Pfizer COVID-19 Vaccine Launches in the US

Today, healthcare workers rolled up their sleeves for injections of the first COVID-19 vaccine licensed by the US Food and Drug Administration.It is an impressive debut for the world’s first mRNA vaccine, jointly developed by Pfizer and BioNTech. Scientists have been developing mRNA vaccine technology for more than two decades with the dream that it would one day be used for rapid pandemic vaccine development.

That dream came true on Friday, December 11, when the FDA allowed the vaccine to be used after analyzing the results of a 44,000-person clinical trial that showed it was 95% effective in preventing COVID-19. On Sunday, the first FedEx and UPS trucks left Pfizer’s manufacturing plant in Portage, Michigan, where the vaccines were manufactured and loaded into boxes filled with dry ice. Vaccines now offer hope for relief after the deadliest week of the pandemic in the US.

“It’s really an amazing scientific achievement,” says Srilatha Edupuganti, infectious disease physician at the Hope Clinic at the Emory Vaccine Center. “I am very excited about this vaccine, which is going to prevent illness and death.”

Daniel Hoft, director of the Saint Louis University Vaccine Development Center and a member of the National Vaccine Advisory Committee, says he is also pleased with the news. “No one thought that the first vaccines tested in Phase 3 could be as effective without major safety concerns. So this is really a great event, ”he says in an email.

The supply of the vaccine will be limited and there will not be enough for everyone who wants it. In July, the US government paid $ 1.95 billion to preorder 100 million doses, enough to vaccinate 50 million people. Pfizer expects up to 25 million doses to be distributed in the US by the end of the year, with the remainder to be delivered in the first months of 2021.

Vaccinating the country, let alone the world, will require additional COVID-19 vaccines to be successful in trials and gain clearance from the FDA. Later this week, the FDA and its vaccine advisory committee will meet again to vote on the approval of a highly effective mRNA vaccine manufactured by Moderna. And depending on the results of ongoing phase 3 clinical trials, three more companies – AstraZeneca, Johnson & Johnson and Novavax – could be ready to apply for their vaccines in the first months of 2021.

Although the FDA worked with remarkable speed to review Pfizer’s data, the agency’s words and actions also indicate that its leaders largely resisted political pressure to improperly expedite the vaccine’s authorization. Five other countries – Bahrain, Canada, Mexico, Saudi Arabia and the United Kingdom – licensed the vaccine before the United States.

The FDA gave the vaccine the green light for use in people 16 years of age and older through a pathway called emergency use authorization (EUA), which requires 2 months of follow-up after clinical trial participants receive their second injection. A formal FDA approval will require 6 months of follow-up. Pfizer plans to submit a Biologics License Application for that formal approval in 2021.

Pfizer and BioNTech first announced a collaboration to make a vaccine for COVID-19 on March 17. Although the couple began working together on experimental flu vaccines in 2018, they had never conducted a large clinical trial to demonstrate the efficacy of an mRNA vaccine. The first volunteers injected themselves in Germany in April and in the United States in May. The Phase 3 study began in July, and the companies announced the preliminary results of that trial with great success in November.

A later peer-reviewed article showed that the vaccine was approximately 50% effective during the three weeks between the first and second injections. The vaccine was approximately 90% effective in the first week after the second injection and 95% effective 7 days after the second injection, which is the main data point that Pfizer emphasized when looking up its EUA (N. Engl. J. Med. 2020, DOI10.1056 / NEJMoa2034577).

That level of efficacy is “really remarkable,” says Asunción Mejías, an infectious disease doctor at the Center for Vaccines and Immunity at the Nationwide Children’s Hospital Research Institute, in an email. A big question is how long that immunity will last. “We hope that the efficacy of the vaccine remains as high,” he says, but herd immunity could be achieved even “with vaccines that are even slightly less effective.” Pfizer plans to monitor the vaccine’s efficacy and safety in the 44,000 trial volunteers for two years after their second dose.

On Dec. 10, the FDA’s Vaccine Advisory Committee, comprised of infectious disease physicians and vaccine scientists, voted 17-4 in favor of authorizing the vaccine. At the end of the 9 a.m. meeting, some members of the committee objected to authorizing the use of the vaccine in 16 and 17-year-olds, including H. Cody Meissner, chief of pediatric infectious diseases at the University School of Medicine. from Tufts. Meissner said she wanted the vaccine to be licensed for people 18 and older, but the data was insufficient to justify application to 16 and 17 year olds. He requested, in vain, that the FDA change its wording to authorize the vaccine in adults over 18 years of age. Finally he abstained during the vote.

