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How leading COVID-19 vaccines work

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covid-19 vaccine, vaccine, covid-19

If they’re positive, the company plans to apply for emergency use authorization from the US Food and Drug Administration and make the vaccine available to the public.

Two vaccines already have FDA and European authorization and three are authorized in the UK. Here’s how some of the top coronavirus vaccines 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 — the structure that adorns the surface of the coronavirus, giving it that studded appearance.

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 the particular piece of the virus’s spike protein. 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.

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 F (minus 75 degrees C). 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 200 million doses of Pfizer’s coronavirus vaccine.

Side-effects 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

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. That was a careful choice — scientists had to pick a piece of the virus they thought would not mutate, or change much, as time passed. The virus uses the spike protein to grapple the cells it attacks and the structure does appear to stay stable through generation after generation of viral replication.

Like Pfizer’s vaccine, the Moderna vaccine 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 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 and the US has contracted for 200 million doses of Moderna’s vaccine.

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 marketing authorization from the European Commission in July.

It’s a one-shot vaccine. Phase 1-2 trial data published in the New England Journal of Medicine this week show the vaccine generated an antibody response in volunteers aged 18 to 55 as well as a second batch of volunteers 65 and older. Side-effects were minimal.

The company is also testing a two-dose regimen in volunteers to see if adding a second dose gives better protection or longer-lasting protection.

AstraZeneca

AstraZeneca’s vaccine, made with a team at Britain’s Oxford University, is called a vector vaccine. It uses a common cold virus called an adenovirus to carry the spike protein from the coronavirus into cells.

It also aims to make people’s bodies produce their own vaccines by churning out little copies of spike protein, but the delivery method is different. This adenovirus infects chimpanzees but doesn’t make people sick. 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. Confusing data from trials indicated AstraZeneca’s vaccine could be 70% effective on average.

Novavax

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.

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 comparable to patients who recovered from Covid-19 in younger adults, 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 in an inactivated virus.

Sputnik V

Russia’s Sputnik V coronavirus vaccine is an adenoviral vector vaccine. It uses two common cold viruses called adenovirus 5 and adenovirus 26 to carry the genetic material for the spike protein into the body.

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