How the Gamaleya Sputnik V vaccine works

The Gamaleya Research Institute, part of the Russian Ministry of Health, developed a vaccine against the coronavirus known as 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 Coronavirus

The SARS-CoV-2 virus is full of proteins that it uses to enter human cells. These proteins called pico are a tempting target for vaccines and potential treatments.

Sputnik V is based on the virus’s genetic instructions for building the spike protein. But unlike the Pfizer-BioNTech and Moderna vaccines, which store instructions in single-stranded RNA, Sputnik V uses double-stranded DNA.

DNA inside adenovirus

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

Sputnik V emerges from decades of research with 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 based on adenovirus, such as one from Johnson & Johnson using Ad26 and one from the University of Oxford and AstraZeneca using a chimpanzee adenovirus.

Entering a Cell

After Sputnik V is injected into a person’s arm, adenoviruses collide with cells and attach themselves to proteins on their surface. The cell wraps the virus in a bubble and pulls it inside. Once inside, the adenovirus escapes from the bubble and travels 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 spike protein can be read by the cell and copied into a molecule called messenger RNA, or mRNA.

Peak protein creation

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

Some of the spike proteins produced by the cell form spines that migrate to its surface and project its tips. The vaccinated cells also break some of the proteins into fragments, which they present on their surface. These protruding tips and fragments of cutting-edge proteins can then be recognized by the immune system.

Adenovirus also triggers the immune system by turning on cell alarm systems. The cell sends warning signals to activate nearby immune cells. By triggering this alarm, Sputnik V causes the immune system to react more strongly to peak proteins.

Spotting the Intruder

When a vaccinated cell dies, the fragments contain peak proteins and protein fragments that can be absorbed by a type of immune cell called an antigen-presenting cell.

The cell has fragments of the spike protein on its surface. When other cells called helper T cells detect these fragments, helper T cells can sound the alarm and help organize other cells in the immune system to fight infection.

Making Antibodies

Other cells of the immune system, called B cells, can collide with the spikes of the coronavirus on the surface of the vaccinated cells, or fragments of proteins with floating spikes. Some of the B cells may be able to lock on the peak proteins. If these B cells are activated by helper T cells, they will begin to proliferate and release antibodies that target the spike protein.

Stopping the virus

Antibodies can attach to the coronavirus peaks, mark the virus for destruction and prevent infection, preventing the peaks from attaching to other cells.

Killing infected cells

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 display peak protein fragments on their surfaces.

Two doses

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

Covid-19 adenovirus-based vaccines are more resistant than Pfizer and Moderna mRNA vaccines. DNA is not as fragile as RNA, and the adenovirus resistant protein coating helps to protect internal genetic material. As a result, Sputnik V can be refrigerated and does not require very low storage temperatures.

Remembering the virus

Gamaleya announced that Sputnik V has an effectiveness rate of 91.4%, but has not yet published a scientific article with all the details of the test.

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

Vaccines Timeline

June 2020 Gamaleya launches clinical trials of his vaccine, initially called Gam-Covid-Vac.

August 11th President Vladimir V. Putin announces that a Russian health regulator has approved the vaccine, renamed Sputnik V, even before Phase 3 testing has begun. Vaccine experts consider the move risky.

August 20th Russia goes back on its previous announcement, saying the vaccine approval was a “certificate of conditional registration” that depends on the positive results of the Phase 3 tests.

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

September 7 A Phase 3 test begins in Russia.

October 17 A 2/3 phase test is launched in India.

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

November The Russian government begins to offer Sputnik V in Russia in a mass vaccination campaign. But the concern that the vaccine was hastily approved leads to widespread hesitation in the country.

December The Phase 3 trial reaches its final total of 78 cases. The effectiveness rate remained effectively unchanged, at 91.4 percent. Of the 78 cases of Covid-19 in the trial, 20 were severe – and all 20 were in volunteers who received the placebo. In addition, the researchers announced that they found no serious side effects with the vaccine.

December 11 Gamaleya joins forces with the pharmaceutical company AstraZeneca, which is also developing a vaccine based on adenovirus. 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 giving up on receiving the vaccine now that it is widely available. The researchers who carried out the trial reduced the planned size from 40,000 to 31,000 participants, causing experts to worry that they would not have enough statistical power to reach solid 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 authorizes the vaccine for emergency use.

December, 24 AstraZeneca registers a Phase 1 study for a combination of the Sputnik V and Oxford-AstraZeneca vaccines.

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

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