The Coronavirus in America: There will not be a vaccine soon.

Pandemic

2020-04-18 / www.nytimes.com




The coronavirus is spreading from America’s biggest cities to its suburbs and has begun encroaching on the nation’s rural regions. The virus is believed to have infected millions of citizens and has killed more than 34,000.

There will not be a vaccine soon.

Even though Limited human trials of three candidates — two in the U.S.A and one in China — have already begun, any effort to make a vaccine will take at least a year to 18 months. Researchers differed sharply over what should be done to speed the process. Modern biotechnology techniques using RNA or DNA platforms make it possible to develop candidate vaccines faster than ever before.
But clinical trials take time, in part because there is no way to rush the production of antibodies in the human body.
Also, for unclear reasons, some previous vaccine candidates against coronaviruses like SARS have triggered “antibody-dependent enhancement,” which makes recipients more susceptible to infection, rather than less. In the past, vaccines against H.I.V. and dengue have unexpectedly done the same.
A new vaccine is usually first tested in fewer than 100 young, healthy volunteers. If it appears safe and produces antibodies, thousands more volunteers — in this case, probably front-line workers at the highest risk — will get either it or a placebo in what is called a Phase 3 trial.
It is possible to speed up that process with “challenge trials.” Scientists vaccinate small numbers of volunteers, wait until they develop antibodies, and then “challenge” them with a deliberate infection to see if the vaccine protects them.
Challenge trials are used only when a disease is completely curable, such as malaria or typhoid fever. Normally, it is ethically unthinkable to challenge subjects with a disease with no cure, such as Covid-19.
But in these abnormal times, several experts argued that putting a few Americans at high risk for fast results could be more ethical than leaving millions at risk for years.
“Fewer get harmed if you do a challenge trial in a few people than if you do a Phase 3 trial in thousands,” said Dr. Lipsitch, who recently published a paper advocating challenge trials in the Journal of Infectious Diseases. Almost immediately, he said, he heard from volunteers.
Others were deeply uncomfortable with that idea. “I think it’s very unethical — but I can see how we might do it,” said Dr. Lucey.
The hidden danger of challenge trials, vaccinologists explained, is that they recruit too few volunteers to show whether a vaccine creates enhancement, since it may be a rare but dangerous problem.
“Challenge trials won’t give you an answer on safety,” said Michael T. Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy. “It may be a big problem.”
Dr. W. Ian Lipkin, a virologist at Columbia University’s Mailman School of Public Health, suggested an alternative strategy. Pick at least two vaccine candidates, briefly test them in humans and do challenge trials in monkeys. Start making the winner immediately, even while widening the human testing to look for hidden problems.
As arduous as testing a vaccine is, producing hundreds of millions of doses is even tougher, experts said.
Most American vaccine plants produce only about 5 million to 10 million doses a year, needed largely by the 4 million babies born and 4 million people who reach age 65 annually, said Dr. R. Gordon Douglas Jr., a former president of Merck’s vaccine division.
But if a vaccine is invented, the United States could need 300 million doses — or 600 million if two shots are required. And just as many syringes.
“People have to start thinking big,” Dr. Douglas said. “With that volume, you’ve got to start cranking it out pretty soon.”
Flu vaccine plants are large, but those that grow the vaccines in chicken eggs are not suitable for modern vaccines, which grow in cell broths, he said.
European countries have plants but will need them for their own citizens. China has a large vaccine industry and may be able to expand it over the coming months. It might be able to make vaccines for the United States, experts said. But captive customers must pay whatever price the seller asks, and the safety and efficacy standards of some Chinese companies are imperfect.
India and Brazil also have large vaccine industries. If the virus moves rapidly through their crowded populations, they may lose millions of citizens but achieve widespread herd immunity well before the United States does. In that case, they might have spare vaccine plant capacity.
Alternatively, suggested Arthur M. Silverstein, a retired medical historian at the Johns Hopkins School of Medicine, the government might take over and sterilize existing liquor or beer plants, which have large fermentation vats.
“Any distillery could be converted,” he said.

Treatments are likely to arrive first.

In the short term, experts were more optimistic about treatments than vaccines. Several felt that so-called convalescent serum could work.
The basic technique has been used for over a century: Blood is drawn from people who have recovered from a disease, then filtered to remove everything but the antibodies. The antibody-rich immunoglobulin is injected into patients.
The obstacle is that there are now relatively few survivors to harvest blood from.
In the pre-vaccine era, antibodies were “farmed” in horses and sheep. But that process was hard to keep sterile, and animal proteins sometimes triggered allergic reactions.
The modern alternative is monoclonal antibodies. These treatment regimens, which recently came very close to conquering the Ebola epidemic in eastern Congo, are the most likely short-term game changer, experts said.
The most effective antibodies are chosen, and the genes that produce them are spliced into a benign virus that will grow in a cellular broth.
But, as with vaccines, growing and purifying monoclonal antibodies takes time. In theory, with enough production, they could be used not just to save lives but to protect front-line workers.
Antibodies can last for weeks before breaking down — how long depends on many factors, Dr. Silverstein noted — and they cannot kill virus that is already hidden inside cells.
Having a daily preventive pill would be an even better solution, because pills can be synthesized in factories far faster than vaccines or antibodies can be grown and purified.
But even if one were invented, production would have to ramp up until it was as ubiquitous as aspirin, so 300 million Americans could take it daily.

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