A Covid Vaccine Q&A

A legacy article originally published on August 15, 2021 under the title “Big Covid Post #1”

What exactly do vaccines do?

Vaccines induce a part of the immune system called the adaptive immune system to produce a targeted response to a foreign body known as an antigen. The most famous actor in the adaptive immune system is the antibody which are made by an immune system cell called a B lymphocyte, or B-cell for short. But B-cells and antibodies are far from the only actors here. Another cell of the adaptive immune system is the T-cell. The T-cell also recognizes antigens via its own analog of the antibody, the T-cell receptor (TCR). Traditionally vaccines were made up of killed or weakened viruses or viral particles. When the vaccine is injected, those B-cells and T-cells whose antibodies & TCRs recognize the antigens in the vaccine will bind to those antigens. That binding results in a signal that causes those B-cells and T-cells to clone themselves, a process called clonal expansion. Most of those clones will become foot soldiers in the war against the invader. But some of those clones are given a special signal which marks them for archiving. These are the so called memory B-cells and memory T-cells. These get tucked away for later use should the same invader return. The body has no way of knowing that in the case of a vaccine, the foot soldiers are not needed — the antigens in the vaccine have been rendered harmless — it is the production of the memory cells we are after.

How do mRNA vaccines differ from traditional vaccines?

As discussed above, traditional vaccines involve directly injecting viral antigens into a host animal. Think of those antigens like some kind of Lego structure. The body produces B-cells and T-cells whose antibodies and TCRs will “snap” to that Lego structure. In an mRNA vaccine, instead of injecting the viral antigens themselves we inject the molecular instructions encoding those antigens. This is like handing out the Lego “instruction booklet” instead of the completed Lego structure. The booklet gets taken up into any cell of the body. Those cells read the booklet and follow the instructions using their own machinery to piece together the specified Lego structure brick by brick. Those cells then spit out the completed structure which then go on to induce the immune response by interacting with B-cells and T-cells.

This is the same process by which our body makes its own proteins. In the nucleus of the cell, DNA is copied to mRNA in a process called transcription. That mRNA leaves the nucleus through tiny holes and goes out into the fluid part of the cell called the cytoplasm. In the cytoplasm, the mRNA is read by something called a ribosome which pieces together the protein uniquely specified by the sequence in the mRNA. This step is called translation. Self-proteins will not cause an immune response when they interact with B-cells and T-cells because those cells have been trained to ignore self proteins during their “basic training” which occurs in the germinal centers of lymph nodes.

I always thought vaccines prevented people from getting infected and transmitting the disease. Now we are being told that vaccinated people can still get infected with Covid and spread it and should continue to wear masks. This seems fishy. Can you reconcile this?

Answering this is going to require going on a bit of a journey. There are many parts of the immune system, antibodies are just the most famous. Even among antibodies there are multiple different subtypes. The technical term for antibody is Immunoglobulin (Ig for short). Immunoglobulin subtypes are denoted by a single letter (for example IgM, IgG, IgA, IgE, etc). Each has unique functionality. Covid is a respiratory virus that enters the body through the lining of the upper respiratory tract. The antibody isotype that guards the lining of the upper respiratory tract is IgA. The Covid vaccines (and all injected vaccines) induce a strong IgG response but not much of an IgA response (none or almost none, actually). So when Covid enters the nasopharynx of a vaccinated individual, it finds the front gate unguarded and walks right in. But as soon as it tries to push any deeper into the body, it meets an army of IgG, B-cells, and T-cells. It won’t get far. This is the reason vaccinated people for the most part either suffer no symptoms or only mild symptoms limited to the upper respiratory tract and are spared “deeper” and more severe forms of Covid infection like pneumonia, encephalitis, vasculitis, etc. But, because Covid is able to get a shallow foothold in the upper respiratory tract even in vaccinated individuals, it is able to replicate there and be spewed out in droplets and aerosols that can transmit Covid to other people. Since early Covid infection in everyone starts in the upper respiratory tract regardless of vaccination status, the early course of Covid looks about the same in vaccinated and unvaccinated individuals. The viral counts go up at similar rates and to a similar degree. But after about 4 or 5 days, the nasal viral load in vaccinated people peaks and then drops precipitously while remaining elevated or continuing to rise in unvaccinated people. Vaccinated people almost always recover completely at this point while the unvaccinated remain at much higher risk for the infection moving into tissues beyond the upper respiratory tract to become a more serious infection. Since vaccinated people can still replicate virus in their upper respiratory tract for a few days early on during which time viral loads can be just as high as in the unvaccinated, masking can reduce the possibility of transmission of Covid by vaccinated people. Wearing a surgical or sufficiently dense cloth mask reduces the droplet mode of transmission (but not transmission by aerosol) thereby providing additional protection to people other than the wearer. on the other hand, a properly fitted and handled N95 mask blocks both droplet and aerosol transmission and protects both the wearer and others. Note that the requirement that it be properly fitted and handled is a stringent constraint on N95 effectiveness. For example, in a properly fitted N95, you will not be able to smell the perfume or cologne of someone else who is in the room with you or who recently passed through. If you can smell someone’s perfume in your N95, it is not properly fitted. Finally, as will be discussed in a later FAQ, the decrease in the duration of infectiousness in vaccinated people to 5–7 days rather than the 14–21 days of an unvaccinated person has an important consequence for the spread dynamics of Covid. Specifically, it has the effect of reducing the “effective R” value (in the vaccinated) below the R_naught value you have probably heard about. If that last sentence makes no sense to you, don’t worry, we’ll get to that.

