Designer viruses as vaccines: yea or nay?

[hutchphd]

To me it seems that the response to COVID19 was limited more by social reluctance to vaccinate (and foot the bill for said pan-vaccination) than the medical prowess necessary for the developmaent of safe and effective vaccines. For a hypothetical more deadly virus this could have catastrophic ramifications. The appearance of the OMICRON variant appears to be more effective at (finally?) limiting the pandemic than the previous vaccinations.
This immediately suggests using a designer virus in lieu of a vaccine. Is this just a foolishly risky idea? How close are we to being scientifically able to do it? Of course there are a host of issues.

 

[TeethWhitener]

What’s the difference between your idea and the adenoviral vector used in (e.g.,) the J&J COVID vax?

 

[TeethWhitener]

Wait a sec, do you mean releasing a replication-competent weakened virus onto an unsuspecting population? I hope everyone sees the ethical issues with this.

 

[hutchphd]

Yes that is what I wanted to discuss. If the alternative is billions of dead people, what should the ethics look like? I truly don't know.

 

[TeethWhitener]

1. Dosing people with experimental medication without their knowledge or consent is unethical (for many many reasons).
2. Especially in this case, if a virus can replicate, it can evolve…in an uncontrolled manner…into something really really bad.

This is less of a biology question and more of an ethics question. Maybe it belongs in general discussion instead of in the biology forum.

 

[hutchphd]

Yes that is what I wanted to discuss. If the alternative is billions of dead people, what should the ethics look like? I truly don't know.

This is less of a biology question and more of an ethics question. Maybe it belongs in general discussion instead of in the biology forum.

I am fine with either, but I also hoped to provoke some technical discussion as to the level of control we have with the technology. Can we produce designer viruses? How direct is the result?

 

[TeethWhitener]

If the alternative is billions of dead people, what should the ethics look like? I truly don't know.

Is the alternative billions of dead people? If COVID had a 20% fatality rate instead of a 2% fatality rate, I have to imagine that would impact vaccine hesitancy. Add to that the fact that right now, the main reason billions of people haven't been vaccinated is because they haven't been given the opportunity.

Can we produce designer viruses? How direct is the result?

This is essentially what the J&J vaccine is, except it is purposefully made replication-incompetent. It's an adenovirus whose genome has been modified to 1) express the SARS-CoV-2 spike protein Edit: in its genome on its surface, and 2) not replicate in its human hosts.

Edit: I messed this up the first time around, so this is a clarification: the J&J vaccine is basically a delivery vehicle for the genetic information for the host cell to build the spike protein. The viral vector itself does not express the spike protein.

 

[BillTre]

The issue of releasing viable viruses into the nature to infect some particular animal (like mosquitoes) has come up before.

Here are a couple of posts:
Engineering to push the spread of modified viruses population in a virus population.
Having an election of Florida about whether to release engineered mosquito viruses.

 

[DaveE]

releasing viable viruses into the nature to infect some particular animal (like mosquitoes) has come up before.

Are you sure about this? I thought the mosquito stuff was gene drive (modification of the germ cells and transmitted via normal reproduction), not viruses. The only case that comes to my mind is Myxoma virus introduced in the Australian rabbit population, which wasn't an "engineered" virus, and didn't turn out well.

Anyway, I very curious about this and would appreciate any links to pursue.

 

[BillTre]

Are you sure about this? I thought the mosquito stuff was gene drive (modification of the germ cells and transmitted via normal reproduction), not viruses. The only case that comes to my mind is Myxoma virus introduced in the Australian rabbit population, which wasn't an "engineered" virus, and didn't turn out well.

Anyway, I very curious about this and would appreciate any links to pursue.

Opps. Yes your are right.

 

[DaveE]

I think the oral polio virus is an instructive example here. It is a weakened live virus vaccine which has been widely used. While not transmissible enough to exist without vaccination, it can be transmitted to others. There are also many cases where the transmission was detected because the virus reverted to some level of increased virulence and cause AFM in rare circumstances. For that reason it is no longer licensed in the US, where IPV is the vaccine of choice. However, IPV is harder to store and administer, so OPV is the vaccine of choice in 3rd world countries. It is believed that ultimate polio eradication isn't possible with OPV.

