Sputnik V, Russia’s adenovirus-based vaccine against COVID-19, was a coup for Russian biomedicine when it was brought to market in late 2020. Used on an emergency basis by over 70 countries, hundreds of millions of people were soon given a first dose of the vaccine, which comprises recombinant Ad26 (encoding the coronavirus spike protein), followed by a second, heterologous dose of an Ad5-based vector. Cheaper than its US, European and Chinese competitors, and validated in an April 2021 Lancet study, Sputnik V catapulted Russian biomedical research far aloft — much as the Sputnik satellite did for Russian space scientists almost 65 years ago.

But the vaccine’s early use in many nations across the world may have been compromised by Russia’s invasion of Ukraine on 24 February 2022, which suddenly eclipsed Sputnik’s future commercial prospects.

Fortunately, research from Argentina published in Lancet Regional Health Americas on 24 January indicates that countries that now face Sputnik V supply problems can safely use alternative vaccines for second doses.

“The message for countries that may find themselves in a similar situation to Argentina is clear,” says Alejandro Macchia, an epidemiologist who works for the Ministry of Health of the City of Buenos Aires and is a member of the Grupo de Estudio sobre Investigación Clínica en Argentina. “The second component of the Sputnik V vaccine can be replaced using RNA technology vaccines and to a lesser extent using AstraZeneca's vaccine.”

Fernán Quirós, Minister of Health for the City of Buenos Aires, agrees with Macchia. “The city's clinical trials established that the use of RNA vaccines was sufficiently safe and efficacious for them to be exchanged, and vaccine exchange became standard practice,” Quirós tells Nature Medicine.

These assurances may be welcome news to health officials in scores of countries where the severity of Sputnik V’s supply constraints are now sinking in.

On 28 February, The US Department of the Treasury’s Office of Foreign Assets Control placed Sputnik V’s developer, the Russian Direct Investment Fund (RDIF), and its chief executive, Kirill Dmitriev, on its list of sanctioned Russian entities and people. The European Union followed, with sanctions against RDIF from 12 March.

“While officially a sovereign wealth fund, RDIF is widely considered a slush fund for President Vladmimir Putin and is emblematic of Russia’s wider kleptocracy,” a statement from the US Department of the Treasury explained. Andrew Leach, a partner with London-based Hudson Sandler, a communications firm with a Moscow office that until 24 February helped handle media inquiries for RDIF, says the company “no longer works with RDIF — or indeed any Russian clients.”

At RDIF in Moscow, Alexey Urazov, Director for External Communications, did not respond to emails requesting interviews, and RDIF’s website is now inaccessible. In a statement reported by TASS, a Russian government news service, RDIF said it “was never involved in any political activities,” was not involved in interacting with Ukraine, and follows the world’s best investment practices. TASS added that RDIF warned “the restrictions could ultimately deprive billions of people around the world of access to safe and efficient vaccines made in Russia.”

At the Gamaleya National Research Centre of Epidemiology and Microbiology in Moscow, Denis Logunov, who is the corresponding author on the 2021 Lancet study that first validated Sputnik, did not respond to emailed interview requests. Nor did Gameleya’s director, Alexander Gintsburg.

In Buenos Aires, Macchia says Argentina’s awkward tango with Sputnik started with a decision in late 2020 by the federal government to exclusively use Sputnik, rather than taking a more pluralistic approach that included other vaccines.

The national government's decision to rely exclusively on the availability of the Sputnik vaccine proved to be wrong,” Macchia says bluntly. Indeed, Russia proved unable to deliver the second, Ad5-based dose of its two-part vaccine in mid-2021, before the 2022 invasion of Ukraine, but after two thirds of Argentinians had received a first shot.

“Russian producers were unable to deliver as agreed and this put at risk a large number of people who were expecting to complete the vaccination schedule,” says Macchia, with production problems in Russia blamed for delays.

But Macchia also blames the lack of availability of other vaccines in 2021. “The stockpiling of vaccines by G7 countries in overabundant quantities is also responsible for this risk to which many populations are exposed.”

In August 2021, there were 170,000 people in the city of Buenos Aires waiting for a second dose of Sputnik V. A potential solution to the crisis came when the US government donated more than 3 million Moderna vaccines to Argentina in the summer of 2021.

But no trial evidence existed to validate mixing Sputnik with Moderna, a fact that Macchia ascribes to the research divide between rich countries and middle- and low-income countries.

“There are clinical trials that tested the safety and immunogenicity of combining adenoviral vector–based vaccines with RNA vaccines, for example, Astra Zeneca with Pfizer, but none with Sputnik” says Macchia.

In St. Petersburg, Russia, Sputnik researcher Anton Barchuk, head of the Institute for Interdisciplinary Health Research at the European University at St. Petersburg, also says he is unaware of previous studies in which first shots of Sputnik were followed by other vaccines. “It is unlikely that there are many individuals who got something else after Sputnik in Russia,” Barchuk said in an email on 8 March 2022.

The lack of data on heterologous vaccination with Sputnik may stem in part from the vaccine’s not yet being approved by the World Health Organization (WHO).

“WHO has not issued any policy recommendations for the use of Sputnik V COVID-19 vaccine, including for its heterologous use,” said Margaret Harris, a Geneva-based WHO spokesperson. “Policy formulation for a vaccine is only issued for products that have either the WHO Emergency Use Listing (EUL) or have been authorized for use by a WHO-listed regulatory authority (WLA).”

Now that the safety and efficacy of heterologous vaccines have been shown, Quirós says the first shot of Sputnik can with confidence be followed with second-shot substitutes.

With manufacturing challenges in 2021, and sanctions in 2022, Sputnik’s earthward trajectory seems likely to continue.