Explainer: How COVID-19 vaccines work
All the COVID-19 vaccines indicate high efficacy against the virus, even though they take very different approaches. Here’s how some of them and vaccine candidates work.
Pfizer and its German-based partner BioNTech use a new approach to making vaccines that uses messenger RNA or mRNA.
This design was chosen for a pandemic vaccine years ago because it’s one that lends itself to quick turnaround. All that is needed is the genetic sequence of the virus causing the pandemic. Vaccine makers don’t even need the virus itself — just the sequence.
In this case, BioNTech researchers used a little piece of genetic material coding for a piece of the spike protein — those studs that cover the surface of the coronavirus and the source of its name. Corona means “crown.”
Messenger RNA is a single strand of the genetic code that cells can “read” and use to make a protein. In the case of this vaccine, the mRNA instructs the muscle cells in the arm to make a particular piece of the virus’s spike protein called the receptor binding domain. Then the immune system sees it, recognizes it as foreign and is prepared to attack when actual infection occurs.
“RNA is like snapchat messages that expire. RNA vaccines do NOT become a permanent part of your body. They are temporary messages instructing cells to make one viral protein temporarily,” Shane Crotty, a virologist at the La Jolla Institute for Immunology, said on Twitter.
“It takes 25 different coronavirus proteins to make a coronavirus, so there is no worry about the RNA making a virus.”
Clinical trials showed Pfizer’s vaccine was 95% effective in preventing symptomatic infections. Pfizer is working to show the vaccine can prevent all infections, including those that don’t cause symptoms. It has also been testing its vaccine against some of the worrying new variants of coronavirus. So far, the studies indicate the vaccine can protect against variants causing concern in South Africa and the UK.
MRNA is very fragile so it’s encased in lipid nanoparticles — a coating of a buttery substance that can melt at room temperature. That’s why Pfizer’s vaccine must be kept at ultracold temperatures of about minus 100 degrees Fahrenheit (minus 75 degrees Celsius). That means special equipment is needed to transport and store this vaccine.
Pfizer’s vaccine won FDA EUA in December and is being delivered to millions of people in the US and UK. The US government has contracted to buy 300 million doses of Pfizer’s coronavirus vaccine.
Side-effects from vaccination are rare and usually mild. They include fever and headache, although a very few people have experienced allergic reactions to the vaccine. It’s not clear what causes the allergic reaction, and the FDA and US Centers for Disease Control and Prevention are investigating.
Moderna’s vaccine is also based on mRNA. “mRNA is like software for the cell,” Moderna said on its website. And like the Pfizer/BioNTech vaccine, it codes for cells to make a piece of the spike protein.
The Moderna vaccine also goes into the muscle cells of the arm, and perhaps to nearby immune system cells, and instructs them to make pieces of spike protein.
Clinical trials showed Moderna’s vaccine was 94% effective in preventing symptomatic infections and the company says it has data showing the vaccine also prevents all infections, including those that do not cause symptoms. Moderna thinks its vaccine will protect against the coronavirus for at least a year.
Moderna has come up with a different formulation for the lipid nanoparticles to protect the mRNA in its vaccine. These formulations are corporate secrets, but Moderna thinks its approach is better and said its vaccine can be shipped at minus 20 degrees C (minus 4 degrees F) and can be kept stable for 30 days at 2 degrees to 8 degrees C (36 to 46F), the temperature of a standard home refrigerator.
The FDA authorized Moderna’s vaccine in December. The US government has contracted to purchase 200 million doses of Moderna’s Covid-19 vaccine, and is in talks to purchase another 100 million doses.
Johnson & Johnson’s vaccine arm, Janssen Pharmaceuticals
Janssen’s coronavirus vaccine is a recombinant vector vaccine. It uses a genetically engineered version of adenovirus 26, which can cause the common cold, but the gene tinkering has disabled it. It also delivers the genetic instructions to make a piece of spike protein.
This is one vaccine that has been tested on the market before. The adenovirus 26 vector was used to make the company’s Ebola vaccine, which won market authorization from the European Commission in July.
It’s the only vaccine tested as a single shot — a significant advantage in a world complicated by the need to ensure people get two carefully spaced doses of vaccine. Plus, it can be stored at normal refrigerator temperatures.
