When Will This REALLY be Over? Part 4 of 4: Vaccines and Other Prophylactics

Welcome back for the final essay in this series about infection prevention approaches that could end the pandemic. First, I’ll share a model illustrating the continuum of COVID-19 prevention and treatment approaches. Second, I’ll review how drugs can help our immune system fight off viral invaders. Third, I’ll discuss vaccines, including their development process, technologies used, and critical questions. Finally, I’ll conclude with an updated answer to this series’ central question, “when will this really be over?”

COVID-19 Prevention and Treatment Crossroads

There is an enormous scientific effort underway to learn which prevention and treatment approaches are most effective. These studies can be categorized by where the research aims to intervene along the path of COVID-19 exposure and disease progression.

Imagine a long road beginning with a person who is unexposed to SARS-CoV-2 and ends with that person dying from COVID-19 disease. In the figure, this is the main horizontal road. Along the lane are seven exits labeled A through G. Each time the person misses a left turn, they progress one step closer to possible death. The goal of all prevention and treatment research is to learn which tactics best steer people away from disease toward the escape hatches for health, recovery, and survival.

A) Avoiding exposure to the virus

If we avoid the virus altogether, there is no risk of infection. Group A prevention measures keep the virus off our bodies’ surfaces. Examples of these strategies include wearing a mask, staying at home, not kissing, not shaking hands, social distancing, wearing gloves, and avoiding travel.

B) Keeping the virus on the outside of the body from getting inside

It is not always possible to avoid contact with the virus, regardless of how careful we are. Dormant virus on the outside of our bodies, though, is not a problem. The virus needs to get inside to infect us. Handwashing, hand sanitizing, not touching our faces, and washing laundry after we’ve been among potentially infected people are some of the ways we can keep the virus from getting inside our bodies.

C) Helping our immune system get rid of the virus inside the body before it causes infection

Sometimes we can’t stop the virus from getting inside our bodies. Someone might sneeze directly on us. Or we might inhale air containing lingering virus from another person. Perhaps we touched a contaminated door handle then ate chicken wings without washing our hands first.

Virus inside our bodies, however, does not necessarily mean we will get an infection. It will only cause infection if it attaches to a human cell, sneaks inside the cell, and begins replicating. Several things can happen to stop infection even after the virus is inside our bodies. For one, our innate immune system might realize the virus is not supposed to be there and naturally get rid of it. Drugs can also help our bodies inactivate viruses. The technical term for this is “prophylactic,” which is the medical term for preventative medicines or approaches.

The focus of this essay will be on these human prevention tactics, called group C in the figure. Vaccines and other treatments can prevent us from getting infected even after we have SARS-Cov-2 inside us. This step is critical because it is the final left turn in the land of prevention. Prophylactics are our last chance to avoid becoming infected and contagious— endangering ourselves and others.

For context, though, before returning for a deep dive into group C approaches, let’s discuss the rest of the continuum of COVID-19 disease progression and treatment intervention crossroads.

D) Learning why some infected people never feel sick

If a person becomes infected, there is a range of possible outcomes depending on how sick they become. Some lucky people are infected without symptoms. Researchers are trying to discover why this happens because it might help us find new treatments.

E) Healing at home

Most people who feel sick, though, fall into category E— they get better on their own at home. If we go to the hospital with a COVID-19 infection, we expose healthcare workers to the virus, risk catching a different infection, and become isolated from people we love. Research in this area aims to clarify when symptoms have turned critical enough to warrant hospitalization.

F) Returning home from hospitalization fully recovered

Once in the hospital, the research aims to determine which drugs and treatments promote quick recovery and avoid permanent damage. Approaches in group F include learning when it is appropriate to use a ventilator and deciding which medicines work best.

G) Surviving with permanent health effects

In the last possible left turn, the goal of group G research is to save critically ill patients from death. The term “compassionate use” covers research using riskier, unproven treatment approaches after all standard efforts fail. When critically ill COVID-19 patients recover, unfortunately, they often have permanent lasting health effects.

