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This article about COVID-19 vaccine research has been completely updated and can be found here. The comments section for this article has been closed.

Because the development of a potential COVID-19 vaccine is of massive interest currently, and because I have a passion for vaccine research and development, this article will a guide for vaccines involved with the coronavirus. It will be updated regularly, and I will post to social media when it is updated.

Right now, there are several COVID-19 vaccine candidates being developed by large and small pharmaceutical companies. Of course, social media will make it sound like they are all just around the corner, and they will all work.

It doesn’t work that way, so let me keep you updated with this guide to COVID-19 vaccine research and development.

All about COVID-19

Coronaviruses (there are seven that infect humans) are species of virus belonging to the subfamilyCoronavirinae in the family Coronaviridae, in the order Nidovirales. They are an RNA virus of around 26-32 thousand base pairs.

One of the myths about coronaviruses, recently stated by Donald Trump, is that it’s related to the flu. No, the influenza viruses aren’t even closely related to coronaviruses – they’re actually in two separate phyla, meaning that they are as related to one another as a human is to a lobster.

This 2019 coronavirus outbreak is known as COVID-19 and is caused by the SARS-CoV-2 virus, which is closely related to other SARS-related viruses. The virus is spread easily by small droplets from infected individuals when they breathe or cough. The time from exposure to the SARS-CoV-2 virus to onset of symptoms is generally between 2 and 14 days.

The CDC and WHO have recommended handwashing, maintaining distance from individuals who are coughing, and not touching one’s face as preventative measures. It is also recommended that individuals cover their nose and mouth with a bent elbow when coughing

The early symptoms of COVID-19 can mimic many other viral diseases – fever, cough, and shortness of breath. However, many cases progress to pneumonia and multi-organ failure. As of now, we don’t know if the disease favors particular groups. For example, smokers, individuals with chronic pulmonary disease, or seniors may be at higher risk of dangerous complications like death.

As I mentioned above, severe acute respiratory syndrome (SARS) is caused by SARS-associated coronavirus (SARS-CoV), which means that the current coronavirus outbreak is related to SARS. In addition, the a href=”https://www.cdc.gov/coronavirus/mers/” target=”_blank” rel=”noopener noreferrer”>Middle East respiratory syndrome (MERS) is caused by the Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

Coronaviruses, like the SARS-CoV-2, MERS-CoV and SARS-CoV species, infect the upper respiratory and gastrointestinal tracts of mammals and birds. Interestingly, coronaviruses may cause a substantial percentage of all common colds in humans.

The SARS coronaviruses have unique pathophysiologies because it causes more severe upper and lower respiratory tract infections.

At this point, we don’t have firm evidence for a particular non-human reservoir for the SARS-CoV-2 virus, the viruses mutation rate, or just about anything important. But we have a lot of myths.

This image depicts a Centers for Disease Control and Prevention (CDC) intern, Maureen Metcalfe, as she was using one of the agency’s transmission electron microscopes (TEM). The microscope’s screen was displaying a thin section of the variola virus, revealing some of the ultrastructural features displayed by this pathogenic organism, which is the cause of smallpox. Photo by CDC on Unsplash.

Developing a COVID-19 vaccine

I wrote previously about how a COVID-19 vaccine is developed. But it bears repeating.

An average vaccine takes anywhere from 2-5 years to develop before a clinical trial can begin. However, with the worldwide collaboration and government money, we might have a COVID-19 vaccine ready for clinical trials sooner than that.

