HS bio refresh pt 3. The wrap up! VACCINATIONS.

Updated: Aug 15, 2021

OK. Here we are. The grand finale. Everyone's favorite topic. The topic about which everyone is suddenly an expert. Or, at least, the topic in which many people are suddenly interested. I'm going to keep it simple and discuss the basics, just like in the last two posts about viruses, herd immunity, and the immune system. At the end, we'll see if we can tie it all together neatly and present it as a nice little package. Because who doesn't like presents?

What is the purpose of a vaccination? Why even bother? Why not just get the disease naturally, allow your body to make the antibodies naturally, and then fight off the infection naturally in the future?? Isn't natural better?

Ok sure. Go for it. I'm right behind you. You go first. Why don't you raise your hand to step on that fat, juicy, rusty nail, inoculate your foot with Clostridium tetani, wait the 3-21 day incubation period while crossing your fingers hoping you don't get lockjaw or painful spasms in other muscle groups in the neck, trunk, and extremities and generalized, seizure-like activity or convulsions in severe cases which may lead to a prolonged hospitalization, pulmonary embolisms, and death. I'll just be over here getting my tetanus shot. You see, the trick is that you have to actually survive the illness in order for you to reap the benefits of the antibodies you develop from the natural disease. That might work for diseases like, say, chicken pox. That might not work for a disease like Meningococcal meningitis. Meningococcal meningitis is a bacterial form of meningitis (a serious infection of the lining that surrounds the brain and spinal cord) associated with high fatality (50% when untreated). The onset of disease is rapid and the incubation period is short (on average only 4 days). Even when the disease is diagnosed early and adequate treatment is started, 8% to 15% of patients die, often within 24 to 48 hours after the onset of symptoms. Remember, the trick to reaping the benefit of those NATURAL antibodies is that you actually have to survive the disease first. Good luck with that. I'll be over here getting my meningococcal vaccination.

The purpose of a vaccination is to confer acquired immunity against a specific foreign enemy pathogen by stimulating the immune system. Huh? It's to get you to make antibodies to a specific antigen without the "getting sick" part. Whoa. Pretty slick, huh?! How does that work? Ok. Let's start to bring in things we've just reviewed.

Remember this?

  1. Gross virus particle lands in your nose and mouth.

  2. Military defense unit 1 (innate immunity)- skin, hair, mucus, cough, sneeze, etc. IT FAILS. Lame.

  3. Military defense unit 2 (still innate immunity)- Operation inflammation steps up. White blood cells, mast cells, macrophages, interleukins, cytokines. Yasss, team! Win that war! Beat that enemy. Oh, and go ahead and make those antibodies to that gross virus particle so next time, We. Are. Prepared.

  4. Fast forward. It's Next Time. Gross virus particle comes back for more. Nope. Not this time bud.

  5. We wake up that acquired immunity and tell those memory cells to make those antibodies and mark that gross virus particle for destruction. We're coming for ya. Target visualized. Missile launched. Disease averted. Mission accomplished.

How do vaccines work?

Remember, the purpose of vaccinations is to stimulate your immune system to produce antibodies. There are different types of vaccinations that do this.

Live, Attenuated Vaccines

Weakened, or attenuated, vaccines consist of live viruses that have lost the ability to cause serious illness but retain the ability to stimulate immunity. Examples of live, attenuated vaccines include: Measles, mumps, rubella (MMR combined vaccine), Varicella (chickenpox), Influenza (nasal spray), Rotavirus, Zoster (shingles), Yellow Fever.

Killed, Inactivated Vaccines

Vaccines that contain viruses that have been killed or inactivated with heat or chemicals. Inactivated vaccines elicit an immune response, but the response often is less complete than with attenuated vaccines. Because inactivated vaccines are not as effective at fighting infection as those made from attenuated viruses, greater quantities of inactivated vaccines are administered. Examples of inactivated vaccines include: Rabies, hepatitis A, influenza (shot), IPV (polio shot)

Toxoid (inactivated toxin)

Some bacterial diseases are not directly caused by a bacterium itself, but by a toxin produced by the bacterium. One example is tetanus: its symptoms are not caused by the Clostridium tetani bacterium, but by a neurotoxin it produces (tetanospasmin). Immunizations for this type of pathogen can be made by inactivating the toxin that causes disease symptoms. Examples of toxoid vaccines include: Diptheria, Tetanus (part of the DTaP combination vaccination)

Subunit/conjugate vaccines.

These vaccines use only specific parts of the pathogen, not the entire pathogen. And since only the bare minimum is used to stimulate an immune response, these vaccines typically have lower risks of adverse events and can be used on almost everyone who needs them, including people with weakened immune systems. One limitation of these vaccines is that you may need booster shots to get ongoing protection against diseases. Examples of subunit/conjugate vaccines include: Hepatitis B, Influenza (injection), Haemophilus influenza type b (Hib), Pertussis (part of DTaP combined immunization), Pneumococcal (Prevnar), Meningococcal, HPV.

Recombinant vaccines.

In the late 1980s, recombinant DNA technology was used to develop the first recombinant protein vaccine, the hepatitis B vaccine. Recombinant vaccines are made using certain "manufacturing" cells such as harmless bacterial or yeast cells. A small piece of foreign enemy pathogen DNA is inserted into one of those manufacturing cells. For example, to make the hepatitis B vaccine, part of the DNA from the hepatitis B virus is inserted into the DNA of yeast cells. Those poor schmuck yeast cells don't know one DNA from another DNA, so the yeast cells just start producing proteins encoded by whatever DNA is around. Well, sure enough, that sneaky little piece of enemy pathogen DNA gets its code made into a little enemy protein that is then displayed on the outside of that yeast cell and voila! Now, that sucker yeast cell just made a surface protein of the hepatitis B virus. You schmuck. Well, now that surface protein is purified, separated from the schmuck yeast cell (thanks for the help!! couldn't have done it without you!) and is now used as the active ingredient in the vaccine. So we now have hepatitis B virus surface proteins without actually needing an entire viral particle at all. All we needed was one tiny little strand of hepatitis B DNA. Sneaky.