I always thought that vaccination induced permanent immunity. Why am I hearing that with Covid, immunity may not be permanent?

This is a hard question to answer because there is a lot that is unknown. It is true that some vaccines and natural infections result in lifelong immunity while others produce only short-lived immunity. The archetypal vaccine examples of measles and mumps induce lifelong immunity. Despite this, permanent immunity is not a foregone conclusion and no one knows exactly why in all cases. A few things are known, however:

1. Viruses that mutate quickly change their antigens so that the body may no longer recognize them. Influenza is one example. If you are infected by influenza one year, you will make antibodies to that year’s influenza antigens. But next year’s influenza will have changed some of its antigens. Still though, next year’s flu will probably have some similarities with antigens from older flu’s. For that reason, having antibodies from prior years may attenuate the flu illness even though they may not prevent it completely. Because our immune systems have seen many flu’s we have antibodies to many different year’s flu’s. This is why most flu’s do not result in major pandemics year after year. We all have antibodies that are “partial matches”. Every once in a while, though, a major antigen shift occurs and produces a flu that is a particularly poor match for any of the antibodies that we have. Often this results when a human influenza virus happens to pick up bits of genetic material from a pig or bird influenza virus. Those cases can result in major influenza pandemics. Depending on which animal reservoir the new antigen came from — bird or pig — it is often called bird flu or swine flu.
2. Viruses that bind the upper respiratory tract don’t induce a very strong antibody response. The upper respiratory tract includes the nose, sinuses, pharynx (back of nose and back of throat), and larynx (where the vocal folds are). The lower respiratory tract consists of the trachea, bronchi, and lungs. The upper respiratory tract has a powerful innate immune system. The innate immune system is distinguished from the adaptive immune system in that the innate immune system is not targeted to particular antigens and includes barriers such as our skin, nasal membranes, oral membranes, and mucus. It also includes dynamic elements such as bones inside our nose called turbinates cause inspired air to rotate in a cyclone. This spinning inspired air causes particles carried along like pollen or smoke to “spin out” of the airstream and get stuck in the nasal mucus thereby preventing them from being inhaled deep into the lungs. The innate immune system also is made up its own types of cells. T cells and B cells belong to the adaptive immune system while macrophages and natural killer cells (NK cells) belong to the innate immune system. These cells lack the specificity of B cells and T cells and can attack and kill a wide range of infectious particles. Perhaps because of the upper respiratory tract’s powerful innate immune system, the body mounts a less intense adaptive immune response. No one really knows why.
3. In some cases (like chickenpox where immunity wanes about 50% over an average human lifetime) we may naturally be getting periodic boosters. In childhood most of us either get chickenpox or we get the vaccine. Subsequent to that first exposure and throughout our lives we are probably getting periodically re-exposed. The re-exposure “re-ups” our immune system memory keeping it robust. We are not aware of those periodic re-exposures because our immune system eliminates the virus before we get sick. Still, the re-exposure provided enough of a stimulus to boost our body’s response against it.
4. The immune system does a better job of recognizing “regular” patterns of antigens. Most viruses have a repetitive, lattice-like pattern. But some things like tetanus (which is a bacterium, Clostridium tetani) lack that regularity. We do not form a good response against C. tetani. Instead we immunize against the toxin molecule that C. tetani produces rather than to the whole organism.
5. Some sneaky viruses when they burst forth from an infected host cell will tear off a bit of that cell’s membrane, taking that membrane piece with them. They use that piece of membrane to cloak themselves. This is called a viral envelope. When the host’s immune system encounters an enveloped virus, what it sees is a bunch of its own self-molecules which it has been trained to ignore. This helps these viruses to evade the immune system somewhat. Fortunately, viruses make a number of errors in donning this molecular camouflage which allows the immune system still to recognize and dispatch these tricksters, albeit less efficiently. As an aside, viruses with envelopes are also more susceptible to regular household soaps and lower concentrations of widely available disinfectants. For example, a nonenveloped virus may require 80% alcohol to kill while an enveloped one generally requires only 40%. Coronaviruses are enveloped viruses.

Why do some viruses mutate quickly and others slowly?

Viruses consist of a core (where the genetic material is found) and a protein coat. As described above, some viruses also have an envelope. In almost all living things, the genetic material is DNA. But for viruses the genetic material can be DNA or RNA. Because DNA has a proofreading function to correct errors during copying, DNA viruses mutate very slowly. RNA viruses, lacking this proofreading function, mutate much more rapidly. Also, the larger and more complex the viral genome the slower the mutation rate. The mechanism behind this observation may be known to experts, but not to me.

Do mRNA vaccines turn my own cells into virus-producing zombies?

No. Covid’s full genome is ~30,000 base pairs long and encodes 29 distinct proteins. Pfizer’s and Moderna’s mRNA vaccines each contain fewer than 5,000 base pairs and encode only 1 protein, the so-called “spike protein”. For this reason, the vaccines cannot cause you to make whole viruses. Furthermore, unlike DNA which is stable for long periods of time, RNA is not. It degrades quickly and is gone in just 72 hours. This means that once the vaccine is injected, it will be taken up by your cells and for about 3 days be used as the template to make many copies of just that one spike protein. Your body then produces an immune response to that spike protein. Since there is no mechanism by which your cells can duplicate the mRNA and make more, you will never have more vaccine mRNA than you are originally injected with. From the moment the vaccine is injected onward, the amount of vaccine mRNA in your body is continually decreasing and reaches zero after 72 hours. After about 3 days the injected mRNA has been completely degraded and you are no longer making any more spike.