Here are the steps in order:

Identifying methods to induce an immune response. There have been two peer-reviewed papers recently published (here and here) that may have identified vaccine targets. Generally, better vaccines are developed to target certain glycoproteins on the virus coat which are stable, that is, don’t mutate frequently. Having this kind of early research helps vaccine scientists produce a better vaccine. Pre-clinical studies. This step will help scientists understand SARS-CoV-2 characteristics and pathophysiology in humans. Since it would be unethical to do these studies in actual humans, researchers need to develop an animal model that mimics a human. Also, researchers need to determine if the vaccine is safe and triggers an adaptive immune response in that animal model. For the SARS vaccine, ferrets were used, because their physiology and immune responses are similar to humans, so it might be used for a COVID-19 vaccine. IND application. The sponsoring organization (probably a Big Pharma company) must make an Investigational New Drug (IND) application to the FDA’s Center for Biologics Evaluation and Research (CBER) to begin clinical trials. CBER reviews the IND, which will include preclinical data, and the sponsor can proceed with the clinical trial within 30 days if the FDA does not find cause to stop it from moving forward. This is the process in the USA, but it’s much the same in most developed countries. Clinical trials. Then the sponsoring organization must get Institutional Review Board (IRB) approval to proceed with clinical trials (see this article for more information about the process). The clinical studies must go through three phases like all drugs, although the process could be shortened if the data is very clear and a public need (like the coronavirus pandemic). These clinical trials will be posted to a US government website that tracks all clinical trials worldwide (and must be posted there before a drug can get US FDA approval). Final regulatory approval. After all of the preclinical and clinical is completed, the sponsoring organization must make a Biologics License Application (BLA) to CBER. Although this process is what is done in the USA, it’s similar in most other countries (and some countries accept FDA review for their own country. Manufacturing plan. During this research, regulatory agencies must review manufacturing plans for the new vaccine and any pharmaceutical company that intends to produce it must develop a cost-effective and consistent method for production.

I remain convinced that a lot of people, whether they are pro-vaccine or anti-science, think that researchers grab a handful of viruses, a little water, some mercury, an aluminum Diet Coke can, and an aborted fetus, throw it in a Waring blender, put it in a vial, and then inject them into innocent children.

In reality, this process is time-consuming, as is very difficult. Although some of these steps can be speeded up by a few months, it’s not something that can be done in a few weeks, even in an emergency.

Putting the brakes on overpromising

Even though I don’t want to sound like I’m anti-vaccine (wow, that busted my irony meter), but I want to see significant randomized, double-blinded clinical trials. I want to see it published in a peer-reviewed journal. I want to know that the candidate vaccine was vetted for both extraordinary safety and extraordinary effectiveness – as we’ve done for every single vaccine available to humans.

So important to get the details right here. NIH might be able to begin a very small, phase 1 trial in a few months — which is lightning fast — but a larger trial with lots of people won't be ready until at least next year. https://t.co/dLAzt4pCfZ — Liz Szabo (@LizSzabo) March 2, 2020

Despite what you’re reading on the internet, and what Trump is saying, we are a long way from having a vaccine ready for pivotal clinical trials that will give us an indication of safety and effectiveness.

Paul Offit, MD, who is one of the leading vaccine scientists in the world, and a leading target of the anti-vaccine movement, was interviewed by the Philadelphia Inquirer recently about a potential coronavirus vaccine:

Why is it unrealistic to expect a vaccine for coronavirus in a few months? Nobody’s ever seen this virus before. Therefore, if you’re interested in making a vaccine, you first had access to that virus only a couple months ago. That’s not long. [To make a vaccine] you first need to make a decision as to what approach you want to take. Then you have to do extensive animal model testing to make sure that the approach that you’ve taken is safe in animals, and that it induces an immune response which would likely be protective. Then you gradually do studies in people to make sure it’s safe, and then to make sure that it induces an immune response. That takes time, a lot of time, typically years. Then and only then, are you ready to put it into people to see whether or not it works in an outbreak situation.

This cannot be stressed enough – even if everything goes right, it may be years before a vaccine is widely available. I think way too many people believe that once a drug enters clinical trials, it must work and only government regulations prevent it from getting to the market quickly. In fact, around 87% of drugs that enter Phase 1 clinical trials eventually fail to get FDA approval.

