News today from Harvard's Center for Virology and Vaccine Research may help solve a problem that future COVID-19 manufacturers are sure to face: how to make sure that new and potentially better vaccines actually work without doing extremely large and expensive studies.
Writing in the journal Nature, the researchers show that a certain class of antibodies in a monkey's blood predicted protection from COVID-19. If that hold true for humans, a relative simple blood test may show whether an experimental vaccine is working.
Here's the dilemma: Once a vaccine is approved, it's unethical to test it against a placebo. Approving new vaccine would require researchers to compare two vaccines against each other, instead of having a vaccine and a placebo--which would take a lot more people than the 30,000 for the initial trials.
Most researchers agree the key to solving this problem is finding something known as correlates of immunity.
"Correlates of immunity are very important because they give us insight into how vaccines work, says Dan H. Barouch, M.D., Ph.D., Principal Investigator at the Harvard vaccine center.
The idea is if you could measure something in a people's blood that would show whether a vaccine works or not, you could then focus more on whether the vaccine was safe--because researchers would already know it's likely effective.
"So it would be much more convenient for future testing of 19 vaccines to have a well-established correlate of protection," Barouch says.
This approach is already used in approving the annual flu vaccine. "There's a new influenza vaccine that's licensed every year," he says, because of genetic changes in the influenza virus.
"It would not be possible to do a large-scale clinical efficacy trial of an influenza vaccine candidate every single year," says Barouch, so regulators rely on correlates of protection.
The correlate of protection for the coronavirus vaccine, Barouch and his colleagues found, was neutralizing antibodies. These are antibodies that can prevent a virus from infecting cells. It's possible to test for the presence of these antibodies in people's blood.
It's been assumed all along that neutralizing antibodies were necessary for a vaccine to induce to be effective, but no one know for sure if neutralizing antibodies alone were enough.
The new research conducted with rhesus macaque monkeys suggests they are.
Researchers took blood from monkeys that had been infected with the coronavirus that causes COVID-19, and then recovered. That blood contained neutralizing antibodies to the coronavirus that helped the monkeys fight off the infection.
"We isolated [those antibodies], we purified them and then we transfer them alone into naïve animals," Barouch says. Naïve animals are ones who had never been sick.
They then exposed the monkeys to the coronavirus. Most showed no signs of infection, and of those receiving a higher amount of antibodies, none showed signs of infection.
The implication is if a vaccine can induce someone's immune system to make those antibodies, that alone might be sufficient to believe the vaccine will work. Some scientists have argued that vaccines must provoke other kinds of immune responses known a cellular immunity. This research suggests that might not be the case.
There are some caveats. The study was done in a small number of monkeys. Also, it's possible that human neutralizing antibodies won't work as well as the monkey neutralizing antibodies did.
Nonetheless, Barouch is bullish about the implications of this research. "This is good news for vaccines because this level of neutralizing antibodies should be readily achievable by a variety of different vaccine candidates," says Barouch.