Viral Vector Vaccines.

Ok. We're going to get a little tricky here. Stay with me. You know all of this information already but we're going to go back just a bit so that we can really understand what a viral vector vaccine is.

Remember this from the part 1 of this HS bio refresh? This is the basic gist of how a virus operates-- attaches to a host cell, inserts its genetic material into the host cell, that genetic material sabotages the host cell machinery and makes copies of itself, the host cell bursts to release all the new baby viral particles and it repeats.

A viral vector vaccine works like this: the genetic material of the enemy pathogen is injected into a completely different innocent looking viral envelope. Think of it like a fox in sheep's clothing. CLEVER!! Ok here's a real world example. Ready? Hold onto your hats. The Johnson and Johnson COVID-19 vaccine is a viral vector vaccine. Yep. Here's how it works. The part of the mRNA of COVID-19 that is responsible for only the spike protein is injected into .... drumroll.... an ADENOVIRUS particle. What?! Yes, way! Adenovirus is your good, old-fashioned cold virus. The common cold. Yep. So we take one of those adenovirus particles, inject a small bit of COVID-19 mRNA into the center of it (only the part of the mRNA that can produce spike proteins), and then we put that fox in sheep's clothing into a syringe and call it a vaccine. WHOA. So, now, you get an injection of this viral vector vaccine and then what happens? Bueller? Bueller? Yes, you know the answer to this.

<--- happens remember? The Adenovirus particle attaches to an unsuspecting host cell but instead of injecting adenovirus genetic material, it injects COVID-19 spike protein mRNA! The host cell is now making tiny little spike proteins (not the entire COVID-19 molecule). These tiny little spike proteins, which are harmless without the rest of the COVID-19 molecule, are now traveling around the host not doing much except now producing ANTIBODIES to COVID-19. LADIES AND GENTLEMAN, THAT IS HOW WE COME FULL CIRCLE. That is how the Johnson and Johnson COVID-19 vaccine induces immunity.

mRNA Vaccines.

But wait. You didn't talk about mRNA vaccines! Isn't that the most important one right now?? Both the Moderna and Pfizer-BioNTech COVID-19 vaccinations are mRNA vaccines. How is this different than what we've talked about above? Actually, it's not that far off. It'll all make more sense in a second. But first, let me take a minute and do a brief refresher on the basic structure of a cell, and specifically where mRNA fits in and what its purpose is.

mRNA in 5 seconds. The DNA is the molecule that contains all of the genetic material within an organism that instructs all of its cell function and growth and development. The DNA lives in the cell nucleus. Remember that from HS bio? Part of the DNA contains the instructions to make proteins. Transcription is the process where DNA is changed into RNA. RNA is then spliced into mRNA (messenger RNA). Once mRNA is formed it is then exported OUT OF THE NUCLEUS into the cytoplasm where it undergoes a process on the ribosomes called translation and a protein is formed. If you remember anything from this little paragraph, remember this: mRNA is the information used OUTSIDE of the nucleus by the ribosomes to finally make proteins. The mRNA does not go INTO the nucleus. The mRNA is formed FROM the DNA and moves OUT of the nucleus. (Any idea why I'm making such a big deal out of this point? Any guesses? RIGHT! mRNA vaccines DO NOT CHANGE A CELL'S DNA. Read that again. mRNA vaccines DO NOT CHANGE A CELL's DNA. Have you heard that completely absurd accusation? If you know even a little bit of high school biology-- as you all do now!--- you must know that mRNA does not act on DNA. DNA is the boss of all bosses. DNA tells mRNA what to do. Who is mRNA to tell DNA what to do? No way, no how. Not gonna happen. Once DNA makes mRNA, it kicks it out of the nucleus! So, I say again.... mRNA vaccines DO NOT CHANGE A CELL'S DNA).

One other point I want to review here. When the mRNA is finished with translation and the protein is made, mRNA degradation begins. That particular mRNA strand is no longer needed. mRNA strands expire. Most bacterial mRNA have a half-life of only a few minutes with bacterial mRNA half-lives varying from less than 1 minute up to 20 minutes. The average half-life of human mRNA is 10 hours. (Any idea why I'm making such a big deal about this point? Right! The mRNA vaccine does not live in your body forever changing your genetic makeup and wreaking havoc on your cell's structures. mRNA strands are destroyed once they are translated).

Ok. Back to mRNA vaccines. Now I think you have all the information to put this together and understand the Moderna and Pfizer-BioNTech COVID-19 vaccinations. These two vaccinations are mRNA vaccines. They specifically contain the mRNA strand that translates into only the spike protein of COVID-19. The mRNA is combined with a lipid nanoparticle delivery system in order to keep the mRNA stable and protected during manufacturing, storage, and injection. You know what happens from here. The mRNA is injected into the muscle cells of the arm. Once the mRNA is incorporated into the muscle cell nucleus, the mRNA uses the muscle cell's ribosomes to translate its code into the spike protein. The protein is then released into the system as if the host had been exposed to a foreign antigen/pathogen (just like how every other vaccination functions) and now the host can begin to create antibodies and stimulate the immune response. FULL CIRCLE.