Scientists are trying a new question about the Covid-19 vaccine: mixing different doses

The search for ways to strengthen the body’s defenses has gained new urgency after the emergence of variants of the virus, the vulnerability of which to existing features is not fully understood.

The researchers said the mix-and-match approach, if validated in human trials, will offer another advantage as countries compete to inoculate their citizens: it could help ease the pressure on the supply of vaccines by donating to doctors more options when patients have a second dose.

“Knowing that different types of vaccines could be mixed depending on supply availability could only accelerate vaccination efforts,” said Helen Fletcher, a professor of immunology at the London School of Hygiene and Tropical Medicine.

Oxford University researchers are enrolling volunteers in a trial of 820 people in the UK to evaluate a combination of two shooting plans developed by Pfizer Inc.

and the German BioNTech BNTX 2.84%

SE and the vaccine developed by Oxford University and AstraZeneca PLC. The trial, funded in part by the UK government, was announced on Thursday by the UK Department of Health and Social Care.

AstraZeneca said in December that it plans to test its vaccine with Sputnik V, the vaccine developed in Russia, in a trial with humans. This trial is expected to begin soon in Azerbaijan, the United Arab Emirates and other countries.

Immunologists said the mix-and-match strategy is a proven method to improve the body’s immune response to recover invaders. First-rate heterologous vaccination has been developed against other infectious diseases, such as Ebola, malaria, and tuberculosis, and has been used to exacerbate the body’s assault on pathogens that cause some cancers and on tumors themselves. .

“I don’t see any disadvantage in the first heterologous impulse,” said Brian Lichty, an associate professor of pathology and molecular medicine at McMaster University in Hamilton, Ontario.

By combining traits that can train the immune system to recognize and attack a pathogen in subtly different ways, the body could gather a larger or better-equipped army to defeat the invaders it encounters, according to researchers. The combination strategy can avoid the risk with a traditional two-shot vaccine that the immune system repels the second time.

Russia’s Sputnik V follows the idea of ​​combining-combining by using a different viral carrier to train the immune system against Covid-19 in each of its doses.

The UK trial will be the first to test against Covid-19 a mix-match approach that uses different technologies. The Pfizer and BioNTech vaccine relies on molecular messengers known as messenger RNA to transmit instructions to cells. AstraZeneca’s uses a modified chimpanzee virus as a vector to supply its payload.

“We don’t have clinical data for this approach,” said Ugur Sahin, CEO of BioNTech. “Therefore, it is important to evaluate the combination of different vaccines within controlled clinical trials before simply applying it in practice.”

Pfizer said in a statement that it recommends using its vaccine in the way it is based on existing test data, but added that decisions on alternative dosing schedules are up to health authorities. AstraZeneca said it supports the trials.

Immunologists said the combinations of technologies are not unusual. Scientists at Oxford University in January reported in a study that they expected revision that the combination of a different RNA-based vaccine and a viral vector vaccine generated a strong immune response in mice. Messenger RNA vaccines have been tested in conjunction with viral virus vaccines in cancer types.

The aim of the trial in the UK is to see if a mix-match approach works as well as better than typical practice, said Matthew Snape, associate professor of paediatrics and vaccinology at Oxford and leader of the process.

Some participants will get a shot from AstraZeneca first and a second from Pfizer. Others will achieve the opposite. Control groups will be given the normal schedule of two shots of a single vaccine. The trial will also examine the distance between the shots for four to twelve weeks. Preliminary results are expected in late May or early June and participants ’side effects will be closely monitored. The plan is to enroll more volunteers and test new combinations as additional vaccines get regulatory approval in the UK, Professor Snape said.

Researchers will regularly test participants ’blood for antibodies, infection-fighting T cells, and other markers of immune system activity. They will compare those in the mixed program with those in the normal dosing regimen to detect any differences. Professor Snape said researchers will be able to use these samples to assess the potential effectiveness of a combined vaccine against coronavirus variants that may not be as vulnerable to standard shots.

Mary Ramsay, head of immunization at Public Health England, a UK health agency, said success in the trial could help doctors dealing with bottlenecks in delivering vaccines. A combination and help strategy could help if, for example, someone did not get a second dose of the original shot or experienced a bad reaction to the first.

“It really makes implementation a lot easier,” he said.

Mene Pangalos, AstraZeneca’s executive vice president for biopharmaceutical research and development, said at a news conference on Wednesday: “Ultimately, we want to understand how these vaccines are interchangeable. These are important questions, because ultimately, people will use different vaccines at different times ”.

—Jenny Strasburg and Bojan Pancevski contributed to this article.

Write to Jason Douglas to [email protected]