How Drugs Can Help Our Immune System Prevent COVID-19 Infections

Let’s talk more about the approaches I called group C in the last figure in more detail now. These are the ways we can stop a coronavirus that snuck into our bodies from causing an infection. First, I’ll explain how our immune system naturally does this. Then we’ll talk about three preventative human interventions.

You’ve probably heard that our bodies have never been exposed to this virus before. Therefore, we have no immunity against it. This is true, for one part of our immune system—the part designed to target specific unwelcome germs. The other part, our innate immune system, gives us some protection.

Think of our immune cells like security guards. Our immune system tries to keep out bad germs while letting harmless germs enter. There are two different ways that security guards and our immune system can do this.

Imagine you are a retail security guard whose job is to stop shoplifting. You have a list of known shoplifters who have been banned from your store. You already know these people are bad, so you always watch for them. This is how our adaptive immune system works. Our bodies learn and remember which germs made us sick in the past. Those who have not been infected by COVID-19 lack this type of immunity.

As a security person in a store, you also know that anyone might shoplift. You need to roam the store looking for evidence of stealing even from people who are not on your naughty list. This is how our innate immune system acts. Many of us get coronaviruses in our bodies, and our innate immune system notices it is foreign. Sometimes this works well enough to prevent COVID-19 naturally. This is why it is important to stay generally healthy to support our innate immune systems. Exercising, sleeping enough, eating healthy, and reducing stress improve overall health and our innate immune response.

Sometimes our innate immune system is not enough to prevent infection, though. Fortunately, there are other ways to prevent infection using human-made prophylactic drugs. I’ll discuss three example human interventions next.

1) Receptor binding blockers

The first step in coronavirus infection is binding to one of our cells. SARS-CoV-2 prefers to stick to a piece of our cells called an ACE-2 receptor. After viral binding, it cracks open the cell and inserts its genetic material. The genes hijack our cells, converting them into virus-making factories. Our cells produce copies of the virus that spread to nearby lung cells, and the cycle continues. Eventually, we produce so many viruses that they start escaping our bodies in droplets from our noses and mouths in search of new people to infect.

One fascinating area of prophylactic COVID-19 research is focused on blocking the virus from binding to our cells. Scientists are trying to make decoys that trick the virus into binding to them instead of our cells. This approach, if it succeeds, would be ideal because it stops the virus before it multiplies and damages lung cells.

2) Antibodies administered as a drug

Another idea being tested is giving people antibodies against coronavirus. In one method, antibodies are collected from someone who has fully recovered from COVID-19. The donor provides their serum, or plasma, to a recipient. Serum donation has shown promise for COVID-19 and is likely to work well. Unfortunately, though, we are limited by the number of people who have recovered and want to donate their serum.

Manufacturing antibodies overcomes the barrier of limited availability of human serum. Our bodies naturally produce several versions of antibodies. When they are made in a lab, however, usually only one or two types of antibodies are produced. When human-made, mass-produced antibodies are given to people, the protection is often not as robust as the naturally produced serum response.

3) Vaccines

Whereas the approach we just discussed involved directly putting antibodies into a person, the vaccine approach involves tricking our bodies to produce the antibodies itself. Vaccines work by making our bodies think we already had COVID-19 and have recovered.

Of the prophylactic approaches we discussed, vaccines get the most attention in research effort and news coverage. Some believe this approach is the best and only way we’ll end the pandemic, while others doubt we’ll develop a safe and effective vaccine for COVID-19 before it fizzles out on its own. Only time will tell whose prediction is accurate.

Next, let’s do a deeper dive into COVID-19 vaccine research. You’ll need this to be an educated consumer of the constant vaccine progress news that will fill the airways in the coming months!

COVID-19 Vaccine Research and Development

In this section, I’ll explain the vaccine development process, review the different ways vaccines are designed, and the key questions we need to ask to understand the pros and cons of COVID-19 vaccines.