But this highlights two huge problems:
1) We don't know enough about transmission of viruses (immune system interactions), and the epidemiology of epidemics, to design a viruses that is reliably transmitted without vaccination. This is especially true if you desire any control over where or how much. This is why we use pre existing viruses as viral vectors (like the J&J adenovirus based COVID vaccine). I don't believe anyone has made a virus, we only know how to modify existing viruses.
2) Evolution. Specifically immune system evasion. If you succeed in launching this virus into the general population, you will have essentially no control over if or how it changes.

Finally, there is a huge political/PR problem. People don't even like GMO corn. There is already great concern for "gain of function" research as it is. A "lab generated" infectious virus would bring out every pitch fork owning protester in the suburbs. And without the regulatory apparatus to ensure adequate safety testing, I might be one of them.

The history of other biological controls and invasive species mishaps isn't promising.

 

[artis]

The appearance of the OMICRON variant appears to be more effective at (finally?) limiting the pandemic than the previous vaccinations.

Yes true, but I would like to point out that it is also partly because the naturally induced immunity has proved to be broader and longer lasting on average than vaccine induced one. So logically the latest and also more moderate Omicron given it's lower risk factor and much higher transmissibility is doing us a natural immunity boost whether we like it or not.
Just a study and a news article to base my claims , although hopefully they shouldn't be doubted given this is now public knowledge.
https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1.full.pdf

https://www.reuters.com/business/he...vaccination-during-delta-surge-us-2022-01-19/

I would tend to agree with @DaveE and others here that introducing a virus that is live and able to replicate into a population for the sake of immunity is essentially gambling.
I mean we are at the point where we can simulate certain proteins and parts of a virus on a computer but then imagine just the mammal population alone in the world and the biological "Petri dish" that it gives to a virus for both mutating and spreading, do we posses the tools to reliably predict the outcome of it? I don't think so.

What we could do and seem to be doing and I think it's the right direction is to make vaccines less vaccine like aka to have nasal sprays as vaccines etc , in forms that are more accessible and less "needle fear" inducing.
Minimize adverse/side effects, maximize production/availability and offer multiple "delivery" methods , preferably ones that can be done anywhere and safely. This alone I think would decrease vaccine hesitancy.

On a more PR/social psychology side I think the very short time scales at which everything happened was also a great contributor to hesitancy. People in general take time to get comfortable with certain new ideas/laws/rules etc.
I can say from the folks I know that those who protested the Covid vaccine and especially the mandate were absolutely fine with and all have had the "classical" vaccines like polio etc, their kids have been vaccinated and so on and so forth. So I think the fast pace of everything combined with political pressure worked against instead of in favor of vaccination. Just how society works from what I can see.

 

[Ygggdrasil]

Yes true, but I would like to point out that it is also partly because the naturally induced immunity has proved to be broader and longer lasting on average than vaccine induced one. So logically the latest and also more moderate Omicron given it's lower risk factor and much higher transmissibility is doing us a natural immunity boost whether we like it or not.
Just a study and a news article to base my claims , although hopefully they shouldn't be doubted given this is now public knowledge.
https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1.full.pdf

https://www.reuters.com/business/he...vaccination-during-delta-surge-us-2022-01-19/

Though the information you cite does seem reliable, I'm not sure there is absolutely no doubt about this issue. For example, here is what the CDC has to say on the issue, which suggests that vaccine-induced immunity provides more consistent protection than infection-induced immunity:

Key findings and considerations for this brief are as follows:

