AstraZeneca will begin clinical trials in December on a combination regimen that includes their own COVID-19 vaccine candidate and part of Russia’s Sputnik V. The UK-based pharma announced it would explore combinations of different types of vaccines following phase 3 data published in The Lancet showing its own vaccine yielded lower efficacy than that achieved by mRNA vaccines from Moderna and Pfizer/BioNTech. The US Food and Drug Administration granted Emergency Use Authorization for the Pfizer/BioNTech vaccine on 11 December and for the Moderna vaccine on 18 December.

Russia’s Sputnik V vaccine was developed by the Gamaleya Research Institute and backed by the sovereign Russian Direct Investment Fund. It received a controversial approval from the Russian government in August before phase 3 efficacy trials had begun. The vaccine, which follows a prime-and-boost approach, combines two slightly different human adenovirus-based vectors: a recombinant adenovirus serotype 26 (Ad26) and serotype 5 (Ad5). Each bears genetic fragments that encode the SARS-CoV-2 spike glycoprotein. Interim results announced on 14 December show Sputnik V with an efficacy of 91.4% in phase 3 trials, but data have not yet been published.

Also in December, AstraZeneca and University of Oxford reported preliminary data from a phase 3 trial of their vaccine candidate, AZD1222. The vaccine showed 70.4% efficacy overall after two doses. But the company also revealed a puzzling finding: a subpopulation receiving a lower first dose, due to an error in dosing, experienced 90% efficacy.

AZD1222 uses the chimpanzee ChAdOx1 adenovirus vector to express the spike protein. AstraZeneca will test its own vaccine with Gamaleya’s Ad26 vector. Some experts have warned that the other vector used by Gamaleya, Ad5, is derived from a human cold virus, which means some people may have a pre-existing immunity that could hamper response to the COVID-19 spike protein.