However, it is unlikely that most young people will be the first to receive the vaccine. The U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices said the first wave of vaccines should be given to two groups: healthcare workers treating patients and residents of long-term care facilities. The next wave, which won’t start until 2021, will include the remaining healthcare workers, other essential workers and adults with high-risk medical conditions like cancer, kidney disease and diabetes.

Now that the vaccine is licensed, the difficult task of distributing and administering it begins. Vaccines must be shipped and stored at approximately –70 ° C, and Pfizer is using dry ice and special containers to keep them cool. Upon arrival, the vaccine can be kept refrigerated at 2-8 ° C for up to five days. Pfizer says it is betting on a “just-in-time” system with minimal intervals between manufacture, shipment and administration of vaccines.

Medical centers have begun prioritizing who should get the vaccine first among their staff. “States are asked to basically figure it out themselves. It does not come from the federal level, ”says Edupuganti. Although the government offers the vaccine for free, states and medical facilities bear the cost of administering it, keeping track of recipients, and ensuring they return for the booster shot after 3 weeks.

Since no one has ever manufactured such large quantities of an mRNA vaccine before, some delays in the production of the vaccines should come as no surprise. Pfizer has already experienced a delay in producing enough raw materials for its vaccine, causing it to lower its 2020 target from 100 million doses to 50 million.

Some questions remain about who the Pfizer vaccine will work for and how well it will work. The company does not know if the vaccine is safe and effective for children under 16 years of age, for pregnant women and for people who are immunosuppressed. The company is planning additional studies to evaluate the vaccine in these groups.

And while the vaccine clearly protects people against the disease, Pfizer is still collecting data to see if it also mitigates the spread of the infection. Until we know it, it is important that vaccinated people follow measures such as the use of masks and social distancing to avoid the involuntary spread of the virus, says Mejías.

Doctors will also need to be on the lookout for rare side effects that can only be found once the vaccine is administered to millions of people, Edupuganti says. Two people in the UK with a history of severe allergies experienced anaphylaxis after receiving the injection. The CDC recommends that doctors monitor everyone for 15 minutes after the injection and people with a history of anaphylaxis for 30 minutes.

People receiving the Pfizer vaccine should anticipate side effects, which include fatigue, headache, muscle pain, and chills. These types of reactions are within the range of side effects produced by existing vaccines, says Edupuganti. “This COVID-19 vaccine is more reactogenic than a flu vaccine, but less reactogenic than some vaccines, such as the herpes zoster vaccine,” he says.

While scientists anticipated licensing the Pfizer vaccine last week, two other groups reported disappointing results from trials of COVID-19 vaccines based on more traditional recombinant protein vaccine technology. CSL Behring and the University of Queensland announced that they would be abandoning their vaccine, while Sanofi and GlaxoSmithKline said their trial would be delayed.

The Queensland researchers modified the coronavirus spike protein with amino acids derived from an HIV protein intended to boost immunity. Unexpectedly, vaccine recipients develop antibodies against HIV. Follow-up testing confirmed that these people were not actually infected with HIV, but CSL and the Australian government decided to withdraw the vaccine as changing existing HIV testing procedures was deemed too challenging.

The Sanofi-GSK vaccine produced good immune responses in people younger than 50, but not in people older than 50, probably because the concentration of the antigen, the spike protein, was not high enough, the companies say. Although the companies were planning to start a Phase 3 trial of the vaccine this month, they now plan to reformulate it and test it in a Phase 2b study starting in February. The original goal of having the vaccine licensed and distributed by mid-2021 has been pushed back to the end of the year.

“This slows down the clinical development of these vaccines, but they can still be optimized and contribute to vaccination plans around the world to overcome the pandemic,” says Hoft of Saint Louis University.

More unexpected news came from the Gamaleya National Center for Epidemiology and Microbiology, which says AstraZeneca plans to combine parts of the COVID-19 vaccines from each group. Both vaccines are made with adenoviral vectors that carry the SARS-CoV-2 spike protein gene into cells. The AstraZeneca vaccine uses two injections of a chimpanzee-derived adenovirus, while the Gamaleya vaccine uses one injection of each of two different human-derived adenovirus strains called Ad5 and Ad26. AstraZeneca will begin a trial at the end of the year testing an injection of its vaccine with an injection of the Ad26-based Gamaleya vaccine.

Johnson & Johnson is also developing an Ad26-based vaccine for COVID-19, although it is betting that a single injection will be enough for protection. J&J recently said that it will reduce the size of its Phase 3 study from 60,000 to 40,000 volunteers, as the rampant spread of the coronavirus in the US should make it easier to know if the vaccine is working with fewer people.