribution across large groups of reservoir species, increased species specificity, and mild or undetectable virulence in most natural reservoirs.
For successful transmissible vaccines, extensive research will be required. According to Nuismer and Bull, the effectiveness of recombinant transmissible vaccines will likely be evaluated at an all-time low.
1.Nuismer SL and Bull JJ. Self-disseminating vaccinations to combat zoonoses. Nat Ecol Evol. 2020;4(9):1168-1173. doi: 10.1038/s41559-020-1254-y
2.Layman NC, Tuschhoff BM, and Nuismer SL. Developing transmissible viral vaccines for evolutionary robustness and maximum efficiency. Virus Evolution. 2021;7(1). doi: 10.1093/ve/veab002.
3.Famulare M, Chang S, Iber J, and others. Sabin vaccine reversion in the field: a comprehensive analysis of sabin-Like poliovirus isolates in Nigeria. Sandri-Goldin RM, ed. Journal of Virology. 2016;90(1):317-331. doi: 10.1128/jvi.01532-15.
1.Torres JM, Sanchez C, Ramrez MA, and others in a field study of a transmissible recombinant vaccine against myxomatosis and rabbit hemorrhagic disease. Vaccine. 2001;19(31):4536-4543. doi: 10.1016/s0264-410x(01)00184-0
C. Virus-vectored immunocontraception of feral mammals. Reprod Fertil Dev. 1994;6(3):281. doi: 10.1071/rd9940281.
6.Rocke TE, Kingstad-Bakke B, Wuthrich M, and others. Virally-vectored vaccination candidates against white-nose syndrome induce anti-fungal immune responses in young brown bats (Myotis lucifugus). Sci Rep. 2019;9(1). doi: 10.1038/s41598-019-43210-w.
7.Bakker KM, Rocke TE, and Osorio JE, et al. Fluorescent biomarkers demonstrate potential for spreadable vaccinations to control disease transmission in wild bats. Nat Ecol Evol. 2019;3(12):1697-1704. doi: 10.1038/s41559-019-1032-x.
8. Varrelman TJ, Remien CH, Basinski AJ, Gorman S, Redwood A, and Nuismer SL. PNAS. 2022;119(4):e2108610119. doi: 10.1073/pnas.2108610119.