How Gamaleya’s Sputnik V Vaccine Works

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How Gamaleya’s Sputnik V Vaccine Works

The Gamaleya Research Institute, part of the Russian Ministry of Health, developed a coronavirus vaccine called Sputnik V. or Gam-Covid-Vac. Gamaleya announced in December that the vaccine was 91.4 percent effective. Russia is using it in a mass vaccination campaign and is now being distributed in Argentina, Belarus and other countries.

A piece of the coronavirus

The SARS-CoV-2 virus is filled with proteins that it uses to enter human cells. These so-called spike proteins are a tempting target for potential vaccines and treatments.

Sputnik V is based on the virus' genetic instructions for building the spike protein. In contrast to the Pfizer-BioNTech and Moderna vaccines, in which the instructions are stored in single-stranded RNA, Sputnik V uses double-stranded DNA.

DNA in adenoviruses

The researchers developed their vaccine from adenoviruses, a type of virus that causes colds. They added the gene for the coronavirus spike protein gene to two types of adenoviruses, one called Ad26 and one called Ad5, and engineered them so they could enter cells but not replicate.

Sputnik V comes from decades of research into adenovirus-based vaccines. The first was approved for general use last year – an Ebola vaccine made by Johnson & Johnson. Some other coronavirus vaccines are also adenovirus-based, like one from Johnson & Johnson using Ad26 and one from the University of Oxford and AstraZeneca using a chimpanzee adenovirus.

Enter a cell

After Sputnik V is injected into a person's arm, the adenoviruses bump into cells and cling to proteins on their surface. The cell swallows the virus into a bubble and pulls it inside. Inside, the adenovirus escapes from the bladder and migrates to the nucleus, the chamber in which the cell's DNA is stored.

Virus devoured

in a bubble

Virus devoured

in a bubble

Virus devoured

in a bubble

The adenovirus pushes its DNA into the nucleus. The adenovirus is designed so that it cannot make copies of itself, but the gene for the coronavirus spike protein can be read by the cell and copied into a molecule called messenger RNA or mRNA.

Structure of spike proteins

The mRNA leaves the nucleus and the cell's molecules read their sequence and start building spike proteins.

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Some of the spike proteins produced by the cell form spikes that migrate to its surface and their tips stick out. The vaccinated cells also break down into fragments some of the proteins that they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system.

The adenovirus also provokes the immune system by turning on the cell's alarm systems. The cell sends out warning signals to activate nearby immune cells. By triggering this alarm, Sputnik V causes the immune system to react more strongly to the spike proteins.

Discover the intruder

When a vaccinated cell dies, the debris contains spike proteins and protein fragments, which can then be taken up by a type of immune cell called an antigen-presenting cell.

Present a

Spike protein

fragment

Present a

Spike protein

fragment

Present a

Spike protein

fragment

The cell presents fragments of the spike protein on its surface. When other cells called helper T cells recognize these fragments, the helper T cells can set off the alarm and help other immune cells fight the infection.

Make antibodies

Other immune cells, called B cells, can bump against the coronavirus spikes on the surface of vaccinated cells or against free-floating spike protein fragments. Some of the B cells may be able to bind to the spike proteins. When these B cells are then activated by helper T cells, they begin to multiply and pour out antibodies that target the spike protein.

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

surface

Proteins

Matching

surface

Proteins

Matching

surface

Proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Stop the virus

The antibodies can attach to coronavirus spikes, mark the virus for destruction, and prevent infection by preventing the spikes from attaching to other cells.

Kill infected cells

The antigen presenting cells can also activate another type of immune cell called a killer T cell to search for and destroy any coronavirus infected cells that have the spike protein fragments on their surfaces.

Present a

Spike protein

fragment

Beginning

to kill them

infected cell

Present a

Spike protein

fragment

Beginning

to kill them

infected cell

Present a

Spike protein

fragment

Beginning

to kill them

infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Two cans

Some researchers fear that our immune systems may respond to an adenovirus vaccine by making antibodies against it, rendering a second dose ineffective. To avoid this, the Russian researchers used one type of adenovirus, Ad26, for the first dose and another, Ad5, for the second.

