This is the last article in a six-part series on “two years and counting” for the coronavirus. Click HERE to read the series.
Health officials are coming to realize that while pushing COVID-19 vaccines to the market in record time likely saved hundreds of thousands of lives in America, it also meant they didn’t get the dosing decisions exactly right.
Now, as the world enters year three of the coronavirus crisis, it’s becoming clear that two doses of an mRNA shot from Pfizer-BioNTech or Moderna, the most popular type of vaccine in the U.S., isn’t working as well as hoped. A third booster shot is quickly becoming mandatory in many places for those who want to consider themselves fully vaccinated, and health experts are already enmeshed in a debate about the timing of a fourth shot.
Meanwhile, Pfizer and BioNTech said in January that they had begun to examine whether their vaccine’s original formulation is still effective against a virus that is evolving quickly, with the vaccine-evading omicron variant sweeping the globe and raising questions about other variants lurking.
The Centers for Disease Control and Prevention is downplaying the need for a fourth shot. “Our strategy has to be to maximize the protection of the tens of millions who continue to be eligible for a third shot,” CDC Director Rochelle Walensky said last month.
West Virginia Gov. Jim Justice, a Republican, is demanding permission from the federal government to offer fourth shots to at least his at-risk population.
SEE ALSO: Americans will be cleaning up from the coronavirus for years, experts warn
The Johnson & Johnson shot, a non-mRNA vaccine that was billed as a slightly less-effective one-dose answer, now looks like it should have been a two-dose solution.
The nation’s most prominent voice in the pandemic, Dr. Anthony Fauci, seems to be getting the public ready for an annual vaccination like the flu shot.
The result is a patchwork of recommendations and expectations, leaving some Americans eager for whatever the scientists prescribe and others questioning the changing guidance and wondering whether anything will tame the virus.
It turns out that the middle of an economy-shattering pandemic isn’t the best time to try to get the medical details right.
“If there were no pandemic and we were just starting from scratch to create a COVID vaccine, a longer interval might well have been chosen for the clinical trials and [drugmakers might have] chosen a third dose right at the beginning,” said Dr. William Schaffner, an infectious diseases specialist at Vanderbilt University.
Current recommendations are for a booster shot. Those who got the J&J vaccine are urged to get a booster shot after two months, preferably with an mRNA version. Those who got the two-dose series of Pfizer-BioNTech or Moderna mRNA versions are told to get a booster five months after completing the initial round.
That is down from the six months scientists originally recommended and a far-shorter interval than they wanted.
“We knew there’d be waning. We didn’t know the extent of it and when it would show up. There was hope it would take a year or two. It turns out it took five or six months,” said Dr. Eric Topol, a professor of molecular medicine and executive vice president at Scripps Research.
Peter Hotez, an infectious diseases expert at the Baylor College of Medicine, said he’s been calling the mRNA versions a three-dose version since the beginning of the year.
“When you gave those first two doses just three, four weeks apart, you practically ensured immunity would wane and require a booster. That’s true of most vaccines we administer,” he tweeted in early December.
Racing the virus
COVID-19 was first detected in China in late 2019, and cases reached the U.S. soon afterward. By spring 2020, vaccine manufacturers were hard at work. The Trump administration announced an ambitious plan that May to deliver hundreds of millions of shots by the end of the year.
Trials were sped, the Food and Drug Administration gave emergency use authorization, and the public vaccination campaign began in December 2020.
Roughly 63% of Americans, including 74% of adults, were fully vaccinated as of Jan. 25. About 42% of them got a booster shot as recommended.
Getting a series of shots for the same disease is common. People are accustomed to a yearly flu shot, and infants get three doses against hepatitis B and four diphtheria, tetanus and pertussis (whooping cough) vaccines within the first 15 months of their lives. A recurring tetanus shot is recommended for adults every 10 years. Americans older than 50 receive the Shingrix vaccine for shingles in two doses, two to six months apart, and there is no recommendation for another booster.
The science on the coronavirus and the vaccines, however, isn’t settled.
“The third shot of an mRNA could not only do what we absolutely know it does, [which] is it dramatically increased the level of protection. But from an immunological standpoint, it could very well increase the durability of protection,” Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases, told ABC’s “This Week” in mid-December.
He said the results won’t be clear “until you just follow it over a period of months.”
Scientists are uncertain because COVID-19 is new in humans and they are learning in real time. Shifts in the shape of the virus create new variants of concern, forcing the medical community to reevaluate the power of the vaccines.
“We had that additional curveball here because COVID mutates. It’s not like measles, which basically is solid like a rock,” Dr. Schaffner said.
He said a booster shot spurs even more antibody response, “and it takes them much longer to slide down.” In the case of the COVID-19 boosters, it’s also a more diverse antibody response to the coronavirus.
“It becomes more of a shotgun than a rifle. You get better protection against the variants,” he said.
Scientists also say the extra shot will reinforce a response from the body’s T cells, which serve as a kind of long-term immunity factory.
Some places say that, given what scientists know, three doses instead of two should be the bare minimum. Georgetown University, American University and George Washington University in the District of Columbia all said faculty, staff and students who report to campus had to get booster shots by late January to early February.
The Metropolitan Opera in New York City required audience members and staff to get boosters as of Jan. 17, or at least once they are eligible, as extra doses become normalized.
The CDC still considers full vaccination to be two doses of the Pfizer or Moderna vaccine or one shot of the Johnson & Johnson vaccine, despite pressure from some scientists to align the definition with federal recommendations for a booster.
“That definition is not changing,” Dr. Walensky said in a Jan. 5 briefing.
