In the two years since the first reported case of the SARS-CoV-2 virus, a dedicated coalition of global research has been investigating whether it is a so-called ‘zoonotic virus’ — that is, whether the virus first arose in an animal before it was transmitted to a human. Zoonotic viruses are very well-documented phenomena, and the evidence for SARS-CoV-2 being one is quite strong.
But even if the virus that caused the COVID-19 pandemic is not zoonotic, researchers believe that some populations of wild animals that frequently come into contact with humans carry many other zoonotic viruses. These viruses could easily be the seeds of future pandemics if we don’t take precautionary measures against them.
We cannot necessarily rely on vaccines to steer us through future pandemics. After all, although close to 60 per cent of the world population has received at least one dose of a COVID-19 vaccine, only 9.5 per cent of people living in low-income countries have received their first dose. Vaccine inequity is among the many reasons that COVID-19 is still rampant today. So what else can we do to prevent or mitigate the impact of future pandemics?
A recent review published in Nature examined the idea of using self-disseminating vaccines to target wildlife before pathogens are transmitted to humans and create widespread infections. While the potential benefits of this type of vaccine can be immense, another paper published in a later issue of the same journal notes that there are still many safety concerns that need to be addressed. This begs the question: how would these vaccines work, and what are those potential safety concerns?
Basics of self-disseminating vaccines
Self-disseminating vaccines rely on animals that are directly vaccinated through injection to spread ‘vaccine infections’ through their interactions among wildlife populations. The effectiveness of these vaccines is quantified by the rate at which they spread — their ‘reproduction rate’ — which is denoted by the index R0. This index represents the number of vaccine infections caused by directly vaccinated individuals. So, if a vaccine has an R0 of two, then every vaccinated animal will spread the vaccine to two other animals.
Overall, there are two mechanisms in which the self-disseminating vaccines could spread — namely, ‘transmissible’ and ‘transferable’ vaccines. Transmissible vaccines are adept at spreading through infection after the first animals have been directly injected. If their reproductivity exceeds that of a target pathogen, transmissible vaccines can eliminate the pathogen from a population altogether. This model works in scenarios in which inoculated individuals are introduced to the entirety of the population that is susceptible to the targeted pathogen.
For transmissible vaccines with greater safety concerns, vaccines with an R0 of less than one — that is, vaccines that spread slowly among the population — would be ideal for eradicating the target pathogen from a wild population. This safety measure ensures that the transmissible vaccine would be eliminated from the population as well, once continuous introduction of the vaccine halts. This is to avoid out-of-control evolution of the vaccine itself.
There is also another, less efficient, method for vaccine self-dissemination. Vaccines that use this method are generally known as ‘transferable vaccines.’ Unlike their transmissible counterparts, transferable vaccines can only be transferred from each inoculated individual to one other member of its species.
Due to their single-use nature, transferable vaccines are not as efficient as transmissible vaccines. While their limitations might present some challenges, some scientists argue that this type is preferable because of the safety concerns of transmissible vaccines.
Strategies for implementing self-disseminating vaccines
Transmissible and transferable vaccines provide the means for additional animals to be vaccinated for ‘free’ by animals that were vaccinated by traditional injection. Self-disseminating vaccines must undergo careful considerations and the populations they target must be evaluated before the vaccines are implemented.
Transferable vaccines would not be able to achieve satisfactory results if their designers do not have a thorough understanding of the basic biology of the targeted animals. Since an infectious host is required to spread immunity, the ways in which members of the target species interact could have significant implications in the efficacy of self-transmissible vaccines. One important example of this is bat colonies, since some bat species carry several potential zoonotic viruses. The act of grooming enables bats to orally deliver vaccines to between 1.45 and 2.11 other members of their colony.
For transmissible vaccines, additional planning for the logistics of administering the vaccine to a large population is necessary. Scientists must first select individuals to directly vaccinate out of a wild population or community. This selection must be carried out efficiently to ensure an effective rate of immunization and to optimize the spread of the vaccine. Even when all the conditions of self-disseminating vaccines are met, they still need to be administered to the right animals so they can be passed on effectively.
Vaccine inner workings
Transmissible vaccines, by nature, require some way to spread immunity among the target population. One approach to vaccine development is to insert a gene from a targeted pathogen into a harmless agent that will pass on the virus, called a viral vector. These stitched-together viral packages are also called recombinant viruses.
Once inside a host, the vaccine prompts an immune response, which confers protection from the target pathogen. If scientists are able to access a viral vector that can spread faster than the target pathogen, then using that to make a recombinant vaccine might be most effective for the situation.
Once a transmissible vaccine is introduced to a reservoir, the unavoidable evolution of the viruses or viral vectors in the wild becomes a cause for concern. There is even a possibility for a modified virus to revert back to its former pathogenic state. Attenuated vaccines — copies of the virus that cannot reproduce — are unlikely to be suited for eliminating human pathogens, because they only reduce viruses’ growth rate instead of shutting down all forms of viral growth completely.
That being said, researchers predict that when recombinant vectors evolve, it will most likely result in the vectors being restored to their initial and harmless state. No matter what their predictions are, though, the replication and spread of transmissible vaccines must be closely monitored to minimize undesired and dangerous evolution.
Transmissible vaccines can be more efficient than transferable vaccines, and therefore might logically seem like the more preferable option for self-disseminating vaccines. However, a group of experts who published a correspondence paper in Nature think otherwise. They argue that self-transferable vaccines are the safer approach to carry out mass vaccination campaigns. Since no one can definitively predict the outcome of the evolution of transmissible vaccines in the wild, there is no way of fully knowing the risks associated with introducing transmissible vaccines to reservoirs. Transmissible vaccines may defeat their own purpose of controlling the spread of pathogens by evolving into pathogens themselves.
As researchers manipulate viral vectors in the search and development of self-disseminating vaccines, their insights could also be used to create dangerous bioweapons. Research that emphasizes optimizing transmissibility and genomic stability of viral vectors may be redirected to developing potential artificially-produced pandemic agents. Due to all of these safety and security concerns, the authors of this correspondence recommended implementing transferable vaccines over transmissible vaccines.
Regardless of the type of self-disseminating vaccine, their potential evolution must be carefully modelled to gain insight into their benefits for wild populations of animals. Self-disseminating vaccines may be in their early days of development, but they still offer a novel approach for humans to combat emerging infectious diseases.