A new animal vaccination strategy has been proposed to address the epidemiological issue of zoonotic spillover. Pathobiological scientists are exploring the possibility of transmitsible vaccinations that spread through human beings similar to their target pathogens.
Many of these diseases 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 approaches used to mitigate these spreads.
Vaccinate animals to prevent disease spread
SARS, MERS, Ebola, Nipah, and an array of arenavirus infections are common in humans, but they are often eliminated only as a result of poor human transmission, according to Scott Nuismer and James Bull, the researchers at the University of Idaho. Nuismer, Bull and their research groups have completed extensive modelling of viral and vaccine transmission.
Often times, reducing the amount of effort required to vaccinate animals is a result of stopping these diseases before they can spread to humans. Currently, two main methods to combat zoonotic pathogens are removing livestock populations, such as culling catch and release programs. Both methods have their limitations, especially when the animal populations in question have rapid turnover or are in difficult-to-reach locations. Transmissible vaccines will significantly reduce the amount of effort required to vaccinate animals.
Impfstoffe are mutated from one animal to another by two methods:
Are developed from live viruses, injected into the animal, and can be passed to indefinite amounts of other animals.
Transferable vaccines, like vaccine-laced baits, are not contagious and will not spread as much as strongly transmissible vaccines.
Attenuated or recombinant vaccines
Virologists are considering two types of vaccinations as potential candidates for transmissible vaccination programs: attenuated and recombinant vector vaccines.2
Live attenuated vaccines are made from a weakened version of the pathogenic virus, which can then replicate without causing disease. Viral growth rate is reduced by genetic manipulation. However, as Nuismer and Bull argue, attenuated vaccines that are too weak to cause illness may also be unable to transmit to other hosts.
The recombinant vector vaccines use a benign virus, into which pieces of the pathogens genome have been inserted. Many factors influence the choice of the benign vector, which may include its own transmission rate and whether it is already present in the target species. Immunity to either the vector or the pathogen will slow the spread of the vaccine. Transgenic inserts must also be stable enough to survive through self-replication.
An emerging technology
Transferable vaccinations have characteristics that are similar to those seen today with vaccine-laced baits, and are therefore well understood.
Transmissible vaccines are an emerging technology that requires further risk analysis. One such risk is that increased replication has permisted that the vaccine must self-replicate to spread. These viruses may be best used in patients who have low poliovirus immunity, according to Nuismer and Bull.
Because of its evolutionary mutations, the vaccine is likely to lose its potential to function as a vaccine. This is because increasing the number of pathogen antigens inserted into the vectors genome may improve the life of the vaccine.
Nuismer and Bull argue that recombinant vaccines are a priori the most promising strategy for a transmissible vaccine. However, they argue that if a recombinant vaccine uses a novel technique to avoid immunity already present in a population, there is still a danger of evolution into a pathogen.
Prof. Jorge Osorio has agreed that recombinant vaccinations are more effective than attenuated vaccinations. He has worked in vaccine development for many different emerging diseases. He is preferable to work with transferable vaccines because of the risks associated with transmission viruses. There is a possibility that the viruses used to create these vaccinations may spread to individuals or species outside the target population, including humans.
In addition to using recombinant vector vaccinations, Nuismer and Bull discuss their potential strategies. The use of species-specific vectors might reduce the possibility that these viruses might spread outside the target population. Vaccine design might include self-regulatory mechanisms that prevent transmission from spreading to the outside, resulting in a cross-species spillover.
Promising computational models
In 2001, a successful investigation of a recombinant vaccination 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 vaccination before being released. One month later, half of the uninoculated population was discovered to be vaccinated through transmission of the vaccination. In 1994, similar methods were suggested to sterilize feral mammal populations in Australia.
Although these early tests suggest effective transmissible vaccinations are still largely theoretical. Most research on this topic is computational, implying that transmissible vaccinations can be effective in zoonotic disease control. Mathematical models have limitations that will need to be examined in laboratory and field tests. These models make several assumptions about vector transmissibility and vaccine infection that can only be tested in vivo. Ideal vaccine vectors will need to infect hosts despite the potential presence of an existing infection or immunity.
When it comes to identifying well-known zoonotic pathogens, such as rabies, the initial development of transmissible vaccines would be beneficial. As Nuismer and Bull argue, rabies is a good starting point because it already has a wildlife vaccine that only needs to be self-disseminated. However, to effectively eliminate rabies through this method, it may require a different vaccine to target each reservoir species.
The Osorios team is working on developing a transferable rabies vaccination that would be applied to bats in a jelly-like substance. In a future paper, the group suggested a technique on white-nose syndrome and tested the theory with fluorescent biomarkers.6,7 The methods and results of the rabies vaccination test will be described.
Human application is unlikely
Osorio believes that some live human vaccines have some transmissibility. This can happen in inoculations that result in attenuated viruses being present in mucosal membranes, such as a nasal spray flu vaccine. However, he believes that there are still too many hazards involved in transmitsibility for it to be a desirable quality in a wildlife vaccine. Involvements such as the polio vaccine reverting to wild-type virulence require careful risk assessment.
Although this is difficult to do reliably with wildlife surveillance and virus characterization, vaccines will be most effective if compared to previous studies on well-known zoonotic viruses.
Vaccine developers will also need to determine the best vaccination timing and which individuals will likely to spread the vaccine the farthest. Layman, Tuschhoff, and Nuismer argue that the durability of weakly transmissible vaccinations is limited by competition with the pathogen, but that of highly transmissible vaccinations is limited by evolutionary stability.
A recent study by Nuismers reveals that vector choice is vital. Ideal vectors will have large, tolerant genomes, low mutation rates, and are not unfettered by trade-offs between important epidemiological and evolutionary parameters.8 These viruses are well candidates for vaccine vectors due to their extensive taxonomic distribution across important groups of reservoir species, high species specificity, and mild or undetectable virulence in most natural reservoirs.
Extensive research will be necessary to achieve successful transmissible vaccinations. According to Nuismer and Bull, the successful application of recombinant transsible vaccines will likely require at least the consideration of efficacy, transmission rates, antigenic redundancy, and mutation rates.
References:
1.Nuismer SL and Bull JJ. Self-disseminating vaccines to suppress 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 vaccinations for evolutionary robustness and maximum efficiency. Virus Evolution. 2021;7(1). doi: 10.1093/ve/veab002.
Physik B, Amir A, Wildh, and Jossa Mauricio A, both published in The Guardian, 1995.
1.Tribes JM, Sanchez C, Ramrez MA, and coll. first 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.
5. Tyndale-Biscoe 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 response in little brown bats (Myotis lucifugus) Rev. Sci. 2019;9(1). doi:10.138/s41598-019-43210-w.
7.Bakker KM, Rocke TE, Osorio JE, and others. Biomarkers from fluorescence suggest opportunities for spreadable vaccinations to prevent 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.
