With coronavirus antibodies fading fast, vaccine hopes fade, too - SFChronicle.com

Disturbing new revelations that permanent immunity to the coronavirus may not be possible have jeopardized vaccine development and reinforced a decision by scientists at UCSF and affiliated laboratories to focus exclusively on treatments.

Several recent studies conducted around the world indicate that the human body does not retain the antibodies that build up during infections, meaning there may be no lasting immunity to COVID-19 after people recover.

Strong antibodies are also crucial in the development of vaccines. So molecular biologists fear the only way left to control the disease may be to treat the symptoms after people are infected to prevent the most debilitating effects, including inflammation, blood clots and death.

“I just don’t see a vaccine coming anytime soon,” said Nevan Krogan, a molecular biologist and director of UCSF’s Quantitative Biosciences Institute, which works in partnership with 100 research laboratories. “People do have antibodies, but the antibodies are waning quickly.” And if antibodies diminish, “then there is a good chance the immunity from a vaccine would wane too.”

The latest bad news came from scientists at King’s College of London, whose study of 90 COVID-19 patients in the United Kingdom found antibody levels peaked three weeks after the onset of symptoms and then dramatically declined.

Potent antibodies were found in 60% of the patients, according to the study, but only 17% retained the same potency three months later. In some cases, the antibodies disappeared completely, said the study which was published as a preprint Saturday, meaning it has not yet been peer-reviewed.

The report is the latest in a growing chain of evidence that immunity to COVID-19 is short-lived.

A Chinese study published June 18 in the journal Nature Medicine also showed coronavirus antibodies taking a nosedive. The study of 74 patients, conducted by Chongqing Medical University, a branch of the Chinese Center for Disease Control and Prevention, showed that more than 90% exhibited sharp declines in the number of antibodies within two to three months after infection.

There is still hope that the remaining antibodies will bestow some immunity, but infectious disease specialists around the world were surprised and discouraged by the rapid reduction observed in the studies. If the numbers continue dropping after three months, it could mean people will be susceptible to infection by the coronavirus year after year.

So far, though, there have been only scattered reports of reinfection and no comprehensive studies have verified that it can happen. Experts say the disease hasn’t been around long enough to determine the likelihood of contracting the disease more than once. But other kinds of coronaviruses, like those that cause the common cold, offer clues.

Studies of four seasonal coronaviruses that cause colds show that although people develop antibodies, the immune response declines over time and people become susceptible again. Scientists suspect that the severity of cold symptoms is reduced by previous infections.

“Waning antibodies affect vaccine development,” said Shannon Bennett, the chief of science at San Francisco’s California Academy of Sciences. “Where natural immunity doesn’t really develop or last, then vaccine programs are not likely to be easily successful or achievable.”

Nobody knows yet whether infections by other coronaviruses will help people’s bodies resist COVID-19.

“Our understanding of protective immunity engendered by this virus and how it interacts with past immunity to other coronaviruses is still evolving,”Bennett said. “People should not presume they have immunity.”

The recent findings are particularly disappointing because of the promising discovery this spring of “neutralizing antibodies,” the kind that attack the virus’ crown-like spikes and prevent them from hijacking human cells.

Epidemiologists found these neutralizing antibodies in less than 5% of COVID-19 patients and were hoping to isolate and use them to inoculate others, a precursor to a full vaccine. Unfortunately, the recent studies show that the super-strength antibodies also fade away.

The Chinese study found an 11.7% decline in neutralizing antibodies in symptomatic coronavirus patients and an 8.3% drop in asymptomatic individuals over the three months.

“Those are the ones you want, but they just aren’t sticking around,” said Krogan, who is also an investigator with the Gladstone Institutes, a biomedical research lab in San Francisco. “They just aren’t staying long enough in our bodies to prevent reinfection. If this is only lasting six weeks or three weeks, that’s not good.”

Even if a vaccine were produced, infectious disease specialists say it could take years before the entire population was inoculated. If the vaccine wore off over time, periodic boosters would be needed, as with influenza shots.

All of which emphasizes the need for effective treatments.

Krogan’s Quantitative Biosciences Institute, created four years ago, has been scouring the genome of SARS-CoV-2 — the specific coronavirus that causes COVID-19 — and testing in petri dishes how viral proteins interact with human cells.

The idea, said Danielle Swaney, a researcher for the QBI Coronavirus Research Group, comprised of at least 40 laboratories affiliated with UCSF, is to find ways to fight the disease once it is in the body.

“Our whole approach is to find what is the virus hijacking and what drugs can be developed to reverse that hijacking,” said Swaney, an assistant professor of cellular and molecular pharmacology at UCSF. “Basically, we try to take away what the virus relies on for survival so it can’t rely on it anymore.”

One possible target for intervention is a receptor embedded in the membrane of human cells called SigmaR1, which Swaney said the coronavirus interacts with. The SigmaR1 gene plays an important role in the functioning of tissues associated with the endocrine, immune and nervous systems.

“What we found is that if we use drugs that reduce the level of SigmaR1 in human cells, the virus cannot replicate in those human cells,” Swaney said, adding that many other potentially influential receptors are being studied.

One drug that targets SigmaR1 is hydroxychloroquine, which Swaney said is problematic because it can cause heart problems. In June, the Food and Drug Administration withdrew emergency use authorizations for hydroxychloroquine, which had been touted by President Trump despite the concerns.

The trick, Krogan said, will be to find several drugs that work against the virus and create a kind of cocktail, like the combination of treatments HIV-AIDS patients use to control infection. Researchers are currently testing drugs in hamsters and mice, and will soon be doing trials in monkeys, Krogan said. He said he hopes to develop such a cocktail by the end of the year.

It will be difficult, he admitted, because people infected with COVID-19 display so many different symptoms, some lingering long after the virus has gone.

People have reported vision problems, confusion and memory issues. Cases of chronic fatigue, heart problems, lung damage, blood clotting and neurological symptoms like dizziness and confusion have been documented in numerous patients long after the initial symptoms of COVID-19 have gone away.

Epidemiologists believe the most severe cases are the result of an overactive human immune system response. That’s what they think causes an inflammatory reaction similar to Kawasaki disease that has recently been affecting children exposed to the coronavirus, according to the Centers for Disease Control and Prevention.

Doctors at UCSF’s Benioff Children’s Hospital have recently seen dozens of children with reddish-purple lesions on the feet and hands known as acral perniosis. The rashes all appeared weeks or months after exposure to adults with flu-like symptoms, leading researchers to believe it is an after-the-fact inflammatory reaction to COVID-19.

“I’ve never seen a virus get its fingers in so many biological processes all at once,” Krogan said. “It’s a very fascinating, horrifying, complicated virus.”

The situation is not hopeless, Bennett said, because the human immune system uses both B cells, which produce antibodies, and T cells, which drive the immune response, to fight off viruses. It may be that a T cell response does not require as many antibodies to be effective, she said.

And some vaccines have shown promise, including one being produced by Massachusetts biotechnology company Moderna Inc. The Moderna vaccine provoked production of neutralizing antibodies in all 45 healthy volunteers tested during a preliminary study released Tuesday. The study did not include a comprehensive measurement of longevity, but researchers observed antibody activity for 43 days after a second injection.

Whatever happens, epidemiologists hope the recent reports about antibody viability put to rest the concept embraced by many young people of herd immunity, where the disease can’t find any more victims because so many people have survived infections and must be immune.

“This attitude that if I go out there and just get exposed — get it over with — then I’ll be immune is a dangerous presumption,” Bennett said. Now more than ever.