Second dose

21 days later:

Ad5

Second dose

21 days later: Ad5

Second dose

21 days later: Ad5

Adenovirus-based vaccines against Covid-19 are more robust than Pfizer and Moderna mRNA vaccines. DNA isn't as fragile as RNA, and the adenovirus' hard protein shell protects the genetic material inside. As a result, Sputnik V can be refrigerated and does not require very low storage temperatures.

Memory of the virus

Gamaleya has announced that Sputnik V has an effectiveness rate of 91.4 percent but has not yet published a scientific paper with the full details of the study.

Two color-coded cans from Sputnik V.Russian direct investment fund through EPA

It is not yet clear how long the vaccine could take to protect. The levels of antibodies and killer T cells produced by the vaccine may decrease in the months following vaccination. However, the immune system also contains special cells called storage B cells and storage T cells that can store information about the coronavirus for years or even decades.

Vaccination timeline

June 2020 Gamaleya is starting clinical trials with its vaccine, originally called Gam-Covid-Vac.

August 11th President Vladimir V. Putin announced that a Russian health agency had approved the vaccine, which was renamed Sputnik V, prior to the start of phase 3 trials. Vaccine experts describe the move as risky.

20th of August Russia is stepping back on its earlier announcement, saying the vaccine approval is a "conditional certificate of registration" that is dependent on positive results from phase 3 trials.

Russia's President Vladimir Putin during a conference call on Aug. 11.Alexei Nikolsky / EPA

September 4th Gamaleya researchers publish the results of their phase 1/2 study. In a small study, they found that Sputnik V produced antibodies against the coronavirus and mild side effects.

7th of September A phase 3 study is starting in Russia.

October 17th A phase 2/3 study is being started in India.

November 11th The Russian Direct Investment Fund is releasing the first preliminary evidence from its Phase 3 study, suggesting the vaccine is effective. Based on 20 cases of Covid-19 among the study participants, Russian scientists estimate that the vaccine has an effectiveness of 92 percent.

A vial of Gamaleya's vaccine.Fedja Grulovic / Reuters

November The Russian government is offering Sputnik V in Russia as part of a mass vaccination campaign. However, concerns that the vaccine has been approved is creating widespread reluctance in the country.

December The phase 3 study reaches its final total of 78 cases. The effectiveness rate remained practically unchanged at 91.4 percent. Of the 78 cases of Covid-19 in the study, 20 were serious – and all 20 were volunteers who received the placebo. In addition, the researchers announce that they did not see any serious side effects from the vaccine.

11th December Gamaleya partners with drug maker AstraZeneca, which is also developing an adenovirus-based vaccine. The two teams will combine their vaccines to see if they offer stronger protection together.

Vials of the vaccine in a facility near Saint Petersburg, Russia.Anton Vaganov / Reuters

24th of December The Associated Press reports that volunteer subjects who suspect they received the placebo discontinued the vaccine once it became widely available. The researchers conducting the study are reducing the planned size from 40,000 to 31,000 participants, leading experts to fear that the statistical power is insufficient to draw firm conclusions about the safety and effectiveness of the vaccine.

December 22 Belarus is the first country outside of Russia to register Sputnik V.

23rd of December Argentina approves the emergency vaccine.

Vials of the vaccine in Rosario, Argentina.Agence France-Press

24th of December AstraZeneca is registering a phase 1 study for a combination of the vaccines Sputnik V and Oxford-AstraZeneca.

Preparation of a dose in Moscow on December 30th.Natalia Kolesnikova / Agence France-Presse


Additional reporting from Yuliya Parshina-Kottas. Sources: National Center for Information on Biotechnology; Nature; Lynda Coughlan, University of Maryland Medical School.

Chasing the coronavirus

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