But Chinese researchers cracked the virus’ genetic code within weeks of its emergence late last year, and two vaccine candidates are already in early human trials — one in China and the other in the United States.

What’s the hold up?

Essentially, you can speed up the vaccine development process to respond to a pandemic, but you don’t want to speed it up so much that you allow a bad vaccine to enter the market, explained Dr. Greg Poland, director of the Mayo Clinic’s Vaccine Research Group.

“The process of developing, testing and licensing a vaccine for widespread population use is designed to be slow, deliberative, peer-reviewed, reflective, evidence-based, so that we don’t make mistakes,” Poland said.

Going too fast could lead to a vaccine that’s not effective or, worse, can cause serious health problems, Poland said.

Typically, clinical trials take 10 to 15 years and a billion dollars to complete, Poland said.

Vaccine trials come in three phases, said Dr. Wilbur Chen, an adult infectious disease expert at the University of Maryland’s Center for Vaccine Development and Global Health:

Phase I trials test whether the vaccine is safe, and usually last about six months.
Phase II trials examine how well the vaccine works in creating an immune response within volunteers, and last up to a year.
Phase III trials track the effectiveness of the vaccine in preventing infection in people who are being exposed to the pathogen. This phase could take three years or more, and depends on the virus remaining active long enough for participants to be exposed to it.
The U.S. vaccine candidate now in clinical trials was developed at record speed by scientists at the U.S. National Institute of Allergy and Infectious Diseases (NIAID) and the biotech company Moderna.

“This was very dramatic that we were able to have the first COVID-19 vaccine into clinical trials within just a couple of months,” Chen noted.

Researchers combined the virus’ genetic code with existing processes to create the vaccine candidate, said Dr. Kathleen Neuzil, director of the University of Maryland’s Center for Vaccine Development and Global Health, in Baltimore.

“The reason we were able to get into trials so quickly is because this vaccine was modeled on other vaccines for influenza and Zika, using the same manufacturing process and the same technology, but just substituting the genetic code for this SARS-COV2 virus,” Neuzil said.

This trial has enlisted 45 healthy adults in Seattle, who are being tracked for about six weeks.

The COVID-19 virus infects lung cells using “spike” proteins that line the outside of the virus. These spikes bump into receptors on the lung cells, tricking the cells into letting the virus enter and infect them.

The NIAID/Moderna vaccine aims to teach the immune system to recognize these spike proteins and destroy the virus.

The U.S. Food and Drug Administration has indicated that it is willing to speed up the regulatory process by allowing clinical trial phases to be combined.

For example, phase I and II trials could be combined by tracking both safety and immune response. Phase II trial participants could be followed into phase III, and tracked to see if the vaccine prevents community infection.

“We know we are in the middle of a pandemic right now, so we are very carefully following safety, but we really can’t forget we’re now at about the million mark for people infected with COVID-19,” Neuzil said.

But Poland warned there are potential pitfalls that need to be considered in rushing a vaccine to market.

For example, the vaccine might not provide lasting immunity, either because people’s immunity wanes quickly or because the virus mutates to get around it.

There already are concerns regarding the ability of people to remain immune to coronaviruses. People typically lose their immunity to coronavirus strains that cause the common cold within a year, Chen said.

Poland also is concerned about the focus of the NIAID/Moderna vaccine and other similar candidates on the “spike” or “S” protein alone.

“That’s one area where there’s been at least one identified mutation,” Poland said of the coronavirus spike protein. “You put a mutational pressure on an RNA virus and, no surprise, the virus mutates and changes.”

By comparison, flu vaccines include antigens related to two separate proteins on the influenza virus, to limit the virus’ ability to mutate away from a person’s established immunity, Poland explained.

Another concern is the potential for unintended safety consequences related to the vaccine.

“Something rushed out too fast that would have some significant side effect later would set back vaccine acceptance in an already vaccine-skeptical culture for decades,” Poland said.

Neuzil noted that “when we have seen safety signals with vaccines, they ordinarily occur soon after you give the vaccine.”

However, vaccine candidates earlier developed for the coronaviruses behind SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) have raised concerns about creating lung disease on their own, according to a recent editorial in the New England Journal of Medicine.

The SARS vaccine candidates tended to cause “antibody-enhanced disease” in animal testing, a condition in which a creature that’s received a vaccine not only gets infected by the target virus but also suffers worse symptoms than if they’d never been inoculated, Poland explained.

“It protected them from the virus, at the cost of antibody-enhanced disease. These animals developed an unusual immunopathological picture in their lungs and livers. The vaccines never progressed past that,” Poland said.

Similar antibody-enhanced disease reactions also occurred in the 1960s with an inactivated measles vaccine and in 2018 with a vaccine for dengue, Poland said.

Poland foresees a potential future in which a COVID-19 vaccine is rushed out but proves ineffective in preventing infection, possibly because the virus has mutated around the vaccine. “A second strain develops next year that, when it infects people who have been immunized, they are not protected because of the false immunity they have or develop antibody-enhanced disease,” he said.

There are as many as 40 vaccine candidates for COVID-19 in various stages of development, Poland said.

A second U.S. company, Inovio Pharmaceuticals, announced Monday that it is beginning phase I clinical trials in 40 healthy volunteers in Philadelphia and Kansas City, Mo. This vaccine uses a section of the virus’ genetic code packaged inside a piece of synthetic DNA.

Having many vaccine candidates will help in the process of speeding a successful vaccine to the public, Neuzil said.

“You can’t count on a single vaccine,” Neuzil said. “We want a lot of shots on goal right now, hoping that we’ll score with at least one
Dr Ajay Gambhir
Www. Vaccineindia.org