AstraZeneca-Sputnik V COVID-19 vaccines prepare for a combined trial

By Rahul Vaimal, Associate Editor
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In collaboration with the Russian Gamaleya Research Institute, the Russian Direct Investment Fund (RDIF) and R-Pharm, UK-based drugmaker AstraZeneca will conduct a clinical trial to test the safety and immunogenicity of the combination of their respective adenovirus-vector vaccines Sputnik V and AZD1222.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human. The trial will begin enrolling adults aged 18 and older, the Russian subsidiary of AstraZeneca said.

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“We welcome the beginning of this new stage of cooperation between vaccine producers. We are determined to develop this partnership in the future and to start joint production after the new vaccine demonstrates its efficacy in the course of clinical trials,” RDIF CEO Kirill Dmitriev said in another statement by the Russian sovereign fund.

While AZD1222 has been developed by British firm AstraZeneca and University of Oxford, Sputnik V has been co-developed by RDIF and Gamaleya.

“Combinations of different COVID-19 vaccines may be an important step in generating wider protection through a stronger immune response and better accessibility. This is why it is important to explore heterologous boosting to make immunization programs more flexible, by allowing physicians greater choice at the time of administering vaccines. It is expected that combining vaccines may lead to improved immune response,” AstraZeneca Russia said in a statement.

Similarity and differences

Both vaccines, AZD1222 and Sputnik V, are double-dose vaccines and both are based on the same adenoviral vector platform, where the virus contains genetic material of COVID-19 causing SARS-CoV-2 virus spike protein. The adenovirus itself is unable to replicate so it can only act as a carrier of genetic material.

The two vaccines, however, have a crucial difference. Although the AstraZeneca vaccine uses chimpanzee adenovirus that does not affect humans, Sputnik V uses two separate strains of human adenovirus in the two doses. The adenovirus is known to cause a mild common cold in humans.

Some Sputnik V researchers speculated that this difference between the two vaccines caused a major difference in the efficacy rates of the two. Although two full doses of a single strain of chimpanzee adenovirus vectors resulted in a 62 percent efficacy rate for the AstraZeneca vaccine, two separate doses of human adenovirus vector vaccine strains resulted in a 92 percent efficacy rate for Sputnik V. Both data are not final.

The theory was that the body became immune to the adenovirus after the first dose, in the case of AZD1222 vaccine, which led to the lower immune efficacy after the second dose, after which RDIF offered AstraZeneca one of its viral vectors for a combination trial.

AstraZeneca is also exploring other combinations of different adenovirus vector vaccines, the statement said.

The UK government also recently announced that it will begin a clinical trial combining the adenovirus vaccines with mRNA technology, which include vaccines from US-based drugmakers Pfizer and Moderna. Pfizer’s mRNA vaccine was recently approved by UK Medicines and Healthcare products Regulatory Agency (MHRA), making the world’s first COVID-19 vaccine to receive regulatory approval.

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