Monkeys, ferrets offer needed clues in COVID-19 vaccine race

global race for a COVID-19 vaccine boils down to some critical questions: How much must shots rev up someone’s immune system to really work? And could revving it wrong way cause harm?

Even as companies recruit tens of thousands of people for larger vaccine studies this summer, behind scenes scientists still are testing ferrets, monkeys and or animals in hopes of clues to those basic questions — steps that in a pre-pandemic era would have been finished first.

“We are in essence doing a great experiment,” said Ralph Baric, a coronavirus expert at University of rth Carolina, Chapel Hill, whose lab is testing several vaccine candidates in animals.

speed-up is necessary to try to stop a virus that has triggered a pandemic, killing more than 360,000 worldwide and shuttering ecomies. But “re’s question re is more risk in current strategy than what has ever been done before," Baric said.

animal testing lets scientists see how body reacts to vaccines in ways studies in people never can, said Kate Broderick, research chief at Ivio Pharmaceuticals.

With animals, “we’re able to perform autopsies and look specifically at ir lung tissue and get a really deep dive in looking at how ir lungs have reacted,” Broderick said.

She’s awaiting results from mice, ferrets and monkeys that are being exposed to coronavirus after receiving Ivio’s vaccine. Since species perfectly mimics human infection, testing a trio broens look at safety.

And re's some good news on safety front as first animal data from various research teams starts to trickle out. So far, re are signs of a worrisome side effect called disease enhancement, which Dr. Anthony Fauci of U.S. National Institutes of Health calls reassuring.

Enhancement is just what name implies: Very rarely, a vaccine doesn’t stimulate immune system in quite right way, producing antibodies that t only can’t fully block infection but that make any resulting disease worse.

That first happened in 1960s with failure of a vaccine for respiratory syncytial virus, RSV, an infection dangerous to young children. More recently, it has complicated efforts at vaccines against mosquito-spre dengue fever.

And some attempted vaccines for SARS, a cousin of COVID-19, seemed to cause enhancement in animal testing.

Fast forward to pandemic. Three recently reported studies in monkeys tested different COVID-19 vaccine approaches, including shots me by Oxford University and China’s Sivac. studies were small, but ne of monkeys showed evidence of immune-enhanced disease when scientists later dripped coronavirus directly into animals’ ses or windpipes.

Some of best evidence so far that a vaccine might work also comes from those monkey studies. Oxford and Sivac created very different s of COVID-19 vaccines, and in separate studies, each team recently reported that vaccinated monkeys were protected from pneumonia while monkeys given a dummy shot got sick.

But protection against severe disease is just a first step. Could a vaccine also stop virus’s spre? Oxford study raises some doubt.

Those researchers found as much virus lingering in vaccinated monkeys’ ses as in unvaccinated. Even though experiment exposed moneys to high levels of coronavirus, it raised troubling questions.

of vaccine -- how it targets “spike” protein that coats coronavirus -- may make a difference. Researchers at Beth Israel Deaconess Medical Center in Boston designed six different vaccine protos. Some only partially protected monkeys -- but one fully protected eight monkeys from any sign of virus, said Dr. Dan Barouch, who is working with Johnson & Johnson on yet ar COVID-19 vaccine candidate.

In monkeys, new coronavirus lodges in lungs but seldom makes m super sick. Ferrets — preferred animal for flu vaccine development — may help tell if potential COVID-19 vaccines might stop viral spre.

“Ferrets develop a fever. y also cough and sneeze,” infecting each or much like people do, said vaccine researcher Alyson Kelvin of Cana’s Dalhousie University.

And while COVID-19 is a huge risk to elderly, vaccines often don't rev up an older person's immune system as well as a younger person's. So Kelvin also is studying older ferrets.

Some vaccine makers are reporting promising immune reactions in first people given experimental shots, including production of “neutralizing” antibodies, a kind that latches onto virus and blocks it from infecting cells. But re's a hitch.

Said Ivio's Broderick: "Let me be honest. We’re still t clear at all on what those correlates of protection are” — meaning what mix of immune reactions, and how much, are needed.

Some clues come from blood of COVID-19 survivors, although "re’s a huge variation” in immune reactions between severely and mildly ill, Broderick ded.

Still, if vaccinated animals that produce same neutralizing antibody levels as certain COVID-19 survivors are protected — and people given test doses likewise produce same amount — “that is great comfort that your vaccine approach actually may work," said Kathrin Jansen, he of Pfizer Inc.'s vaccine research.

But ultimately real proof won't come before huge studies of wher vaccinated people get sick less often than unvaccinated.