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Coronavirus vaccines: What looks promising and who will be the first to get one?

Imagine the day when we can turn back the clock — and rediscover a life of random hugs, music festivals, busy streets, crowded campuses and a powerful economy.

This past week’s vaccine news gives us reason to hope. Scientists are increasingly optimistic that COVID-19 will someday join the ranks of smallpox, yellow fever, polio, mumps, measles and other near-vanquished diseases.

What will it take to get there? The challenges — in science, manufacturing, distribution and citizen participation — are formidable. Vaccines, alone, don’t save people; vaccinations do. To make this nightmare truly go away, forever, we need to inoculate nearly 330 million Americans and, ultimately, all 7.6 billion people on the planet.

“This is an unprecedented time in the history of vaccines,” said Bali Pulendran, professor of pathology and of microbiology and immunology at Stanford University. “There is no textbook solution.”

There’s a lot that can go wrong. The early vaccines are unlikely to provide full protection, so many of us may continue to be at risk. Because of limited supplies, there will be a phased rollout; not everyone who needs one will get one. Distrustful, some people may refuse to take them. And who’s in charge of our critical allocation decisions? There’s confusion – worrisome news, given the bungled distribution of tests, protective equipment and remdesivir, one the most-coveted COVID-19 drugs.

Despite all that, experts are beginning to chart a path to the post-coronavirus world. Here are their insights.

What was the big takeaway this past week?

The latest data on so-called “vaccine candidates” from the four top companies – Moderna, AstraZeneca/Oxford, CanSino and Pfizer – show that, so far, their products are safe. Johnson & Johnson and Merck candidates also look promising, but they’re a little further behind.

We also learned a little bit about the kind of immunity they trigger.

That’s just the start. A total of 23 vaccines have entered human trials and another 100 or so are still being designed.

Scientists at Oxford University say their experimental coronavirus vaccine has been shown in an early trial to prompt a protective immune response in hundreds of people who got the shot. In research published July 20  in the journal Lancet, scientists said that they found their experimental COVID-19 vaccine produced a dual immune response in people aged 18 to 55. (John Cairns, University of Oxford via AP)

So far, which one is best?

It’s hard to tell. The best vaccine is the one that produces the most vigorous and longest-lasting immune response. But here’s the challenge: Currently, trials aren’t measuring this response in an identical way. While we can get a rough sense of how they’re doing, we can’t make strict comparisons, said Pulendran. Efforts are now underway to standardize things.

“I think we’ll have a multi-way tie,” said Dr. Joel Ernst, chief of UCSF’s Division of Experimental Medicine – Viral Immunity and Vaccines. Over the next year or so, he said, we’ll likely see multiple vaccines that are safe, affordable and can be mass-produced. “But there is not enough data to pick a winning horse yet. … I don’t think we’re going to know that for quite a while.”

What still needs to happen?

We need data that show they actually protect people from infection. Those studies are starting now. The closest trial is located in the Sacramento offices of Benchmark Research.

Sometime this fall and winter, we’ll start to get research data about efficacy – that is, what fraction of people are protected by the vaccine, as compared to a control group. AstraZeneca says it might have something as soon as September. Moderna and Pfizer are both aiming for the end of the year. Johnson & Johnson promises early 2021; Merck, sometime in 2021 at the earliest. The timeline for CanSino, which is made in China, is less certain.

In anticipation of a successful product, these companies are already designing manufacturing plants.

Why do we need more than one vaccine?

We’ll benefit from several vaccines, said Pulendran, because no single company could meet demand. In addition, the vaccines may differ, working better in some people than others.

“If we’ve got three acceptable vaccines, we’ll get the vaccine to more people,” said Ernst. “Maybe not everybody will get the best vaccine for somebody in their demographic. But assuming they’re equally safe and differ in efficacy only a modest amount, you’re better off being vaccinated than having no vaccine at all.”

In this April 1955 file photo, first- and second-graders at St. Vibiana’s school are inoculated against polio with the Salk vaccine in Los Angeles. The polio vaccine developed by Dr. Jonas Salk and his colleagues at The University of Pittsburgh was approved for use in the United States in 1955.  (AP Photo, File)

Why first isn’t always best

Remember the Salk vs.Sabin polio vaccine debate? We started with Salk’s version, then shifted to Sabin’s. Now, with more information, we’re back to Salk’s.