• Available evidence shows that fully vaccinated individuals and those previously infected with SARS-CoV-2 each have a low risk of subsequent infection for at least 6 months. Data are presently insufficient to determine an antibody titer threshold that indicates when an individual is protected from infection. At this time, there is no FDA-authorized or approved test that providers or the public can use to reliably determine whether a person is protected from infection.
  • The immunity provided by vaccine and prior infection are both high but not complete (i.e., not 100%).
  • Multiple studies have shown that antibody titers correlate with protection at a population level, but protective titers at the individual level remain unknown.
  • Whereas there is a wide range in antibody titers in response to infection with SARS-CoV-2, completion of a primary vaccine series, especially with mRNA vaccines, typically leads to a more consistent and higher-titer initial antibody response.
  • For certain populations, such as the elderly and immunocompromised, the levels of protection may be decreased following both vaccination and infection.
  • Current evidence indicates that the level of protection may not be the same for all viral variants.
  • The body of evidence for infection-induced immunity is more limited than that for vaccine-induced immunity in terms of the quality of evidence (e.g., probable bias towards symptomatic or medically-attended infections) and types of studies (e.g., observational cohort studies, mostly retrospective versus a mix of randomized controlled trials, case-control studies, and cohort studies for vaccine-induced immunity). There are insufficient data to extend the findings related to infection-induced immunity at this time to persons with very mild or asymptomatic infection or children.
• Substantial immunologic evidence and a growing body of epidemiologic evidence indicate that vaccination after infection significantly enhances protection and further reduces risk of reinfection, which lays the foundation for CDC recommendations.

https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/vaccine-induced-immunity.html

Of course, the guidance is older than the newer data you cite, so the CDC may revise this information in the future.

 

[hutchphd]

Has this been referenced here ?It is pretty new.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7104e1.htm#contribAff

My takeaway (graph at the end) is that infection and vaccination are both very good at prevention of severe disease, with infection being slightly better. Also infection+vaccination is no better than infection alone.

 

[artis]

Has this been referenced here ?It is pretty new.
https://www.cdc.gov/mmwr/volumes/71/wr/mm7104e1.htm#contribAff

My takeaway (graph at the end) is that infection and vaccination are both very good at prevention of severe disease, with infection being slightly better. Also infection+vaccination is no better than infection alone.

@Ygggdrasil @hutchphd beat me to it but I wanted to cite the same study which was also one of the studies I based my claims upon although I did not cite it at my post.

The only question remains about length/duration of immunity from natural infection vs vaccination.

 

[Mike S.]

"Designer viruses" is perhaps a poor way to phrase it for PR reasons. Let's say "live attenuated vaccine". Note that the better you hobble the virus not to be dangerous, the more likely that every kid is going to need his own little sugar cube. Which is perhaps just as well in many countries where vaccine development is left to private companies that have zero interest in a product that gives itself away. There are quite a few papers that discuss live attenuated vaccines, for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354792/ .

Nonetheless, the experience from polio is that a "live vaccine" can become a dangerous outbreak. That shouldn't happen in a country with good vaccine coverage, but it can happen where there are many susceptible people. ( https://www.cdc.gov/vaccines/vpd/polio/hcp/vaccine-derived-poliovirus-faq.html , https://abcnews.go.com/Health/wireStory/polio-cases-now-caused-vaccine-wild-virus-67287290 ). Playing with viruses is much like playing with fire, for the same reasons; still, civilization wouldn't be what it is without fire.

There is much I haven't seen about SARS-NCoV-2 that I would like to. What happens if, say, the small E protein is completely excised from its genome? Can it recover (revert) from that effect? Even an ongoing pandemic that has wracked the world has not inspired countries to fund the level of research we should be doing routinely on any pathogen that threatens the world.

 

[BillTre]

Even an ongoing pandemic that has wracked the world has not inspired countries to fund the level of research we should be doing routinely on any pathogen that threatens the world.

How do you know this?

 

[hutchphd]

This admittedly was an ill-formed question (my apologies) , but I know precious little about this technology.
I was interested in a truly dire situation: like perhaps a new virus that produces 50% mortality and has an R₀ of 10 and a 1 week incubation. It would seem to me that any conventional vaccination regime would be ~useless in this circumstance. Is it desirable to try to develop (or further develop?) the capability to produce a much less lethal but very transmissable immune dopplegangar virus at our command? Do we know how to do this (or where to start)? The obvious example here is the COVID 19 Omicron variant or perhaps (for Edward Jenner) a much more transmissable Cowpox. I am assuming this conversation is not novel, but I find myself surprisingly ambivalent.and ill-informed. Make the virus and spray it at the airport and the subway?