Vaccine development and deployment process

Several challenging milestones must be overcome before a viable coronavirus vaccine could be widely available.

First, research in laboratories and animal models is conducted to identify technologies that might work. This is called the “preclinical” phase. Currently, there are over 100 candidates in the preclinical stage of development for a COVID-19 vaccine.

If results from preclinical research look promising, the drug might begin human trials of which there are three phases. In phase 1, prototypes are given to a small group of people to determine if they are safe. If no one has an adverse reaction in phase 1, then the candidate may progress to phase 2. In this phase, researchers prove the vaccine causes the participants to make antibodies that inactivate the coronavirus. In the final and third phase, higher numbers of people are enrolled, and the dosage is determined (as well as additional evidence of safety). In the US, the FDA will approve a vaccine only if it passes all the tests in phases 1, 2, and 3. There are several vaccines currently in phases 1 and 2 for COIVD-19, but none have made it to phase 3 yet.

There will likely be several news articles touting the progress of these various vaccines in development. Until one announces that they have completed phase 3 and received FDA approval, I recommend ignoring the hype (which can sometimes be fueled by the desire of for-profit companies to drive stock sales). This is like a horse race; the ones who start in the lead aren’t always the ones that finish the race.

Historically vaccines take years (or decades) to achieve FDA approval. Some predictions on the timing for the development of a COVID-19 vaccine today, however, are optimistically based on an expectation that every study will work out perfectly the first time. The urgency of the COVID-19 crisis is accelerating timelines, but don’t be surprised if it takes longer than some guesses you hear today to get a COVID-19 vaccine.

It is also possible that we will never have a COVID-19 vaccine. We aren’t always able to develop an effective vaccine for all pathogens. For example, despite decades of effort, there is still no vaccine for HIV. Each type of virus has a unique way it interacts with our immune system. Therefore, how to make an effective vaccine is different for different viruses, and we still have a lot to learn about the novel coronavirus.

Even after a vaccine is approved, it needs to be scaled up for manufacturing. Then the vaccine must be shipped and given to people all over the world. Unless people globally get it, it won’t fundamentally make the virus stop spreading. All of this is going to take time.

Perhaps several vaccines will be developed. It is also possible, though, that no one will figure out how to make a safe and effective vaccine against COVID-19. Only time will tell. If the development of a vaccine ends the pandemic, it is going to require patience while we wait for scientific studies, manufacturing, and distribution.

Types of vaccines

Numerous technological approaches are being used to create a coronavirus vaccine, each with different advantages and disadvantages. In the figure, I bucket vaccine technologies into three categories: 1) whole coronavirus, 2) Frankenvirus, or 3) pieces of coronavirus.

The idea behind using a whole coronavirus is that it closely mimics what the real coronavirus does. In this approach, the SARS-CoV-2 virus is modified to be less harmful. This is often called a weakened or attenuated virus. Our bodies react as they would to the COVID-19-causing virus and make antibodies against it. Polio and measles vaccines work this way. We have the longest history of experience using this approach, and it generally creates a strong and lasting immune response, although it can be difficult to manufacture these vaccines.

Some researchers are trying to make weaker, but still active, versions of the virus. Another approach is to take the actual target virus and inactivate it (with heat or a chemical) and then give people the dead virus. Others take out the guts of the virus, its genetic material, so that it is still active and can get into our body and our cells, but then it won’t cause infection because it is missing the directions to make copies of itself.

The Frankenvirus approach takes parts of the coronavirus and combines it with a different type of virus. Depending on how the combination is made, the resulting mixed virus can sometimes retain the ability to replicate inside our body which amplifies the number of antibodies we make against it. There has been a lot of research in this area, but it isn’t used in vaccines on the market yet.

In the third approach, researchers are testing different parts of the coronavirus and seeing if the pieces are enough to elicit an immune response. Protein pieces of the virus that bind to our cells in our infection are a promising approach because we have lots of experience making vaccines this way. This is how current influenza and Hepatitis B vaccines work. The use of genetic directions as a vaccine is a new approach. There are no vaccines on the market today using this technological approach. Researchers are testing to see if giving people RNA or DNA genetic programming will cause our cells to make parts of the coronavirus that our immune system would then create antibodies against.

