Getting more shots into more arms

Health officials navigate logistics, old suspicions

Friday, January 29, 2021, Vol. 45, No. 5
By Kathy Carlson

When Meharry Medical College associate professor of microbiology and immunology Donald Alcendor isn’t in the classroom or lab he’s visiting barbershops, salons and small businesses, teaching informally about clinical trials at Meharry for a new COVID-19 vaccine.

Some will ask: “What are you doing coming here, offering this poison to our people?” Others, he says, are willing to listen.

Scientists at Meharry, founded in 1876 to educate African Americans, know well about community skepticism toward the medical establishment rooted in the infamous Tuskegee experiments and other injustices. Information on COVID-19 and vaccination must be conveyed in a clear, “culturally competent manner; the scientific jargon has to go,” Alcendor says.

Some in Nashville, however, clamor for vaccines. The Metro Health Department offers a daily lottery with as many as four people chosen to receive a COVID-19 vaccine on a standby basis. Four is the maximum, based on the largest possible number of leftover vaccines remaining in a vial at the end of the day.

People must apply every day by sending their name and phone number to COVID19VaccineStandby@Nashville.gov. Each day, 12,000 to 13,000 people sign up, says Metro Health Department communications director Brian Todd. “To me that’s an indication of a lot of interest in this vaccine.”

Between these extremes, hundreds of thousands of people across Tennessee wait for their turn to be vaccinated. Vaccine is in short supply here and around the country as the virus that causes COVID-19 mutates and infects more people.

So far in Tennessee, more than 705,000 people have contracted COVID-19, caused by the SARS-CoV-19 virus that first surfaced in late 2019. COVID-19 has killed more than 8,800 Tennesseans and more than 418,000 so far nationwide.

In Tennessee, each of its 95 counties has received at least some vaccine, distributed based on population by the Tennessee Health Department. County-level inventory depends on local uptake, and counties often quickly run out. As of Jan. 22, all but six Tennessee counties – Clay, Hamilton, Putnam, Rhea, Trousdale and White – had limited vaccine available. Vaccine availability changes from day to day.

The TDH states on its website that, as of Jan. 21, the state had received nearly 800,000 doses of vaccine. It has administered more than 438,500 doses of COVID-19 vaccines, with about 90,000 people receiving the required two doses.

Another 32,000 first doses had been given to staff and residents of long-term care facilities. Dr. William Schaffner, professor of preventive medicine in the department of health policy, as well as professor of medicine in the division of infectious diseases at Vanderbilt University School of Medicine, says Tennessee is among the better states in distributing vaccine, but only a small fraction of those old enough to receive the vaccine have received even one dose.

THD spokesman Bill Christian says limited vaccine means, in most cases, the county has a small number of doses and all doses have already been assigned to people with appointments.

As of Jan. 22, some counties had reached Phase 1b in the state’s rollout plan, but none had passed that phase. The state’s plan to roll out the COVID-19 vaccine says supplies may be limited throughout Phase 1, which extends to a Phase 1c.

In Nashville, for example, eligible people wanting vaccines must make an appointment with Metro Health.

Donald Alcendor, Meharry Medical College associate professor of microbiology and immunology, says a clear, simple message is key to widespread acceptance of vaccines.

-- Photograph Provided

“We’re trying to (vaccinate people) in a way that doesn’t put somebody at risk,” Todd explains. “We’re moving vaccine every week into arms, and we’re doing it as safely and as quickly as we can.”

Last Friday, the Knox County Health Department put out word that at 11 a.m. that day, people could sign up to receive a first shot of COVID-19 vaccine the following day. One thousand appointments were available.

“We had thousands of people on our website when the site went live at 11 a.m.,” department spokeswoman Deborah Crouse said in an email response to questions. “In a matter of minutes, all appointment slots were filled.”

