Bounties attract serious brainpower to the challenge.
Viruses and other pathogens transmit all the time, causing diseases and pandemics. What if we could hijack their systems to turn viruses into vaccines that transmit?
Though vaccines are the best armours against infection and they have been proven to protect hosts, the full potential of vaccination is far from realized. In cases of rapidly transmitting infections, it is even more important to vaccinate the population at a rate that is faster than the actual disease transmission if we are to attain herd immunity. However, this seems to be very challenging when logistical, social and other reasons are factored in.
For (re)emerging pathogens that can spill to humans from wildlife, the application of preventive vaccines to curtail the potential emergence is still an idea confined in theory.
To proactively tackle the issue of spillover and zoonoses from wildlife, and to reach herd immunity in the human population at a faster rate, a new approach to vaccination is being heavily pursued, at least in experimental field trials. A study very recently published in PLOS Biology describes a systematic approach to using a ‘transmissible’ (or self-disseminating) vaccine. In their study, the scientists used Desmodus rotundus betaherpesvirus (DrBHV) as a vector for a vaccine strain of bat-transmitted rabies; resulting in a vaccine strain that the bats pass among each other with natural benign infections. Earlier, another group had reported the development of a transmissible vaccine against myxomatosis and rabbit hemorrhagic disease (RHD) based on a recombinant myxoma virus that contained RHDV capsid protein. In this field trial, the recombinant transmissible virus was able to protect at least 50% of the rabbit population without any undesirable consequences .
How do these transmissible vaccines work?
First, an ideal vector is identified. This ideal vector is any virus that circulates naturally among the target population without causing any disease (there are many such viruses). Next, the viral vector genome is edited using genetic engineering to incorporate a portion of the pathogen that is recognized by the immune system of the animal reservoir. This process endows the vector virus with the capacity to induce immunity to the pathogen in question. When the pathogen gene is optimally carried by the vector, the resulting vaccine will efficiently transmit among the animals and offer natural immunization as it transmits. In principle, this is elegant and straightforward.
Current issues and challenges:
The intrinsic high mutational frequency of viruses makes it harder to maintain the homogeneity of the viral vector over time.
The evolutionary loss of transgene function is another issue: with each replication in the animal host, the vaccine can gradually lose its capacity to induce effective immunity.
However, given our current understanding of viruses, immunology and epidemiology, this is an attainable feat. Once developed, the vaccine candidates can be tried in captive animals and then gradually upscaled to semi-natural to natural environments for controlling zoonoses.
How do you think we can create the best vaccines that transmit on their own? Can you think of other alternative ways?
Superinfection could be a useful feature when choosing a vector for transmissible vaccine
Subash ChapagainApr 22, 2022
Superinfection is the biological process when a cell/organism previously infected by one virus gets co-infected with a different strain of the same virus later on. This feature can be extremely useful if we are to design vaccines that transmit, to address the issue raised by Michaela D in the contribution above.
Generally, cells/organisms would develop immunity against a pathogen upon their first encounter and develop a lasting immunological memory that will fight off the pathogen later on with the antibodies produced using that memory. Though in normal conditions this is a highly desirable default biological process, for virus vaccines this might be a downside because if we have to introduce a new vaccine variant to counter the temporal inefficiency of vaccine resulting from mutations (which is expected). However, if we can find a viral vector that is capable of infecting AGAIN the cells that the original variant of the vector infected in the past, the new vaccine would work as effectively as the old one.
In fact, this is exactly what the researchers found in this study. Using genomic sequencing to determine the overall patterns , they found that DrBHV can infect bats previously infected by other strains of DrBHV and that preexisting immunity may not hinder the transmissible vaccine if DrBHV vector is used. This finding is very exciting and sets a new roadmap to develop such self-disseminating vaccines.
Please leave the feedback on this idea
Vaccine viruses with a "deactivation trigger" that is pulled when they are not effective anymore
Michaela DApr 21, 2022
As you mentioned, the more a virus replicates the more mutations it accumulates. As a result, the transgene (the vaccine part) will also accumulate mutations and at some point, it may change too much to induce immunity anymore. A solution would be to reintroduce in the population the virus with the original transgene. However, the new virus-vaccine will have to compete with the older, mutated, one. I assume that for people that have been infected with old virus-vaccine (which is not effective anymore) will be harder to gain vaccine immunity from the new virus-vaccine? That is because their immune system will remember the virus and fight it before it gets the chance to integrate in the cells.
A solution to that would be to introduce in the virus-vaccine a "deactivation trigger" that is pulled when they reach a certain number of mutations. This number would be the number of mutations that would render the vaccine not relevant anymore.
How would we do that?
We would design the viral genetic material in a way that it can only tolerate a specific number of mutations. Once this number of mutations is reached the virus would not be able to replicate anymore. To get more technical: The ideal genetic part to focus is the part responsible for viral replication. For the genetic design: design the genetic sequence in such a way that is functinal for now but certain number of detrimental mutations will occur in a calculated time in the future.
As a result, the time the vaccine loses its effectiveness will coincide with the time the virus stops replicating. So, when we reintroduce the original, effective virus, it will not have to compete with the old one.
Please leave the feedback on this idea
Herpes simplex virus as a self-transmissible vaccine?
J. NikolaApr 27, 2022
I had a similar idea with herpes viruses in this session.
They are highly transmissible and stay usually forever in human nerve cells. If the symptoms were reduced and proteins of our choice introduced by genetic engineering, they could potentially be used as self-transmissible vaccines that reactivate when the immunity (or, preferably, the antibody concentration) drops below normal rates.
What do you think? Do these two sessions share something else?
Please leave the feedback on this idea
Create a chimeric peptide between a mosquito saliva protein and some viral capsid/envelope protein
mschiav3May 06, 2022
Very unusual idea, and very unfeasible considering biosafety, however, it will spread in nature very quicklly and you will have a reinforcement of the immune response every bite you get.
It may help to reach very isolated communities and it can be used in a gene drive system.
Not hard to develop but practically impossible to pass through regulation considering ethical and biosafety issues.
And it will not be transmissible by person 2 person but by mosquito 2 person.