How Gamaleya’s Sputnik V Vaccine Works

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

A piece of the coronavirus

The SARS-CoV-2 virus is littered with proteins that it uses to enter human cells. These so-called vein proteins are an attractive target for potential vaccines and treatments.

Sputnik V is based on the virus’ genetic instructions to build the ear protein. But unlike the Pfizer-BioNTech and Moderna vaccines, which preserve the instructions in single-stranded RNA, Sputnik V uses double-stranded DNA.

DNA are adenoviruses

The researchers developed their vaccine from adenoviruses, a type of virus that causes colds. They added the gene for the coronavirus proteins to two types of adenovirus, one called Ad26 and one called Ad5, and designed it so that they could invade cells but not repeat.

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

Enter a cell

After Sputnik V is injected into the person’s arm, the adenoviruses strike cells and cling to proteins on their surface. The cell swallows the virus in a bubble and pulls it inside. The adenovirus escapes from the bubble and moves to the nucleus, the chamber where the cell’s DNA is stored.

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 ear protein can be read by the cell and copied into a molecule called messenger RNA, or mRNA.

Build vein proteins

The mRNA leaves the nucleus, and the cell’s molecules read its sequence and begin assembling proteins.

Some of the vein proteins produced by the cell form nails that migrate to the surface and protrude their tips. The grafted cells also break down some of the proteins into fragments that provide them on their surface. These protruding spikes and peak protein fragments can then be recognized by the immune system.

The adenovirus also triggers the immune system by activating the cell’s alarm systems. The cell sends out warning signals to activate immune cells in the environment. By triggering this alarm, Sputnik V causes the immune system to respond more strongly to the peak proteins.

See the intruder

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

The cell presents fragments of the vein protein on the surface. When other cells called helper T cells detect these fragments, the helper T cells can sound the alarm and help other immune cells fight the infection.

Make antibodies

Other immune cells, called B cells, can bump into the surface of vaccinated cells in the coronavirus nails or free-floating vein protein fragments. Some of the B cells may be attached to the vein proteins. If these B cells are then activated by helper T cells, they will multiply and secrete antibodies that focus on the protein.

Stop the virus

The antibodies can cling to the coronavirus nails, marking the virus for destruction and preventing infection from attaching the nails to other cells.

Killing infected cells

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

Two doses

Some researchers are concerned that our immune systems may respond to an adenovirus vaccine by making antibodies against it, which would render 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 dose.

Adenovirus-based vaccines for Covid-19 are more robust than the mRNA vaccines from Pfizer and Moderna. DNA is not as fragile as RNA, and the adenovirus’s sticky protein layer helps protect the genetic material inside. As a result, Sputnik V may be in the refrigerator and does not require very low storage temperatures.

Remember the virus

Gamaleya announced that Sputnik V has an efficiency rate of 91.4 percent, but has not yet published a scientific article with the full details of the trial.

It is not yet clear how long the protection of the vaccine can last. The level of antibodies and killer T cells caused by the vaccine can drop during the months after vaccination. But the immune system also contains special cells, memory B cells, and memory T cells that can retain information about the coronavirus for years or even decades.

Vaccination timeline

June 2020 Gamaleya is launching clinical trials with their vaccine, initially called Gam-Covid-Vac.

August 11 President Vladimir V. Putin announces that a Russian health regulator has approved the vaccine, renamed Sputnik V, before phase 3 trials even begin. Vaccination experts consider the move risky.

August 20 Russia steps back with its earlier announcement, saying the vaccine’s approval is a “conditional registration certificate” that depends on positive results from Phase 3 trials.

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

September 7 A Phase 3 trial is set to begin in Russia.

October 17 A Phase 2/3 trial is launched in India.

11 November The Russian Direct Investment Fund announces the first preliminary evidence from their Phase 3 trial indicating that the vaccine is effective. Based on 20 cases of Covid-19 among the participants in the trial, Russian scientists estimate that the vaccine is 92 percent effective.

November The Russian government begins hosting Sputnik V inside Russia in a mass vaccination campaign. But worrying that the vaccine was rushed after approval is leading to widespread hesitation in the country.

December The Phase 3 trial reaches its final total of 78 cases. The efficiency rate was effectively unchanged, at 91.4 percent. Of the 78 cases of Covid-19 in the trial, 20 were serious – and all 20 were in volunteers who received the placebo. In addition, the researchers announce that they have not found any serious side effects of the vaccine.

December 11 Gamaleya is teaming up with drugmaker AstraZeneca, which is also developing an adenovirus-based vaccine. The two teams will combine their vaccines to see if they provide stronger protection together.

December 24 The Associated Press reports that trial volunteers who suspect they have received the placebo are dropping out to receive the vaccine now that it is widely available. The researchers conducting the trial reduce the planned size from 40,000 to 31,000 participants, causing experts to worry that they will not have enough statistical power to draw strong conclusions about the safety and efficacy of the vaccine.

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

December 23 Argentina authorize the vaccine for emergency use.

December 24 AstraZeneca is registering a Phase 1 trial for a combination of the Sputnik V and Oxford AstraZeneca vaccines.

Additional reporting by Yuliya Parshina-Kottas. Sources: National Center for Biotechnology Information; Earth; Lynda Coughlan, University of Maryland School of Medicine.

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