Asked how many people the health department could vaccinate at most in one day, Crouse said factors including the supply of vaccine available and staffing will affect the numbers. “For example, on Jan. 2 we held a clinic where KCHD vaccinated 500 people in three hours,” she said. “This past Saturday, we held scheduled appointments all day and vaccinated 1,000.”

The federal government last year pushed and signed contracts with pharmaceutical companies to develop and provide vaccines against COVID-19.

“You and I as taxpayers actually laid a bet” that vaccine developers would succeed with the vaccine, Schaffner says. “As it turns out, we won the bet because the vaccine is 95% effective.”

The U.S. Food and Drug Administration has approved two companies – Pfizer-BioNTech and Moderna – to offer vaccines under emergency use authorizations (EUAs), and other companies are racing to be able to offer their own vaccines.

Challenges remain, both in manufacturing enough of the perishable vaccines and persuading enough people to receive not only the first shot, but also a second required booster. The vaccines target the spike protein that the SARS-CoV-2 virus uses to enter cells and infect people.

They cannot cause COVID-19, and scientists have provided evidence of safety and efficacy in order to gain EUAs. Any future vaccines administered under EUAs will carry the same assurances.

The Pfizer-BioNTech and Moderna vaccines being rolled out use messenger RNA (mRNA) that encodes the COVID-19 spike protein, Meharry’s Alcendor explains. The mRNA, placed inside a protective nanoparticle, is injected into the body. The person’s body makes the spike protein, which his/her immune system recognizes as a foreign protein and begins to make antibodies.

After receiving the first and second shot, six to eight weeks from start, the antibodies will prevent virus infection by attaching to the real spike protein on the virus and prevent it from invading cells and giving a person COVID-19.

These are the first mRNA vaccines ever used to fight a disease in humans. When both doses are given, they’re effective in 95% of people up to age 65 and across racial groups, although effectiveness drops off among those over 65, Alcendor notes.

Sullivan County residents wait in line and staging areas at the Bristol Dragway on a Thursday morning in erly January hoping to receive a COVID-19 vaccine given by the county health department.

-- Photo By David Crigger/Bristol Herald Courier Via Ap

Side effects so far are similar to those that typically occur with any vaccine – soreness at site of injection, slight fatigue, chills and fever. There have been rare serious side effects, notably anaphylaxis, a severe allergic reaction that can be life-threatening if not treated promptly.

Anaphylaxis has not been fatal, but in some cases has required hospitalization and intubation, Statnews reported this month, citing CDC data. Anaphylactic reactions often occurred in people with a history of allergies, including a previous episode of anaphylaxis.

COVID-19, however, has killed more than 418,000 people in the United States and 2 million-plus worldwide. Moreover, the long-term effects of COVID-19 are just beginning to be understood, as more people report lingering long-haul symptoms that range from annoying to incapacitating.

Two companies likely to seek EUAs for their vaccines are the Oxford University-AstraZeneca partnership and the American manufacturer Johnson & Johnson/Janssen. These are adenovirus vector-based vaccines, different from mRNA vaccines and using an adenovirus vector to carry the encoded spike protein into cells in the body, as a taxi delivers a passenger to a location, Alcendor says.

Adenoviruses are common in humans and cause minor ills like the common cold. The adenovirus vector used in the vaccine is usually stripped of essential genes, making them less likely to cause disease. These vaccines cannot give people COVID-19, he adds.

Scientists have been able to reach 90% effectiveness with the Oxford-AstraZeneca vaccine by first giving a half dose and then a full dose one month later, an AstraZeneca news release states.

Johnson & Johnson is expected to submit clinical trial data to the FDA in the next couple of weeks, Schaffner adds. Based on previews of those data, he says he anticipates that it will get an EUA and will be an additional source of vaccine supply.

The J&J vaccine requires only one dose and is refrigerator-stable, two big advantages compared to Moderna and Pfizer, which require two doses and freezing, the Pfizer at ultracold temperatures that not all potential providers can maintain.

