I'm working on a novel, in which a character was given a cutting edge vaccination to a deadly disease. She is now valuable because she was the only one given the vaccine and the research to make more is unavailable. Now some people want to "reverse-engineer" the vaccine by studying her (the one who created the vaccine is gone, by the way).

So...my question is: Is it possible to formulate this vaccine by simply using a blood or tissue sample, or would the character herself need to be available for research?

I'm not a scientist, so I'm only guessing (well, researching and guessing), that it's even possible to reverse-engineer a vaccine. Appreciate any input!

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    $\begingroup$ A vaccine is not a cure. It won't help if the person has already contracted the disease. What is a vaccine does is prevent contracting the disease in the first place. $\endgroup$ – AlexP Jun 25 '19 at 5:57
  • $\begingroup$ Thank you, AlexP, I'll edit my wording. $\endgroup$ – cal Jun 25 '19 at 10:53
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    $\begingroup$ Swap "deadly disease" with "snake and spider venom", and your character with a horse or rabbit, and you have the exact story of how snake and funnelweb spider anti-venom is made in Australia. So the method also works against toxic proteins. (don't worry - funnelweb spider venom is only lethal to primates - the rabbits don't suffer from the venom at all). reptilepark.com.au/venom-program $\endgroup$ – Jason Jun 25 '19 at 11:00
  • $\begingroup$ That was a knock-your-socks-off cool read! Thank you, Jason. $\endgroup$ – cal Jun 25 '19 at 11:30
  • $\begingroup$ It's mind-blowing stuff. Since the technology matured in 1982, there hasn't been a single death in Australia due to spider bites. $\endgroup$ – Jason Jun 25 '19 at 23:15

It's quite a bit more difficult than the other answers make it out to be.

First, we need a rough draft of what kind of immunity we're dealing with. Often, with vaccines it's humoral immunity (antibodies and B-cells). This is what the existing answers are talking about. An alternate type of vaccine, for example, would be a T-cell inducing vaccine, and these are generally a whole lot more complex.

Let's say we're talking about humoral immunity, and are not getting into the more experimental types of vaccines.

We can go through the list of vaccine types, and discuss if there's a potential benefit of having an immune individual (basic description of vaccine types found here)

  1. Live-attenuated vaccines

    Mostly useless, since there's no way to track down how to attenuate the pathogen from an immunized individual. Possibly, we could use serum of the individual to see if the attenuated pathogen is still immunogenic by testing if the subject's serum still binds the pathogen, but that's unreliable and animal testing is likely more reliable. The rare exception is if the attenuated variant occurs naturally, as was the case with cow pox, the first vaccine.

  2. Inactivated vaccines

    Very useless, the main challenges here are truly inactivating the pathogen while keeping the vaccine immunogenic and exposing representative surface proteins. Our subject is not going to help at all with these challenges.

  3. Subunit, recombinant, polysaccharide, and conjugate vaccines

    Somewhat useful, our subject can help us identify the subunit or polysaccharide used (as discussed in the answer by Willk). That still leaves us with the challenge of creating a vaccine that forms the right type of immunity against this subunit or polysaccharide. Recombinant and conjugate vaccines are more complicated, since the targets are artificially created, and we can only test if we have "the right one".

    Also note that quite often, multiple antigens are used in a single vaccine of these types, and a single person might only respond to a fraction of the antigens. In that case, the person can be immune, while it's impossible to track down all the antigens used, and making a vaccine only based on the antigens that induced immunity in this person might have a much lower efficacy than the original vaccine.

  4. Toxoid vaccines

    Toxoid vaccines are vaccines against a specific toxin, and generally somewhat easy to create if you have a toxin in mind that constitutes a real health problem. Our subject might be able to help, but it's unlikely that would be necessary, since the toxin would've already been identified.

Our subject can also give us a hint which kind of vaccine was used. Types 1 and 2 will likely produce a more diverse antibody repertoire than 3 and 4. But this will likely be inconclusive, since we only have a single subject.

For a more thorough read on vaccine types, I recommend this NIH webpage. Be sure to read into adjuvants and their role in vaccines too. If you have a specific type of vaccine in mind, I can try to elaborate on the possible role of samples from an immunized patient in reverse-engineering the vaccine, but generally, that role is going to be pretty limited.

An interesting experimental vaccine type to name in this context might be DNA vaccines, because this is one of the few types where there might be an actual major benefit to having an immunized individual with a specific vaccine. If he/she were to be vaccinated using a DNA vaccine, we could try to identify and culture the immunogenic cells by exposing them to the pathogen, and then fully sequencing the immunogenic cells, compare with the overall genome of that person, and possibly identify the sequence used in the vaccine (it would be a sequence expressed significantly more in immunogenic cells). That would still leave us with identifying adjuvants used.