Key questions to ask about any vaccine

This coronavirus virus is new, so we don’t know what we don’t know about its vaccine development. Several vital questions must be answered before considering any solution a success. If there comes a day where we get to decide if we will get ourselves or our family members immunized against COVID-19, look for the answers to these questions:

1) How well does the vaccine protect me? If I get this vaccine, what is the chance I could still get infected?

2) How long does the protection last? Will I need a booster shot later?

3) What side effects were noticed in what percentage of the study participants? What is the length of time after getting the vaccine that the study looked for possible long-term safety concerns?

4) Is it safe for everyone to get? Has it been tested on people with my specific health conditions?

5) How well do we understand how the vaccine works? Is this based on a tried and true vaccine platform that we have years of experience with, or is this a new-to-the-world approach?

6) Can this vaccine contribute to resistance? Is it based on a technology that uses only one part of the virus or multiple parts? (Generally, it is better to have multiple so that the virus doesn’t mutate around the one piece you are using in your vaccine.)

When will this REALLY be over? My updated opinion

Today, if I answer the answer question, “When will this really be over?” I add a fourth approach, treatment. Also, of the four strategies, I now have two favorites. Only testing and tracing (“hunt and catch”), combined with treatment, can help us immediately. Herd immunity and vaccine deployment will take time, possibly too much time. The virus might fizzle out or change before these strategies can help us.

A month ago, I didn’t see treatment research as a key approach to ending the pandemic because prevention seemed more important than treating it. The possibility of treatments that are so effective it makes getting sick with COVID-19 no big deal anymore is a viable way to end the fear. When the fear is gone, it will really be over. Plus, treatment research studies don’t take long, and we are getting results fast. The time to develop superior treatments is less than to create preventative approaches. Therefore, I add treatment, “the heal” approach, as a fourth answer.

I am less excited about the prospect of the vaccine approach to ending the pandemic because I worry about the quality of the result if we rush its development. It’s valuable research, and we should work fast to find a solution, but it cannot be at the expense of rigorous solid clinical research. For example, typically, vaccines are not tested in humans if they have not yet been verified to be effective in animal models first. Some COVID-19 vaccine candidates may skip that step. Some predictions say we may have a vaccine available by year-end. If that happens, how would it give us enough time to verify with clinical trials that participants will not develop side effects that might not show up until a year or two later?

Herd immunity sounded quite possible a month ago. However, after seeing the pace that the virus has been moving, it looks like it might take too long for it to spread to a majority of humans to give us herd immunity anytime soon. Herd immunity is sounding more and more like a long-shot possibility. The virus might mutate to a new form before we ever get to global herd immunity status for SARS-CoV-2.

Maybe I am unreasonably pessimistic about the potential for the “wait it out” herd immunity or the “armor and shields” prophylactic approaches to end this pandemic. I hope I am. Regardless, though, increasing testing and tracing and healing those who are sick with improved treatments helps us sooner.

My updated opinion is that “2 out 4 ain’t bad,” and my money is on testing/tracing and treatments as the most likely indicators of when this is all really over.

I hope this essay helped explain the armor and shields approach to ending the pandemic by developing an effective vaccine or other prophylactic.

Until next time, stay well,

COVID Carrie

Where to go for more information

● WHO sites COVID-NMA (Network Meta Analysis)

o https://www.covid-nma.com/dataviz/

o https://covid-nma.com/networks/

● WHO COVID-19 vaccine research https://www.who.int/who-documents-detail/draft-landscape-of-covid-19-candidate-vaccines

● NIH clinical trials summarized https://clinicaltrials.gov/ct2/results?cond=COVID-19

● Nature article, an overview of types of COVID-19 vaccines in development https://media.nature.com/original/magazine-assets/d41586-020-01221-y/d41586-020-01221-y.pdf