Imagine that our first vaccine is only 50% effective. (The U.S. Food and Drug Administration, in an apparent effort to encourage vaccine companies, says that’s good enough for licensing, for now.) That will still leave some people, such as the elderly and those with high-risk medical conditions, perilously exposed.

If we’re lucky, vaccines will get better over time.

“It may not be the ultimate vaccine, but it’s the first iteration that can be improved upon,” said Pulendran.

“50% effective” sounds like more mask-wearing. Why can’t we do better?

Here’s the challenge: The best vaccines trigger a robust response by both arms of the immune system — antibodies and T-cells — and, unfortunately, we don’t yet have the design chops to do that.

The perfect COVID-19 vaccine would be such a good match for the virus’s “spike protein” that it would unleash a powerful first line of defense in the antibodies that latch onto the virus and block its entry into cells. It would also induce a strong second defense, through cell-killing T lymphocytes, in case the virus slips through the antibody barricade.

So far, our top candidates are prompting an antibody response, but we don’t yet know if that’s powerful enough to be protective. Two also show modest T-lymphocyte activity.

To help, scientists are working on so-called “adjuvants” — agents that, when added to a vaccine, can strengthen its power and durability. Scientists also just announced a synthetic “spike protein” that will improve vaccine design.

We ultimately may need to settle for second best: A vaccine that doesn’t always prevent infection but reduces transmission, disease and death. That’s helpful. But it’s not enough to stop the pandemic.

Samples from coronavirus vaccine trials are handled inside the Oxford Vaccine Group laboratory in Oxford, England Thursday June 25, 2020. (John Cairns, University of Oxford via AP)

Will we need more than one injection?

Probably. It’s a rare vaccine, like measles, that provides lifelong immunity.  Most of the rest, such as tetanus, diphtheria and pertussis, fade over time. Even the best flu vaccine might not get you through the winter.

Early data from at least two vaccines shows that antibody levels drop over time, suggesting the need for so-called “boosters” – weeks, months or years later – to retrigger the immune system.

If so, that greatly complicates our control of the virus. History shows people neglect to follow up.

Who’s first in line?

If you’re an average healthy adult, you’ll likely be last in line. Health care workers and people at high medical risk would likely be first, Dr. Francis Collins, director of the National Institutes of Health, said Friday.

But there are other considerations. The military, students, underrepresented minorities, “essential workers” or people who volunteered for research may get priority too. If there’s an explosive local outbreak, vaccinating everyone nearby would limit the spread.

Who’s in charge? On Friday, a National Academy of Medicine committee announced it will issue its recommendations by early autumn. There’s also an advisory committee within the U.S. Centers for Disease Control and Prevention, which will implement the plan.  Ideally, they will collaborate.

How will it be distributed?

Companies have said they’ll defer to the federal government. But experts, noting the disastrous distribution of PPE and tests, say we should look to the multi-channel distribution model of flu vaccines. They say it should be available from governments and doctors — but also directly from the companies, via CVS, Walgreens and other local pharmacies.

“It’s still inconceivable that we’ll be able to get vaccines to 330 million in three to six months,” Dr. Robert Wachter, chair of the Department of Medicine at UC San Francisco, tweeted this past week. During the 2009 swine flu epidemic, he noted, we vaccinated about one-quarter of all Americans — and that took six months.

Vaccinating 80 to 100 million of the nation’s most vulnerable people, including healthcare workers, “might be do-able by mid-’21,” he said.

A doctor takes blood samples for use in a coronavirus vaccine trial in Oxford, England, Thursday June 25, 2020. (John Cairns, University of Oxford via AP)

Not everybody wants one.

Even people who believe in vaccines are showing reluctance to get the COVID-19 vaccine. They worry that politics are creating undue pressure, and corners will be cut in the rush to produce. Only about half of Americans say they would get a COVID-19 vaccine, according to a May poll from The Associated Press-NORC Center for Public Affairs Research. One-third weren’t sure and one-fifth would refuse, citing safety concerns.

If a vaccine is 50% effective, and 50% of the population gets vaccinated, then only 25% of the population is protected, said Ernst.

That’s far short of the 70% protection needed to stop this pandemic. The only solution is to make a better vaccine — and convince more people to take it.

“We’re not going to get this disease under control by just vaccinating health care workers and kindergarten teachers,” said Ernst.

“We need to be thinking about how are we going to convince people to comply with vaccinations,” he said, “so that we’ve got a sufficient amount of the population covered to actually get COVID-19 under control.”

Source: Orange County Register

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