The vax method to the COVID-19 madness: Vaccine development in a pandemic

With the recent good news regarding potential SARS-CoV-2 vaccines, I thought it would be helpful to blog about the vaccine development process and how that process has evolved during the ongoing pandemic.

Let’s begin with understanding what’s happening in your immune system during an infection. My last blog on “herd immunity vs. immunization” described how the immune system creates specific antibodies that bind to the microbes causing the infection, hopefully neutralizing them. B cells, the antibody-producing immune cells, then mature to become memory cells that can “remember” the pathogen and quickly neutralize it upon the next encounter. A vaccine is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins so that your immune system will be provoked to produce antibodies as if you were exposed to the disease, but without the damage caused by the actual infection, which the vaccine is not capable of causing.

Currently, there are 200 vaccines for SARS-CoV-2 in development, 43 of which are in human trials in various phases. Here are the most common approaches to vaccine development:

1. Inactivated and Live Attenuated Vaccines – Most vaccines today incorporate an inactivated or weakened form of a virus. This technique requires growing the virus many times over; for example, the flu virus is grown in chicken eggs. It takes months to grow the number of viruses needed to make the target goal of Operation Warp Speed (300 million by January 2021).
2. DNA Vaccines – Instead of the whole virus, genetic instructions in the form of a circle of engineered DNA is delivered into the cells. The cells read the instructions of the viral gene and make a copy in a molecule called messenger RNA (mRNA). The mRNA then creates viral proteins that stimulate the immune system to make antibodies. DNA vaccines have not yet been approved for human use.
3. RNA Vaccines – This approach skips the whole process of DNA to mRNA conversion and delivers mRNA directly to the cells instructing viral protein creation. RNA vaccines have not yet been approved, but are in the clinical trial phase.
4. Viral Vector Vaccines – In this method, the virus invades the cells using another virus. In the case of the coronavirus, researchers used the adenovirus modified to have the spike protein gene. The adenovirus invades the cells and unloads the gene. With the adenovirus missing one of its own genes, the virus cannot replicate, making it harmless. Vaccines for HIV and Ebola have been created using this method and are now in efficacy trials.
5. Virus-like Particle Vaccines – These vaccines are made from pieces of viral proteins. Because they are not a true virus, they are considered safe while still triggering the immune system.
6. Recombinant Vaccines – Other cells such as yeast can be genetically engineered to carry the specific virus gene. The cells can then produce the viral proteins which are then collected and developed into a vaccine. An example of this would be the shingles vaccine.

First, research sponsors begin by selecting a production method and developing a candidate through research and selective humane testing on animals. When the U.S. Food and Drug Administration (FDA) approves, clinical trials can begin on humans. There are four phases to clinical research trials:

Phase 1

• Assesses the safety of the vaccine in a small group of volunteers
• How will this vaccine work?

Phase 2

• Assesses both safety and efficacy in a slightly larger study group.
• Is it safe and what is the right dose?

Phase 3

• Assesses efficacy in a large population of subjects against control groups.
• How effective is the vaccine?
• After a success Phase 3, regulatory approval and licensure.
• Is it ready for the world?

Phase 4

• Optional studies pharmaceutical companies may be required to perform after a vaccine is licensed to continue to monitor safety and effectiveness.
• Will it stay safe down the road?

Let’s compare the traditional vaccine development timeline to the current pandemic vaccine development timeline:

When it comes to SARS-CoV-2, what is the government doing differently from the traditional vaccine development track?

For one thing, in Phase 3, they are running much larger trials than usual. About 30,000 subjects are being tested per trial. Scientists are making strides in the vaccine development process, shortening years to months by running different processes simultaneously rather than in sequence. Large-scale production of the vaccine starts around Phase 3, whether they are approved or not, so the vaccine can be released with no ramp up time once it has been proven safe and effective and the FDA grants approval. With the help of the Department of Defense, among other federal agencies, preparation is being made for nationwide distribution. Here’s looking forward to a safe and effective SARS-CoV2 vaccine in the near future!

Precious Porter, RN, BSN, clinical data analyst at 3M Health Information Systems.

Visit the 3M HIS COVID-19 resource page.