The efficacy of the shots is changing, however, especially in the face of the omicron variant. Among available studies, data from South Africa found two doses of the Pfizer shots provided just 33% protection against infection from the omicron variant but 70% protection against hospitalization.
The J&J shot, meanwhile, appeared to produce little to no neutralizing antibodies against omicron in December lab studies, according to South African researchers, though later studies found that a booster of the J&J vaccine made hospitalization 85% less likely from the new variant.
U.S. officials last year allowed J&J recipients to get boosted with an mRNA dose that should provide greater protection and said in December that mRNA vaccines are “preferred” over the J&J version because of concerns about efficacy and a rare blood-clotting issue linked to the J&J vaccine.
Dosing strategies
It’s easy to look back and question the decisions that resulted in an initial strategy of two doses, taken within weeks of each other, or just one shot. At the time, COVID-19 death rates in the U.S. were soaring and researchers were struggling to find treatments and figure out how best to stop the virus from spreading. Americans were wiping down packages with disinfectant while debating the benefits of wearing masks.
Meanwhile, the Trump administration raced to develop a portfolio of vaccines. It was a hair-on-fire period for drugmakers.
“When we were choosing these candidates in the summer of 2020, we had no idea which ones were going to win,” said Paul Mango, a key health official in the Trump administration.
Six candidates were in the mix, but three emerged by the end of the year.
Pfizer and German partner BioNTech released positive trial results shortly after Election Day and earned FDA emergency use authorization that December for its messenger-RNA vaccine, which teaches the body how to recognize and fight the virus. Moderna followed shortly afterward with a vaccine using the same technology. J&J’s highly efficient version was delayed by an unexplained adverse incident in one participant in fall 2020 and earned FDA emergency use authorization in late February.
Scientists say the drugmaker and government had ample reason to covet a single-dose vaccine when the pandemic was raging and supplies were limited, though it probably should have been a two-dose vaccine from the start.
“There’s nothing magic about the J&J vaccine. In any other circumstance, it would have been a two-dose vaccine,” said Barry Bloom, a research professor of public health and former dean of Harvard T.H. Chan School of Public Health. “The first shot did do a fair amount of efficacy, but we knew perfectly well a second shot would be better.”
The U.S. government and regulators forged ahead with the one-shot vaccine anyway. Initial trials found it 85% effective against severe disease even if the protection against infection was weaker.
It also wanted to give people some protection as soon as possible. Some Americans liked the ease of one visit, and the J&J vaccine was viewed as useful in immunizing the homeless and other transient people who couldn’t be tracked down for a second dose.
Johnson & Johnson said its vaccine will play a critical role in the ongoing fight.
“A growing body of evidence demonstrates that our vaccine provides protection when administered as a single dose for an efficient response to the pandemic and as a booster dose after at least two months to protect against symptomatic COVID-19,” the company told The Washington Times.
The Biden administration in November brokered a deal with J&J and COVAX, a global vaccine-sharing alliance, to provide the vaccine to conflict zones and hard-to-reach places where a one-shot version would be beneficial.
Mr. Mango said the J&J version should have been the export of choice all along. President Biden is relying mainly on shots from Pfizer to fulfill a pledge of donating more than 1 billion shots to needy places around the world.
“I think we would have favored J&J by far,” Mr. Mango said, “because of the ease of transport and ease of storage.”
The U.S. has largely managed to set up cold-chain systems needed to store the mRNA vaccines, but developing nations often don’t have the same capabilities.
“At central or national and subnational storage warehouses across most countries, there may be inadequate amounts of cold rooms and specialized protective and handling equipment,” said a McKinsey & Co. analysis from September. “In most developing countries, there are only a small number of specialized cold rooms, and they are usually stocked with other vaccines that are part of other national immunization programs.”
While pushing for boosters, the Food and Drug Administration is pondering new dosing strategies.
Right now, certain vaccine recipients seeking a booster might avoid side effects by switching to another type of vaccine. Regulators authorized that approach in October.
“I think the opportunities for these heterologous boosts are priceless. It gives those who received Janssen [J&J] — if you’re a young woman, to receive a messenger RNA. And if you’re a young man who has received the messenger RNA, maybe you switch over to the Janssen. We’re in a different place in the pandemic than we were earlier. Vaccines are readily available,” Dr. Helen Keipp Talbot, an associate professor of medicine at Vanderbilt University, said at a CDC advisory meeting.
Treatment alternatives
Although Americans have three vaccine options, others are being developed.
Novavax, a small company in Gaithersburg, Maryland, was one of six vaccine developers in Operation Warp Speed and viewed as a “dark horse” candidate in the vaccine race.
Its protein-based vaccine had positive trial results but was delayed by production and manufacturing issues. Its fortunes are looking better after receiving emergency use authorization in India, Indonesia and the Philippines and the World Health Organization and conditional market authorization — another fast-track route — in the European Union.
The company said on Jan. 31 that it filed a request for emergency authorization from the FDA, citing an overall efficacy of about 90% and a “reassuring safety profile,” according to the company.
Meanwhile, the vaccine produced by AstraZeneca with Oxford University was viewed as a front-runner and became a vaccine of choice in Europe and other places. It never broke through in the U.S. because it faced a series of hiccups and got boxed out by a sufficient supply of other options.
Mr. Biden decided to earmark supplies of the AstraZeneca for donation overseas.
The company said it likely will skip a request for emergency use authorization in the U.S. and push for full FDA approval.
For more information, visit The Washington Times COVID-19 resource page.
• Tom Howell Jr. can be reached at thowell@washingtontimes.com.
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