 

[TeethWhitener]

To the best of my knowledge, it is not currently possible to determine a priori a virus’s transmissibility or virulence. As I mentioned earlier, any virus that can replicate can mutate, potentially to a more virulent form. Also, even if I could get beyond the ethical issues of releasing an experimental virus on an unsuspecting public, I’m not sure what it gains you. Presumably it would have to go through the same testing and approval that a standard vaccine would.

I suppose you’re trying to overcome vaccine hesitancy, but as I mentioned, if the virus had a very high mortality rate, I suspect that vaccine hesitancy would magically evaporate. I have no proof, but I imagine that people who know folks that have died of COVID are probably more likely to get vaccinated and take other precautions (what little info I found on google claims that roughly 1 in 3 people know someone who has died of COVID: Link). In the case where a pathogen had a very high infectivity and mortality rate, a lot more people would know someone who had died, and a lot of people would know a lot of people who had died.

 

[hutchphd]

I was thinking of a a more dire circumstance where dissemination of a live aggressive but far less lethal virus might be the only course of action (Less lead time, very little infrastructure to disseminate, very cheap and egalitarian once released, and high coverage). Could such a thing be possible in a forseeable near futue? Can a moral case be constructed to start down that road ? This to forestall a truly cataclysmic pandemic...

 

[DaveE]

How would you do clinical trials with a highly transmissible virus? If you skip them, how would you know if it's safe and effective?

 

[TeethWhitener]

I was thinking of a a more dire circumstance where dissemination of a live aggressive but far less lethal virus might be the only course of action (Less lead time, very little infrastructure to disseminate, very cheap and egalitarian once released, and high coverage). Could such a thing be possible in a forseeable near futue? Can a moral case be constructed to start down that road ? This to forestall a truly cataclysmic pandemic...

Again, currently the only way to know how transmissible and virulent a pathogen is is to let it infect a bunch of people and record the results. Unless you already know at the onset of an epidemic 1) that pathogen A offers cross-protection against pathogen B, and 2) that pathogen A is less virulent than pathogen B, you’re flying blind.

 

[hutchphd]

The technology would need to be robust and the trials "quick and dirty" I think. Some deserted location. The alternative is truly dire in my hypothetical...Billions of people in months. How clever can we get at this technology?

 

[Drakkith]

This admittedly was an ill-formed question (my apologies) , but I know precious little about this technology.
I was interested in a truly dire situation: like perhaps a new virus that produces 50% mortality and has an R₀ of 10 and a 1 week incubation. It would seem to me that any conventional vaccination regime would be ~useless in this circumstance. Is it desirable to try to develop (or further develop?) the capability to produce a much less lethal but very transmissable immune dopplegangar virus at our command? Do we know how to do this (or where to start)? The obvious example here is the COVID 19 Omicron variant or perhaps (for Edward Jenner) a much more transmissable Cowpox. I am assuming this conversation is not novel, but I find myself surprisingly ambivalent.and ill-informed. Make the virus and spray it at the airport and the subway?

Assuming you could develop such a virus faster than you could develop a vaccine, then such an idea is certainly plausible. But probably not possible in the near future given our current knowledge and technology.

 

[Drakkith]

The technology would need to be robust and the trials "quick and dirty" I think. Some deserted location. The alternative is truly dire in my hypothetical...Billions of people in months.

I'm a bit more optimistic. The Covid-19 pandemic shows that when people actually follow proper social distancing, lockdown, and other safety measures the rate of infection is dramatically reduced. If there's a pandemic that's so deadly that people are essentially dying in the streets then I'm confident that people would take these safety precautions MUCH more seriously than the did during covid-19.

 

[TeethWhitener]

The technology would need to be robust and the trials "quick and dirty" I think. Some deserted location. The alternative is truly dire in my hypothetical...Billions of people in months. How clever can we get at this technology?

How about this? It’s a heck of a lot easier to roll out tests than vaccines or therapies. Roll out massive testing, test everyone at gunpoint, and if they have the disease, kill them. It would probably ultimately save more lives than your method. It uses existing technology. It’s quick.

It’s also morally abhorrent. Can a moral case be constructed to start down that road? What if we only load 10% of the guns? What if instead of using guns we engineer a pathogen about which we know nothing and spray it unwillingly on people?

