What We Know About the C.D.C.’s Covid-19 Vaccine Plans

Posted on by Lori Jia

The New York Times, September 2, 2020 (with Katie Thomas)

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In planning documents sent last week to public health agencies around the country, the Centers for Disease Control and Prevention described preparations for two coronavirus vaccines they refer to simply as Vaccine A and Vaccine B. The technical details of the vaccines, including the time between doses and their storage temperatures, match well with the two vaccines furthest along in clinical tests in the United States, made by Moderna and Pfizer.

Here’s what you need to know about how the vaccines work, how they’re being tested and how they might be rolled out to the public — if, and it’s still a big if, they are proven to work.

Vaccines can take many different forms. The most common in use today contain inactivated viruses, weakened live viruses, or pieces of proteins. Moderna and Pfizer are testing a new kind of vaccine that has never before been approved for use by people. It contains genetic molecules called messenger RNA. The messenger RNA is injected into muscle cells, which treat it like instructions for building a protein — a protein found on the surface of the coronavirus. If all goes well, the proteins stimulate the immune system and result in long-lasting protection against the virus.

Both vaccines have gone through extensive early tests, but we still don’t know for sure if they’re safe and effective.

Once vaccines are designed, they go through four stages of testing. In the preclinical stage, researchers test them on animals. For Covid-19, these animals include hamsters and genetically modified mice, both of which can experience some of the same symptoms as humans.

If these tests yield promising results, then the vaccines go into three phases of clinical trials in people.

In Phase 1, doctors give the vaccine to a small number of volunteers. They keep an eye on them to make sure they don’t have any immediate negative reactions. It’s not uncommon for people to feel achiness in their muscles or even a mild fever, but these mild symptoms typically don’t last long.

In Phase 2 trials, scientists give the vaccine to hundreds of people split into groups, like children and older adults, to determine whether the vaccine acts differently in them. In both Phases 1 and 2, researchers analyze the blood of volunteers to see if their immune systems are learning to fight the virus with antibodies and immune cells that can kill infected cells.

Finally, in Phase 3 trials, scientists give the vaccine to tens of thousands of people and a placebo to tens of thousands of others.

Moderna and Pfizer are currently testing their candidates in Phase 3 trials. In their earlier human studies, neither vaccine produced serious side effects. Both vaccines provoked people’s immune systems to make antibodies that can neutralize the coronavirus.

That’s encouraging. But that alone does not reveal whether a vaccine works or not.

Only a Phase 3 trial can establish whether a vaccine is safe and effective enough to be approved for widespread use.

In such a trial, volunteers are randomly assigned to receive either the vaccine or the placebo. They don’t know which one they are given, nor do their doctors. By “blinding” the trial, researchers ensure that no bias creeps into the study.

A Phase 3 trial collects data about the symptoms volunteers experience after their injection, and whether they become infected with the coronavirus. After “unblinding” the data, researchers compare the rates of infection and adverse side effects between people who receive the vaccine and those who receive the placebo.

If significantly more people get Covid-19 on the placebo than the vaccine, that is evidence that the vaccine is effective. The F.D.A. has indicated that vaccine makers should aim for 50 percent protection in order to be considered effective.

In recent days, some federal health officials have said a vaccine could be made available to at least some groups before clinical trials have been completed. An independent body called a Data and Safety Monitoring Board is charged with checking in on clinical trials at certain points to ensure there are no serious safety issues. If the vaccine is harming participants, the trial may be ended early. But if it appeared to be working incredibly well — a scenario that the government’s top infectious disease expert, Anthony S. Fauci, floated in an interview with Kaiser Health News this week — the board could also decide it would no longer be ethical to continue giving some participants a placebo and could end the trial early.

Companies have given varying estimates. Pfizer recently said it was “on track” for seeking government review “as early as October 2020.” Moderna has said it expects to complete enrollment in its Phase 3 trial in September, but has not provided an estimate about when the vaccine might be ready for the public.

Federal officials said in May that the first doses of a vaccine being developed by AstraZeneca, in partnership with the University of Oxford, could be delivered by October. But AstraZeneca, which recently began Phase 3 trials of the vaccine in the United States, is now saying it could supply the first doses of the vaccine in the United States by the end of 2020.

In a recent statement, Pascal Soriot, the chief executive of AstraZeneca, said the company was “putting science and the interest of society at the heart of our work,” adding, “we are moving quickly but without cutting corners.”

The pandemic has prompted a drastic change in how vaccines are developed. Normally, vaccine makers would wait for clinical trials to yield definitive results before moving forward with plans to manufacture a vaccine. This time, many manufacturers have begun preparing in advance for production, getting money from governments to buffer the risk.

The C.D.C.’s planning documents give an indication of the extraordinary complexity of distributing vaccines to hundreds of millions of people in a country with a fragmented health care system. Past experiences serve as a warning about how this undertaking can go awry.

In March 2009, a pandemic strain of influenza known as H1N1 emerged, raising the prospect that huge numbers of people might die. Scientists worked hard to create and test a vaccine for the new flu strain as fast as possible. But large deliveries of the vaccine didn’t start until December, and only 24 percent of Americans received it by April 2010. Fortunately, the new flu strain turned out to be much milder than expected.

That’s not the case with Covid-19. So far, over 25.7 million people have been infected worldwide and 857,920 have died. With the prospect of many more infections ahead, the rapid deployment of a safe and effective vaccine is all the more urgent.

The Centers for Disease Control and Prevention told public health agencies last week that limited doses of a vaccine may be available beginning in late October or November, although that would only be if a vaccine is shown to be safe and effective. According to the documents the agency sent to the public health offices, two million doses of what the C.D.C. labeled Vaccine A — most likely the Pfizer vaccine — may be available by the end of October, with 10 to 20 million doses possibly available by November, and 20 to 30 million by the end of December.

The C.D.C. said the other potential vaccine, Vaccine B — which matches the details of the Moderna vaccine — could have about 1 million doses available by October, 10 million by November, and 15 million by December. Each of the vaccines would require two doses to be effective.

Pfizer and Moderna did not respond to questions about the C.D.C.’s recent guidelines.

In the documents sent to public health agencies, the C.D.C. said certain groups would have priority, beginning with health care workers, essential workers (like police officers or those who work in critical industries like food production), “national security populations,” and workers and residents of long-term care facilities like nursing homes.

Those priority groups include millions of people. At a meeting last week of the Advisory Committee on Immunization Practices of the C.D.C., an agency official presented a slide showing that in the United States, there are about 17 to 20 million health care workers, 60 to 80 million essential workers and about 53 million people older than 65.

On Wednesday, the National Academies of Sciences, Engineering and Medicine unveiled a 114-page plan, sponsored by the C.D.C. and the National Institutes of Health, that proposed a complicated four-phase system for priority.

Probably not. Aside from Moderna and Pfizer, there are 34 other vaccines in clinical trials worldwide. There are over 90 more vaccines confirmed to be in active preclinical testing. Over the next year, 69 of them are slated to go into clinical trials.

Among all of these other vaccines, some may prove more potent than the first ones that are approved. Some may be better in particular for children or older people. Some may turn out to provide a valuable booster to immunity.

Moderna and Pfizer’s vaccines also require a lot of care in their handling. For example, Moderna’s vaccine requires storage at minus 20 degrees Celsius; Pfizer’s has to stay at minus 70. Some of the other vaccines now being developed may be kept at much warmer temperatures, making them easier to distribute in places that don’t have advanced medical facilities.

Copyright 2020 The New York Times Company. Reprinted with permission.