Preliminary data released last week showed the vaccine was 66% effective in preventing moderate and severe disease in a global Phase 3 trial, but 72% effective in the US trial. Plus, it was 85% effective in preventing severe disease, and almost completely effective in preventing death.
“A vaccine that’s inexpensive, that’s a single dose, and that has no cold chain requirements — that’s pretty good,” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told CNN.
Johnson & Johnson is expected to apply for emergency use authorization this week. The company said expects to supply 100 million vaccine doses to the US government in the first half of 2021.
The company is also testing a two-dose regimen in volunteers to see if adding a second dose gives better or longer-lasting protection.
AstraZeneca’s vaccine, made with a team at Britain’s University of Oxford, is, like Janssen’s, a vector vaccine. It uses an adenovirus that infects chimpanzees, but doesn’t make people sick, to carry the spike protein from the coronavirus into cells.
It was modified so that it doesn’t replicate itself, then genetically engineered to inject cells with the DNA encoding for the full coronavirus spike protein.
It’s a cheaper way to make vaccines — but slower than using RNA. The company has pledged to make its vaccine available inexpensively to countries around the world. The vaccine can be kept stable for six months at standard refrigerator temperatures, the company said.
It’s approved in Britain but the US FDA is waiting for data from US trials.
Data released from trials in Britain, South Africa and Brazil in a Lancet preprint Tuesday indicated it’s about 67% effective at preventing symptomatic infection two weeks after two doses. But the Oxford team also tested some volunteers to see if they became infected at all, and said they think the vaccine prevents infections in general.
Plus, the studies indicated a single dose of vaccine prevented 76% of symptomatic infections for up to 90 days, and if more time passed between the first and second doses, the efficacy improved. When volunteers waited 12 weeks between doses, the vaccine’s efficacy went up to 82%. A longer wait between doses would help get more people vaccinated, since the companies are struggling to keep up with demand.
Maryland-based biotechnology company Novavax specializes in “protein subunit” vaccines. They use virus-like nanoparticles as a base and cover them with genetically engineered pieces of the coronavirus spike protein.
This is also a tried and true vaccine approach. A hepatitis B vaccine given to newborns is a protein subunit vaccine, as is the human papillomavirus or HPV vaccine and FluBlok, Sanofi’s influenza vaccine.
Novavax uses an insect virus called a baculovirus to get the coronavirus spike protein into moth cells, which then produce the protein. This is harvested and mixed with an adjuvant — an immune booster –based on saponin, found in soap bark trees.
A Phase 3 trial conducted in the UK showed the vaccine had an efficacy of 89%, the company said last week. It has not published any data yet, but announced results in a news release. The vaccine was found to have 95.6% efficacy against the original novel coronavirus and 85.6% against the variant first identified in the UK, known as B.1.1.7.
And a Phase 2b study conducted in South Africa indicated the vaccine was 60% effective against a variant circulating there and known as B.1.351 — although efficacy went down if HIV-positive volunteers were included.
Sanofi and GlaxoSmithKline
This is also a protein subunit vaccine, using Sanofi’s FluBlok technology with a GlaxoSmithKline adjuvant. It also uses a baculovirus to grow little bits of spike protein.
Phase 1/2 trials showed the vaccine elicits an immune response in younger adults that’s comparable to patients who recovered from Covid-19, but the vaccine did not produce the desired immune response in older adults. The companies plan to launch a new trial in February.
Sinovac and Sinopharm
Chinese company Sinovac’s CoronaVac uses an inactivated virus — one of the oldest methods for vaccinating people. Whole batches of coronavirus are grown, “killed” and then made into vaccine. Likewise, Sinopharm’s vaccine uses an inactivated virus.
China’s Center for Disease Control said this week that tests showed the Sinopharm vaccine was effective against the B.1.351 variant.
Russian researchers were heavily criticized for rolling out the Sputnik V coronavirus vaccine last year without providing any data to show it was safe or effective.
On Tuesday, interim data from a Phase 3 trial were finally published in the Lancet medical journal and showed the vaccine is 91.6% effective at preventing symptomatic Covid-19 and 100% effective for preventing severe illness.
The vaccine is a two-dose adenoviral vector vaccine, with doses administered 21 days apart. It uses two common cold viruses called adenovirus 5 and adenovirus 26 to carry the genetic material for the spike protein into the body.