 

[hutchphd]

But probably not possible in the near future given our current knowledge and technology.

How soon if we pushed it? Do we know enough to hazard a guess? Decades? Centuries? My guess is 3 decades. Part of me thinks our response to a truly dire pandemic would be far less accommodating to science than the present one. Unfortunately we are in this together. So it will be availible for my centenary birthday...

How about this? It’s a heck of a lot easier to roll out tests than vaccines or therapies. Roll out massive testing, test everyone at gunpoint, and if they have the disease, kill them. It would probably ultimately save more lives than your method. It uses existing technology. It’s quick.

It’s also morally abhorrent. Can a moral case be constructed to start down that road? What if we only load 10% of the guns? What if instead of using guns we engineer a pathogen about which we know nothing and spray it unwillingly on people?

I can think of many immoral alternatives but that says nothing at all (yours is actually an ad hominem argument). Please don't mischaracterize what I said. This is a real issue perhaps subject to rational discourse.

 

[TeethWhitener]

I can think of many immoral alternatives but that says nothing at all (yours is actually an ad hominem argument). Please don't mischaracterize what I said. This is a real issue perhaps subject to rational discourse.

No, it’s an argument by analogy. Please attempt to engage in rational discourse. The only difference between my scenario and yours is that at least the guns are tested. With a pathogen, you have no idea how many people you’re going to have to kill before you hit upon a variant that is less virulent and more transmissible. I have already said at least twice that there is no way to determine a pathogen’s virulence and transmissibility without infecting a lot of people with it. I’m not sure how much clearer I can be.

 

[artis]

Alot of questions arise here,

For one I agree with the opinion expressed that for a more deadly virus people would actually seek out ways to protect themselves more, with Covid many got away with few days of sweat and watching movies while out of work, sure enough such folks might be less interested in vaccination or other medical interventions.
If economics is any measure then the law holds, the more something is needed the more it is sought after.

Now as for the OP scenario , first of all is there even a virus alive today or known to us that could (given our modern medicine and ways of protection) be so lethal as to kill billions in a matter of weeks? I think natural virus, not a biological weapon designed to destroySecond of all this vaccine spraying I can already see so much wrong with it apart from the horrible ethics and bad PR, first of all how do you control for dose? How ca you even attempt to control for dose for something that gets sprayed into a public space?
Then for example how do you not give the vaccine to someone who is already infected therefore causing a double burden on ones immunity?

Anyway if you cannot control the dose you either risk having no effect at all or overboosting someone to the point where they might develop serious side effects or die.

 

[hutchphd]

I have already said at least twice that there is no way to determine a pathogen’s virulence and transmissibility without infecting a lot of people with it. I’m not sure how much clearer I can be.

Obviously I am not advocating randomly generating pathogens and spraying them willy-nilly. The question is whether we can obtain the ability to control those aspects of viruses: hence the term "designer viruses" and not "madman mutated viruses". I am fully aware that this is (yet another) terribly slippery slope.

Now as for the OP scenario , first of all is there even a virus alive today or known to us that could (given our modern medicine and ways of protection) be so lethal as to kill billions in a matter of weeks? I think natural virus, not a biological weapon designed to destroy

I have no idea, but certainly our everincreasing proximity and connectedness makes the effects of pathogens more potentially lethal. Also there may be new avenues for intermixing of viral DNA (I'm way out of my depth here) which are thereby afforded. These Corona viruses (MERS SARS COVID (different flavors) and HIV seem to have suddenly "appeared"

Second of all this vaccine spraying I can already see so much wrong with it apart from the horrible ethics and bad PR, first of all how do you control for dose? How ca you even attempt to control for dose for something that gets sprayed into a public space?
Then for example how do you not give the vaccine to someone who is already infected therefore causing a double burden on ones immunity?

Presumably the "dose" would be simply a sufficiency to produce (mild and therapeutic ) disease. The idea is that this would then be communicable. The severity of most disease is only very loosely correlated to initial viral load past threshold I believe. The increasing of immune response might be a clinical issue but it could be beneficial.
As to the ethics: that is the crux of this discussion. Given the (IMHO possible) scenario do we demand societal ethics that preclude this form of intervention. Is it "horrible" to try to salvage civilization from a new dark age? How far do you go down this road ? These are discussions we should have before it is too late to decide.

