History raises safety concerns
However, Ledley said, “The idea of doing it in 6 months is largely unrealistic.”
He says 18 months is more realistic, primarily because of the sheer number of people that would have to be enrolled in a phase 3 study to truly test whether the endpoints are being met.
Vaccines are given to healthy volunteers. If safety signals arise, they may not be apparent until massive numbers of people are tested in phase 3.
“You’re never going to see the rates cut to 0%, but to see the difference between 10 people getting sick and seven people getting sick, takes very, very large numbers,” Ledley said. “There’s no way that can be done in 6 months. You’re talking about tens of thousands of people enrolled.”
He notes at this point it’s unclear what the endpoints will be and what the safety thresholds will be after consideration of risks and benefit.
Another big question for Ledley: “We don’t know what type of immunity we need to protect us against the virus. Do you just need the antibodies in your blood or do you need cells that are primed to attack the virus? Is it more of a chemical clearance or do the cells need to physically go in and digest the virus?”
History also points to the need for rigorous safety precautions that scientists fear could be compromised as trial phases overlap and processes are run in parallel instead of one step at a time.
An early batch of the Salk vaccine for polio in 1955, for example, turned out to be contaminated and caused paralysis in some children and 10 deaths, he points out.
CEPI’s Lurie adds that early candidates for another coronavirus, severe acute respiratory syndrome (SARS), “caused a reaction in the lungs that was very dangerous” before development was halted.
She also pointed to previous findings that a vaccine for dengue fever could worsen the disease in some people through a phenomenon called antibody-dependent enhancement.
Lurie and colleagues write in their paper that “it’s critical that vaccines also be developed using the tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
Live attenuated vaccine
Raul Andino, PhD, a virologist at the University of California San Francisco, is among the scientists working with a tried-and-true method — a live attenuated vaccine — and he told Medscape Medical News he’s predicting it will take 2 years to develop.
He said it is cheaper to produce because scientists just have to learn how to grow the virus. Because the technology is already proven, a live attenuated vaccine could be rapidly produced on a worldwide scale.
The hope is also that a live attenuated vaccine would be given once in a lifetime and therefore be more affordable, especially in poorer countries.
“While a Moderna vaccine might be good for Europe and the United States,” he said, “It’s not going to be good for Africa, India, Brazil.”
Andino said, “I would bet money” that the front-runner vaccines so far will not be one-time vaccines.
He points out that most of the vaccine candidates are trying to protect people from disease. While there’s nothing wrong with that, he said, “In my opinion that is the lower-hanging fruit.”
“In my mind we need something that interrupts the chain of transmission and induces protection,” Andino said, important for developing herd immunity.
The reason this type of approach takes longer is because you are introducing a weakened form of the virus to the body and you have to make sure it doesn’t cause disease, not just in a small test population, but in populations who may be more susceptible to the disease, Andino said.