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A vaccine essentially simulates an infection so that our body produces antibodies against it & thus helps when we actually get infected in the future.

But for some diseases, we see post exposure vaccination - for e.g. Tetanus & Rabies.

How can this work? If the pathogen is already in our body, then our immune system would produce antibodies against it just like it would against the vaccine. So what is the point.

I found this paper which is an attempt.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159179/

They say this for tetanus

However, postexposure vaccination against tetanus produces an adequate amount of antitoxin in just 4–7 days, leaving a small window for a postexposure vaccine to outpace the natural, 10-day incubation

However, this explanation doesn't make sense to me consider what incubation period means

https://en.wikipedia.org/wiki/Incubation_period

Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent. In a typical infectious disease, the incubation period signifies the period taken by the multiplying organism to reach a threshold necessary to produce symptoms in the host.

Is the number of viruses delivered by a vaccine higher the number of viruses it would replicate into in an actual infection by the end of the incubation period? I couldn't find any place - the number of actual live/attenuated/dead viruses delivered by a vaccine.

And this is explanation is given in the link only for tetanus, they say they don't understand why or how post-exposure vaccination works for Rabies.

Have there been trials done where they tried only immunoglobin or only vaccine to see if both are required & if yes, which has a bigger effect - the vaccine or the immunoglobin?

I understand that the Rabies virus is a stealth virus. The body/immune system can't detect it till it reaches the brain. So is this changed in the rabies vaccine? Does the body/immune system detect the Rabies virus delivered by the vaccine - if yes, what change has been done in the virus so that it is no longer a stealth virus?

UPDATE:

  1. One of the comments also referred to the above bold part. This seems to be a very plausible reason. Are there any sources for this - i.e. that reason why Rabies virus is not detected by Immune System doesn't happen in the Vaccine with the Virus. If yes, then how exactly is the stealth mechanism missing in the virus in the vaccine.

  2. I read a little more about Tetanus Vaccine. Tetanus vaccine is a weak Toxoid rather than inactivated Pathogen. So I am guessing the reason why it works is probably because it takes the bacteria from the infection a few days to produce the toxins which cause Lockjaw. So if the Toxoid contains a suppressed form this same Toxins then the body can mount in immune response earlier. Is the above reason correct as to why Tetanus Vaccine works Post Exposure?

user93353
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    You'll never see human trials with rabies treatments because it's a 100% lethal disease. Withholding the vaccine would be highly unethical, criminal even. And tetanus is no pud disease either. When we have a treatment that's proven to work, why would anyone put people at risk to answer merely academic questions? There are probably animal studies addressing your questions. – Carey Gregory Feb 16 '24 at 05:02
  • @CareyGregory - the main question here how can a live/attenuated virus produce some response which the real virus couldn't – user93353 Feb 16 '24 at 05:18
  • I understand that. I was only commenting on your last paragraph asking about trials. – Carey Gregory Feb 16 '24 at 15:03
  • One more thing to consider, a live bacteria has defence mechanisms which resist getting recognised by host immune system which the tetanus toxoid does not have - so in theory the exposure of toxoid to the immune system is much higher than the bacteria itself. In the case of viruses, they are obligatory intracellular organisms, which would mean even poorer exposure to the immune system while a inactivated virus is fully exposed. – One Face Feb 18 '24 at 14:28
  • https://asm.org/articles/2018/december/microbial-ninja-warriors-bacterial-immune-evasion#:~:text=Bacteria%20are%20multifaceted%20in%20their,or%20even%20mimicking%20host%20molecules. – One Face Feb 19 '24 at 00:40
  • https://www.ncbi.nlm.nih.gov/books/NBK27176/#:~:text=One%20way%20in%20which%20an,antibody%20against%20their%20surface%20structures. – One Face Feb 19 '24 at 00:42
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    @user93353 You're being unnecessarily argumentative with every person who tries to help you. Please stop doing that. – Carey Gregory Feb 19 '24 at 03:57
  • Comments have been moved to chat; please do not continue the discussion here. Before posting a comment below this one, please review the purposes of comments. Comments that do not request clarification or suggest improvements usually belong as an answer, on [meta], or in [chat]. Comments continuing discussion may be removed. – Carey Gregory Feb 19 '24 at 04:00

1 Answers1

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A vaccine essentially simulates an infection so that our body produces antibodies against it & thus helps when we actually get infected in the future.

Sometimes and sometimes not. That's a good way to look at it for immunization purposes but not for post-exposure prophylaxis.

The point is pretty clear in the body of your question. Using your example, it takes the bacteria that causes tetanus 10 days of replicating (making a toxin in the process) before we start to get sick. By that time, we will have started mounting a response, but if we have not been vaccinated, the bacteria that causes tetanus will have started producing the toxin in amounts greater than our ability to destroy it.

If we have been vaccinated, we have lymphocytes already geared towards making antitoxins (antibodies directed against the bacterial toxin). Giving us inactivated tetanus toxin (toxoid) stimulates the primed lymphocytes to produce antitoxin faster than the bacteria can produce it. The body's response to the vaccine outpaces the ability of C. tetani to make toxin. (If someone has never been vaccinated against tetanus, we still give the vaccine, but in multiple doses to amp up antitoxin production.)

For rabies, it's different. The vaccine itself doesn't protect us sooner than the virus would kill us. (Please see Edit.) For that reason, we must also give Human Rabies Immune Globulin (HRIG) to try to kill whatever amount of virus we may have been infected with. So, in effect, the answer to your question

Is the number of [inactivated viruses or virus particles] delivered by a vaccine higher the number of viruses [that would need to replicate] into in an actual infection by the end of the incubation period?

is, "Yes." We don't give the live virus; that would kill us every time. But we do get pumped full of the innocuous killed virus.

Have there been trials done where they tried only immunoglobin or only vaccine to see if both are required & if yes, which has a bigger effect - the vaccine or the immunoglobin?

No. All we have is some data from areas that have no or poor access to RIG, which shows that prompt vaccination and good wound care is sufficient for many bites. There is no information on RIG alone, as it's very expensive and the vaccine is widely available and known to help. Withholding it would mean unnecessary deaths.

Edited to add: @jpa pointed out that the efficacy of vaccine alone is much better than I had realized. In countries without adequate amounts of human or equine rabies immune globulin (HRIG is very expensive), early vaccine (inexpensive) plus prompt good wound care is adequate, however, not 100%. In India, there are ~20K deaths/year from rabies, some of which are treatment failures. From one paper:

Treatment failures, when vaccine only is used, are more common when there are multiple bites or deep punctures at locations where there are many peripheral nerves such as on face and hands.

anongoodnurse
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