 

[TeethWhitener]

Alright I’ve calmed down a bit. Apologies to @hutchphd for getting heated.

One approach that is related but which I find significantly more ethically palatable is based on the fact that it’s really quite a fast process (or at least it can be) to prototype RNA vaccines. Once the genome of a pathogen is known and understood, modified RNA sequences corresponding to promising immunological targets can be synthesized and rolled out in a matter of days to weeks. (If I recall correctly, Pfizer had a prototype vax within 2-3 days of the publication of the SARS-CoV-2 genome sequence.) If a situation arose which were as dire as you lay out, I could condone a scenario where an RNA vax were rolled out untested to the (willing) general public, with the caveat that it is untested and the requirement to be monitored for possible exposure/vaccine efficacy. Basically, the entire vaccine rollout would be one big clinical trial.

One bottleneck would be synthesis of vaccine material, but oligonucleotide synthesis is largely automated now, so one could dream up mass manufactured black boxes to synthesize the requisite RNA in a distributed fashion at scale.

All of this technology is either already available or very near-term and already in exploratory phases for a number of applications. In the long run, a priori prediction of virulence and transmissibility is a worthy goal, but my gut feeling is that it’s either 1) 50 years away, or 2) pending some machine learning breakthrough (so much closer than we anticipate).

 

[hutchphd]

I agree that the bioethics questions are extraordinarilly difficult. Hopefully airing them in a proactive manner will produce more "light" and less "heat' (@TeethWhitener I don't mind a spirited discussion so no apology necessary.)

 

[Mike S.]

For purposes of discussion, let's direct this question to a more tangible and immediately doable case.

I just ran into someone who had been working hard to go into nursing, who changed major because the program had ... surprised her with a vaccination requirement. I was rather flabbergasted ... she said something about religion, but citing other religions, not saying it was her religion, and about concern about the vaccine.

I didn't think that was the right call on her part -- NONETHELESS, her call it is.

Now I understand you can't risk people spreading COVID to cancer and transplant patients and the old and HIV-positive or someone about to go into surgery ... I mean, I understand that you'd have to test an unvaccinated nurse almost every day and it's not practical or necessarily reliable anyway. I understand why they can't let her in. But ... there is still a way, for the person with a determined religious objection.

We could get the last few omicron patients in the county to submit samples, which we dilute out to what we think is a least infectious dose, and we could offer the refuseniks the option to infect themselves with a "mild" strain of COVID, like an inoculation you could say. Do that N times until they stop getting sick, and if they are still able to stay on their feet all day without chronic fatigue, we can let them do nursing.

Now, it seems like we should do this, I think, whenever they are willing to participate, because we can infect them and isolate them and then let them live their lives, rather than leaving them to run around the countryside like unexploded ordinance, never knowing when they're going to "go off" with an unexpected infection. At least in this scenario we don't have to consider the effects of indirectly infecting anyone but the people we are thinking of.

Yea or nay?

 

[Drakkith]

Yea or nay?

Nay. Nay. Nay. There is no reason to jump through hoops to let people get around a vaccine requirement for a nursing job when a new infection could crop up at anytime that would require new vaccines that they also wouldn't accept. So you'd just lose staff as soon as a new outbreak happens or constantly have them putting people at risk because they refuse to get vaccinated.

Many jobs have health or safety requirements. If you don't want to follow those requirements, you can choose to work somewhere else or in another career that doesn't have them. If you don't want to wash your hands, don't work in a kitchen. If you don't want to wear a hard hat and PPE (and people complain about mask requirements in jobs... psh...) then don't work in construction or in an industry that requires those things. If you don't want to follow rules on how to safely operate heavy machinery, don't work somewhere that requires you to operate a forklift, crane, or other heavy equipment.

 

[hutchphd]

I didn't think that was the right call on her part -- NONETHELESS, her call it is.

By what notion (legal or moral) do you make this EMPHATIC statement ?
It is truly absurd.