Vaccine Passes First Bar With Approval From Scientists, But Questions Remain

The arrival of the Pfizer-BioNTech vaccine in states across the country took place with great fanfare as media marked the first inoculation. An African American nurse at the Long Island Jewish Medical Center in New York became the poster child for a campaign that will last for months in the hopes of quelling the pandemic.

But as the first group of health care workers await their inoculation, warnings about the vaccine are flying across social media, firing up fear at a time when distrust of government runs high. 

The first vaccine was tested and approved at a breakneck speed, propelled by billions of taxpayer dollars. Top immunologists, vaccinologists and other specialists in a U.S. Food and Drug Administration drug review committee approved it last week. A parallel group of scientists representing Oregon, Washington, California and Nevada gave the go-ahead on Sunday.

A majority of the FDA committee -- 17 to 4 --  voted to approve the vaccine by Pfizer, based in New York, and BioNTech, a German company. The Western states group was unanimous is saying the vaccine was safe.

But it was only approved on an emergency basis. The vaccine has not gone through the more rigorous examination required by the FDA for prescribed medications.

“Emergency use authorization is not a licensure,” said Dr. Louis Picker, one of Oregon Health & Science University’s top vaccine experts and a member of the Western review group. “It means that it’s still an experimental vaccine.”

No serious side effects emerged during the clinical trial of 44,000 people. But the Pfizer-BioNTech trials are not over. The U.S. study is not expected to wrap up until 2023, according to the companies’ filings. https://clinicaltrials.gov/ct2/show/NCT04368728?term=BNT162b2&draw=2&rank=4

“The decision was made that given the force of infection of the COVID-19 epidemic now, that the benefits of vaccination far outweigh the risks,” Picker told The Lund Report. “We can’t comment on long-term side effects because there are no data.”

Review of Safety Data

The review committees looked at safety data with a median of two months, with some covering a shorter term and some longer. That timeframe is key, Picker said. Most side effects from vaccines emerge within eight weeks after inoculation. 

The Pfizer-BioNTech data showed what scientists expected: pain and inflammation at the injection site, fatigue, headaches, chills and joint or muscle pain.

“Every vaccine we’ve ever made has had side effects in some people, including the flu vaccine,” Picker said. “Until you put it into hundreds of thousands of people you don’t know” about possible long-term effects.

Two people in Britain with a history of severe allergies suffered anaphylactic shock after getting an injection. That didn’t happen in the U.S. trials but people with severe allergies were screened out.

The risk of a severe allergic reaction is rare but can happen with any vaccine, scientists said. That’s why children are told to sit for 15 minutes after getting inoculated, for example, and why adults are asked on forms before getting a vaccine if they’ve ever had an allergic reaction to one so the pharmacist can be prepared. The two Britons, who carried EpiPens, were treated and are fine, British authorities said.

But their reaction fanned fears. Among them, that the Pfizer vaccine can alter DNA. Experts say that fear is unwarranted.

The anxiety is based on the fact that the vaccine uses messenger RNA, or mRNA, the component in the body that acts as a master programmer in the production of protein. The lab-produced mRNA used in the vaccine is programmed to orchestrate the production of the spike protein, which sits on the surface of the novel coronavirus and is the means through which the virus infects cells.

Messenger RNA is fragile, so it’s enveloped in lipids to protect it. After injection, the mixture is taken up by cells, which the mRNA turns into spike protein factories. This is where the multifaceted immune system comes in. One key component in that system is so-called antigen presenting cells, a parent and teacher of the immune system. They produce antibodies -- B cells -- which are trained to make antibodies that block the virus from infecting cells. They also produce killer T cells, or cytotoxic cells, which are the body’s attack troops against virus-infected cells. Those produced by the antigen-presenting cells involved in this cycle are trained to kill cells infected with the novel coronavirus.

There’s no DNA involved in the process, and, with limited exceptions, mRNA does not produce DNA in people. Rather, DNA serves as a template to create RNA. The possibility of mRNA vaccines altering the genome are not something to worry about, Picker said.

“That concern is really, really down there in terms of probability of that happening,” Picker said.

Vaccine researchers have worked for years on DNA-based vaccines, and scientists have worried that they could cause a mutation. But Picker said no evidence of DNA damage has ever been found, and scientists have been working on them for decades.

Other fears have circled around questions about a turn off switch: Does the vaccine turn cells into spike protein plants that remain in production forever?

Picker brushed that aside, too, saying RNA degrades quickly. When that happens, cells stop producing spike protein. Some might die; others will return to their previous state.

“It’s not permanent,” Picker said of the mRNA response.

More Vaccines Coming

Later this week, Picker is expecting to return to trial data in the review of the mRNA vaccine made by Moderna, a Cambridge, Massachusetts company. It will be reviewed by the FDA’s committee for the second time this Thursday. If the committee endorses it, it could be approved the next day, as the Pfizer-BioNTech vaccine was.

In their trials, both vaccines showed about 95% effectiveness in preventing COVID-19. That’s about as protective as a vaccine can be. Another vaccine that could reach the review process early next year is made by the University of Oxford in collaboration with AstraZeneca, a British company. It’s based on a cold virus that infects chimpanzees and which acts as a vehicle to carry part of the spike protein into the body. That fires up the immune process in much the same way as the mRNA vaccines, Picker said. Antigen presenting cells process the protein and produce B cells and T cells to neutralize the virus and attack infected cells.

But it’s much less protective than the two mRNA vaccines. So far the trial data have shown 62% efficacy. A mistake by a contractor who gave people a half first dose and full second dose showed 90% efficacy. Scientists don’t understand why.

The efficiency of vaccines comes down to small decisions such as which molecules to include in the vaccine, Picker said.

“All those decisions impact efficacy,” Picker said. “It may be that the Oxford vaccine needs to be tweaked to work better.”  

He said the data showed that BioNTech, which developed the Pfizer-BioNTech vaccine, made a lot of right choices to surpass 90% efficacy.

Picker will not be the first in line for vaccination. OHSU will start vaccinating its employees on Wednesday, starting with health care personnel and cleaning and other staff who are at the highest risk of exposure to the virus at work. It will put people 55 and older, have a medical condition that puts them at high risk or belong to a minority group at the very front. 

He doesn’t treat COVID-19 patients. He works in a lab. But when his turn comes, he’ll happily put his arm out.

“I would be delighted to get the Pfizer vaccine,” Picker said. “I was very impressed with the data that I saw.”

You can reach Lynne Terry at [email protected] or on Twitter @LynnePDX.

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