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    $\begingroup$ Thanks for the info, Erik A. Your answer (and some ensuing reading) has definitely confirmed my suspicions that the science is pretty complicated. May I ask -- given the scenario described in my question, would reverse-engineering be more feasible if the subject was available, or if she just supplied a blood sample? $\endgroup$ – cal Jun 26 '19 at 2:48
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    $\begingroup$ @cal Not really, but it would open up the possibility of creating a human hybridoma, an antibody-secreting tumor that can be transplanted in animals for large-scale antibody production. Wikipedia has an overview on the basics for mouse hybridomas. A similar technology exists for human hybridomas. This is not reverse-engineering the vaccine, but only allows us to create antibodies (passive vaccines). Depending on the technique used, a spleen sample, bone marrow sample or even blood sample might also be sufficient for creation of a hybridoma. $\endgroup$ – Erik A Jun 26 '19 at 6:32
  • $\begingroup$ Okay, cool. I'm actually trying to move the plot so that the subject would be needed (not just a sample, in other words). Do you know of a situation in which this could be scientifically feasible, without too much hand-waiving? $\endgroup$ – cal Jun 26 '19 at 12:30
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    $\begingroup$ [1/2] If you go for the hybridoma thing, there are many, many difficulties one can encounter creating one. Say they try it first on blood, then fail, and then want a spleen biopsy for higher B-cell counts, that's not very hand-wavy and they'd need to operate your subject for that. They can, of course, use all the material taken, and still fail at making a proper hybridoma thus needing to take another biopsy. $\endgroup$ – Erik A Jun 26 '19 at 12:36
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    $\begingroup$ Human-human hybridomas are pretty difficult things with many variables. You essentially need to merge your subject's cells with tumor cells of a different subject, while keeping the cells viable and producing antibodies, select out the cells producing the desired antibodies, culture them, then transplant them to animals while keeping them alive, and then harvest the antibodies produced by the animals. Many points of failure (and potential drama), and keeping your subject alive, happy and willing to undergo extra surgery might be a good thing $\endgroup$ – Erik A Jun 26 '19 at 12:39

Here is a general way one could do it.

  1. Get samples of pathogen. Break it up into small bits. Fix bits to plate.

  2. Wash pathogen bits with your characters serum. Then wash it off and add a marker to plate that binds to human antibodies.

That is an ELISA test; old tech.



The vaccine has protected her: she has protective antibodies. Now you know what component(s) of the pathogen she has antibodies to and so which ones are important for immunity.

Maybe you have unlimited quantities of the pathogen. You could use that component of the pathogen by itself as a vaccine or make a vaccine around it. Or you could use that component of the pathogen to raise a bunch of antibodies in animals, and see what similar things those antibodies also stick too. Then use one of those similar things to build a vaccine.

This makes building a vaccine sound trivial. It is not. But maybe this would be plausible enough for a fiction.

  • $\begingroup$ Are you sure you understood the question correctly? Step two mentions "your characters serum" . But as far as I understand the question, the character doesn't have a serum. They were administered a vaccine and now have antibodies in their blood. Or does that make their blood a serum against the pathogen? $\endgroup$ – Philipp Jun 25 '19 at 12:52
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    $\begingroup$ @Philip: "Serum" is the name of the liquid component of the blood without the clotting factors. That is, serum is blood minus red and white cells, platelets, coagulation factors etc. Plasma is serum plus fibrinogens. $\endgroup$ – AlexP Jun 25 '19 at 13:04
  • $\begingroup$ I added an additional idea to my original question. Thanks for the thoughts, guys. $\endgroup$ – cal Jun 25 '19 at 14:05
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    $\begingroup$ You're making leaps. Let's say we make an ELISA like you described, antibodies bind to it, yay, but that doesn't give us a clue what components provide immunity. We would first need to decompose the pathogen in different surface-expressed components, mass-produce these components and make specific ELISAs for each component. Which is not a minor task and might require years of research. Even then, if the original vaccine was either live-attenuated or inactivated, the test will likely be positive on many components and have provided no information but a clue about the type of vaccine used. $\endgroup$ – Erik A Jun 25 '19 at 14:20

Yes, with a blood sample.

You can achieve a 'kind of' immunity. I'm just going to quickly break down how vaccines work for background, just in case. Vaccines, in general, are a weak version of the target pathogen (usually a bacteria) which the body 'trains' against and figures out how to create a proper antibody. (Bit more complex than that, but it's good enough for now.) Inside your character's body, there no longer exists the vaccine she was injected with. But there are antibodies, which can fight off the virulent strain of the disease, that is, the disease at full strength.

Based off that, the 'cure' you're looking for is just the concentrated dose of said antibodies. Regularly injecting them into any patient would fight off the disease. The trick, of course, is getting those antibodies. Willk's suggestion for analyzing the antibodies is perfectly valid. But there's also another way. And that lies within said character's B lymphoblastic-cells within their blood that produce said antibody. If you remove, isolate, and culture them, you can inject the B-cells into the victim's body, giving them factories to produce their own antibodies. This is based off research here. (There should be a few other places if you look for yourself, I just searched Spanish Flu because I remember reading up on these kind of experiments being done with it.)

  • $\begingroup$ "usually a bacteria": The first five diseases I searched for which have an effective vaccine are caused by viruses, not bacteria. (Measles, mumps, rubella, smallpox, polio.) I am pretty sure that vaccines are almost exclusively anti-viral. $\endgroup$ – Martin Bonner supports Monica Jun 25 '19 at 12:20
  • $\begingroup$ OK, so according to this answer you can manufacture a cure or even a vaccine from the blood of the person. But what if you only have a limited quantity of blood available? Does that limit how much cure/vaccine you can make? $\endgroup$ – Philipp Jun 25 '19 at 12:54
  • $\begingroup$ Your second option is nonsense imo. If you inject an individual with nucleated cells of another individual, what's most likely going to happen is that he's going to produce antibodies against those B-cells, they'll die, and nothing else. If you add antirejection medicine, you're likely worsening immunity. Obtaining sufficient amounts of antibodies from a single patient to provide passive immunity to even one other patient is likely not feasible, unless you have a way to significantly boost antibody production. $\endgroup$ – Erik A Jun 25 '19 at 14:13

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