Discoveries
The Race to Develop a Vaccine for COVID-19
The novel coronavirus (COVID-19) has spread across the nation at record speed, infecting millions of Americans and forcing countless others to stay at home 24/7. The race to develop a vaccine to curb its spread has been underway since before the pandemic hit the U.S. More than 100 vaccines and over 80 pharmaceutical products are already under investigation.
"The usual lag time from vaccine development to getting an injection in your doctor's office is five to 10 years," says Moshe Arditi, MD, academic director of Pediatric Infectious Diseases and Immunology at Cedars-Sinai. "Yet, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, set an aspirational goal, charging scientists to get the job done within 12-18 months, which would be unprecedented."
We asked Dr. Arditi to explain how vaccine development works and why the rules are changing as scientists attempt to develop a vaccine for COVID-19.
"I have no doubt we'll emerge stronger from this virus than we were before. But unlike MERS, SARS and H1N1, the coronavirus pandemic will change forever the way we conduct scientific investigations in this country and around the world—and infectious disease research is going to be a top priority for decades to come."
How are vaccines usually developed?
Dr. Arditi: Vaccines are designed to mimic the immune response an individual naturally develops after exposure to infection. This teaches the immune system to recognize the pathogen, enabling the body to clear the infection the next time it is exposed.
Initially, we begin testing ideas in the lab or in laboratory animals. Then the product goes through multiple phases before it gets tested in thousands of people (see sidebar).
With COVID-19, we need to look at people who have recovered from the virus to identify the appropriate immune response and then try to replicate it. This whole process can take years, but given the scale of the current pandemic, we must streamline our efforts.
Vaccination platforms used to develop vaccines against COVID-19
Researchers are working hard to develop a safe and effective vaccine against COVID-19. To date, the most viable options include:
- mRNA-based vaccines: These vaccines rely on something called messenger RNA, or mRNA, to build an immune response. Scientists have identified the sequence for a key protein on the surface of the COVID-19 virus called spike protein. Scientists can place the instructions for making the spike protein into mRNA, and deliver it to people in the form of a vaccine. When a person gets a vaccine with that instruction molecule, their cells use it to construct the spike protein, which teaches the immune system to recognize the spike protein and make antibodies against it. Then, the body will be ready with antibodies if the person encounters the coronavirus..
- DNA-based vaccines: These vaccines are similar to mRNA-based vaccines, except that they encode the viral instructions in DNA.
- Adenovirus associated vaccines: Unlike mRNA and DNA, these vaccines use a weakened version of the adenovirus (a virus that can cause cold symptoms), taken from chimpanzees. Scientists genetically alter the adenovirus so it can't reproduce, then combine it with DNA plasmid encoding the spike protein of COVID-19. This triggers the immune system to produce antibodies that neutralize the virus.
- Live attenuated virus and inactivated virus vaccines: Two of the most traditional types of vaccines that laboratories are working on use the coronavirus itself to elicit an immune response. The vaccines either use "attenuated" virus, which is a weakened form, or "inactivated" virus, which has been killed, to induce the full spectrum of antibodies to neutralize the virus.
How do we ensure vaccines are safe?
Dr. Arditi: Among all pharmaceutical products, vaccines go through the most rigorous testing and scrutiny to ensure safety. That's because we give vaccines to healthy people to prevent them from getting sick.
We have to be extremely careful to ensure that vaccines designed to prevent disease don't pose any risk to a person's health. This is why it takes so long; vaccine safety testing is extensive and requires multiple phases that cannot be easily compressed.
Which methods of vaccination show the most promise for COVID-19?
Dr. Arditi: Right now, the most promising possibilities focus on products that trigger a natural or synthetic immune response that can successfully clear the virus. The big questions are: What are the correct immune responses that effectively and safely clear the virus? How many times do we need to give the vaccine, and which doses are required to generate such a response?
Scientists are taking a multipronged approach, trying to develop vaccines that use either DNA, RNA, adenovirus and inactivated or live attenuated versions of the virus, among others (see below).
Stages of vaccine development
- Phase I: Scientists test the vaccine in a very small group of volunteers—usually 30 or 40—to see if they develop an immune response and ensure there are no negative side effects.
- Phase II: Testing expands to hundreds of people and includes different age groups, such as children and the elderly, similar to those for whom the new vaccine is intended. The goal is to determine safety in a more diverse set of subjects.
- Phase III: Scientists extend the number of people to tens of thousands of healthy volunteers to test the vaccine's efficacy during a natural infection season to determine how many contract the disease in an area where the virus is circulating.
- Phase IV: The product goes to market, and federal agencies, including the Centers for Disease Control and Prevention and the Food and Drug Administration, continue to monitor the vaccine for safety and efficacy.
What are the greatest challenges to producing a viable vaccine?
Dr. Arditi: Even when vaccines make it past the development stages, they are notoriously difficult to produce and distribute widely. Researchers need to figure out not only which antibodies are protective against the virus during a natural immune response, but also what level of antibody is required to achieve immunity.
They also need to test the vaccine among different populations—young people, pregnant women and the elderly, and complete all safety trials. That's why vaccines typically cost more than a billion dollars to make and more than a decade to develop and distribute.
How can we streamline the process for the novel coronavirus?
Dr. Arditi: I believe that there's a tremendous need to create a sort of "Global Manhattan Project" to develop a universal vaccine as well as treatments and better diagnositics for COVID-19. So instead of individual countries working in silos, researchers across the globe would come together to speed vaccine development.
While there is no shortcut for the vaccine development timeline, some people are suggesting streamlining vaccine development—for instance, by performing "challenge trials," in which scientists vaccinate a small number of volunteers, wait until they develop antibodies, then expose them to the coronavirus in order to test the vaccine's efficacy more quickly.
Unlike anything that we have encountered, including MERS, SARS and H1N1, the coronavirus pandemic will forever change the way we conduct scientific investigations in this country and around the world—and infectious disease research is going to be a top priority for decades to come.
What should we do to protect ourselves until a vaccine is available?
Dr. Arditi: Everybody needs to follow stay-at-home orders, practice physical distancing, continue to wash their hands often and do everything they can to maintain a strong immune system: eat healthy, exercise regularly and get enough sleep.