Meharry, among other institutions, is conducting Phase 3 trials to determine safety and efficacy of a vaccine from a third company, Novavax of Gaithersburg, Maryland. This vaccine uses a third approach and introduces the protein directly into the body without a vector. It’s called a purified spike protein-based vaccine and includes a chemical called an adjuvant that enhances a person’s immune response to the spike protein.

Protein-based vaccines have already been licensed for hepatitis and shingles.

“You don’t have to rely on the body to make the spike protein,” Alcendor says, “and the protein is likely more stable.” Adding an adjuvant with the protein helps boost the immune response.

[See box on the Novavax clinical trial and on how to apply to participate.]

As vaccine development continues, efforts to get the two authorized vaccines into arms continues.

“The rollout of the vaccine has had more bumps in the road than I’d like. … It’s been more chaotic at the national level than people anticipated,” Schaffner says. “We hope that going forward a lot of these difficulties will be addressed.”

Even as vaccines get introduced, SARS-CoV-19 keeps mutating, and there’s not enough information yet on how mutations may affect the efficacy of vaccines.

Hamilton County Health Department worker Megan Robbins helps administer a dose of the COVID-19 vaccine at the successful drive-thru near the Hubert Fry Center at the Tennessee Riverpark.

-- Photo By C.B. Schmelter | Chattanooga Times Free Press Via Ap

Vaccines are based around blocking the spike proteins on the surface of the virus, the key by which the virus enters cells, says Dr. Jonathan Moorman, vice chair of research and scholarship, professor of medicine and chief of the division of infectious diseases at East Tennessee State University’s Quillen College of Medicine.

A mutation in the spike protein will affect a vaccine’s efficacy, he says. A mutation elsewhere in the virus probably will not affect the vaccine’s efficacy, he says.

Vanderbilt’s Schaffner says that if a mutation occurs in the spike protein, the next question is whether the mutation is enough to lower the vaccine’s effectiveness, and if so, how much less effective will the vaccine be. Those questions will be studied in great detail.

To Schaffner, “It’s clear that the faster we can get people vaccinated and reduce the capacity of the virus to spread and multiply, (the better) we can stay ahead of mutations that can change (the effectiveness of vaccines).”

He and Moorman say it’s not yet known whether SARS-CoV-19 will mutate so often that people will need to take different COVID-19 vaccine periodically, as they do with annual shots for the rapidly mutating “regular flu.”

In the meantime, Schaffner says, people need to follow the standard recommendations to reduce COVID-19 transmission: Wearing masks, social distancing, steering clear of large groups, staying home and washing hands. “And when it’s our turn, let’s all get vaccinated. It’s really a very, very nasty virus.”

Even after people receive vaccines, they should continue to wear masks and take other precautions as the vaccine’s effectiveness grows over time. Also, the current vaccines will not work in 5% of those receiving them.

Alcendor and Schaffner both say people need not fear they’ll be “guinea pigs” receiving a vaccine that was made at record speed. COVID-19 vaccines were the result of years of prior research and technology development. Clinical trial phases that traditionally were done one after another, in a series, were done at the same time, reducing the time to EUA.

All safety requirements for the phases were followed and met. And government funding made it possible for vaccine manufacturers to build production facilities at the same time development was taking place, saving more time.

State Sen. Brenda Gilmore, D-Nashville, recently received her first inoculation.

“I am feeling great after receiving my first dose of the coronavirus vaccine because I know I am helping put an end to this pandemic,” she says. “I could not be more proud of the scientists and doctors at Meharry who participated in the development of a safe, reliable vaccine and are now administering shots to deal this pandemic a knockout blow.”

Vaccines are critically important, Gilmore adds, but even more so for African Americans and Latinos who have suffered higher rates of infection and death than their white counterparts.

“Our hometown, historically black medical college is putting an incredible effort into fighting this virus and protecting our community,” Gilmore adds.

“This vaccine works. I trust the work they’re doing and every person, black, white or brown, should get in line for a shot as soon as they can.”