As an interesting historical note about vaccine development for coronaviruses, Dr. Peter Hotez, one of the leading vaccine scientists in the USA, lead a team that was close to developing a SARS vaccine, which might have been useful for this pandemic. Unfortunately, his team did not get further funding as SARS did not proceed to a full pandemic.

COVID-19 vaccine candidates

Biological Research Institute. This Israeli research center is claiming that it has a vaccine candidate. The institute, which is a part of the Israeli Department of Defense seems to contradict their claims:

Asked about the development, the Defense Ministry said: “There has been no breakthrough in the efforts of the biological institute to find a vaccine for the coronavirus or to develop testing kits. The institute’s work is conducted according to an orderly work plan and it will take time. If and when there will be something to report, it will be done in an orderly fashion. The biological institute is a world-renowned research and development agency, which relies on experienced researchers and scientists with great knowledge and quality infrastructures. There are now more than 50 experienced scientists working at the institute on researching and developing a medical remedy for the virus.”

As you can see, except for Moderna, all of these vaccines are in very early preclinical development. And I’m concerned that I’m having a difficult time finding actual scientific data that shows us data from the preclinical studies (even for Moderna). Most of the information here comes from corporate press releases, which is near the bottom of the hierarchy of scientific evidence.

Summary

But there are several points of caution, that I need to emphasize with all of the voice I can give to this:

Entering clinical trials means nothing. That doesn’t mean we have a vaccine right around the corner. Most vaccines that enter clinical trials fail, and I have no confidence that any of these vaccine candidates have any better chance of being successful. That being said, the only thing that matters is data from pivotal, large phase 2 and 3 clinical trials. We need to know that the vaccine is safe and effective, something we do for every vaccine on the market. If we lack solid data that the vaccine is safe and effective, you can predict that the anti-vaccine forces will be out in force whining about “mandatory vaccinations,” making false claims and refusing the vaccine. This could harm the herd effect in stopping the disease. We don’t know the rate of mutation for SARS-CoV-2, which could make the vaccine ineffective. Other SARS vaccines have failed in clinical trials.

The best thing I can say a lot of companies, governments, and non-governmental entities are focused on developing a COVID-19 vaccine. This could speed up the timeline for a new vaccine, but clinical trials take time – remember each patient who receives the vaccine or placebo have to be monitored over several months to see the antibody response (or lack thereof).

Thus, we can be cautiously optimistic about a vaccine sometime in 2021. But that’s if everything goes right, and after many years in research and development, I can state with authority that everything rarely goes right.

Update 16 March 2020

As I wrote above, Moderna is starting a clinical trial at Kaiser-Permanente in Seattle, Washington. The study will only include healthy volunteers between the ages of 18 and 59 years of age.

The protocol includes three injections over a few months, and the safety and effectiveness will be monitored over 12 months. Given that this Phase 1 data may not be available for a year, I remain highly skeptical that this vaccine will be available until late 2021 if all goes well.

There seems to be an odd myth across the world that just because a vaccine enters a clinical trial, it must, therefore, be safe and effective. The anti-vaccine charlatans like Del Bigtree and Robert F Kennedy Jr, both of whom lack any credibility about vaccines, push that narrative to push fear, uncertainty, and doubt. However, the facts are that a coronavirus vaccine will not be widely available until the sponsoring company firmly establishes safety and effectiveness.

And this is why most experts on vaccines are pumping the brakes on optimism. We may not see a coronavirus vaccine for a long time.

Update 26 March 2020

Although it has nothing to do with a COVID-19 vaccine, the evidence that the anti-malarial chloroquine can treat coronavirus is laughably weak. There are no robust, repeated, well-controlled clinical trials that show that the drug will do anything for treating COVID-19. None.

Citations

Notes

As I mentioned at the top, I intend to update this article frequently as new vaccine candidates are announced along with the timelines for preclinical and clinical studies. If anyone has other candidates that I missed, leave a comment, and I’ll look into adding it.

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The Original Skeptical Raptor Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!

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