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A trial will test a two-shot vaccine regimen that uses two types of COVID vaccine.Credit: Ben Hasty / MediaNews Group / Reading Eagle / Getty
UK researchers have launched a study that will mix and match two COVID-19 vaccines in an attempt to ease the overwhelming logistics of immunizing millions of people and potentially boost immune responses in the process.
Most coronavirus vaccines are given as two injections: a “main” starting dose followed by a “booster” to stimulate the memory cells of the immune system and amplify the immune response. The clinical trial will test participants’ immune responses by receiving an injection of a coronavirus vaccine produced by Oxford and pharmaceutical company AstraZeneca, which uses a harmless virus to deliver a key coronavirus gene into cells, and an injection of the vaccine produced by the pharmaceutical company Pfizer. , which uses RNA instructions to trigger an immune response. The trial, which is led by researchers at the University of Oxford, aims to begin enrollment on February 4.
Vaccine developers often combine two vaccines to fight the same pathogen, and researchers are eager to implement the strategy, known as a heterologous primary drive, against the coronavirus. Last year, European regulators approved a heterologous primer and boost combination to protect against Ebola, and experimental HIV vaccines are often based on the strategy, says Dan Barouch, director of the Center for Virology and Vaccine Research at the Beth Israel Deaconess Medical Center in Boston. Massachusetts. But it has not yet been tested with vaccines against COVID-19, which are usually given as a repeat injection of the same vaccine.
The ability to combine vaccines could make vaccination programs more flexible: it would speed up the process and reduce the impact of any disruptions in the supply chain. “It really makes implementation a lot simpler,” Mary Ramsay, head of immunization for Public Health England, said at a press conference on February 3.
Oxford has said it will also test combinations of its COVID-19 vaccine with the Russian coronavirus vaccine, Sputnik V, which uses harmless viruses to transport components of the coronavirus into cells. Sputnik V, which this week was shownone To be more than 90% effective against COVID-19, it is itself a heterologous primary booster vaccine, consisting of different viral components in the first and second doses.
T cell approach
Some researchers also think that the combination of two vaccines could strengthen the immune response by taking advantage of the best characteristics of each. That would be particularly desirable now that vaccine developers are fighting coronavirus variants that appear to be partially resistant to certain immune responses, says Barouch. “The responses may be better than any of the vaccines can achieve alone,” says Barouch. “But that remains to be experimentally tested for COVID-19.”
The Oxford trial aims to enroll 820 people and will test two dosing schedules: one with 4 weeks between the two injections and another with a 12-week interval. The test will not directly analyze how well the combination protects against COVID-19; such a study would have to be much larger and time consuming to complete. Instead, the team will take blood samples regularly to measure the levels of antibodies and immune cells called T cells that the participants produce against the coronavirus. You will also monitor security issues.
T cells could be key to stimulating the immune response. RNA vaccines have generated powerful antibody responses to the SARS-CoV-2 coronavirus. But they have not been shown to be as good as the AstraZeneca and Oxford vaccines at stimulating a class of T cells called CD8.+ T cells, says Zhou Xing, an immunologist at McMaster University in Hamilton, Canada. These cells can strengthen an immune response by identifying and destroying cells infected with the virus.
Animal studies suggest that a heightened immune response is possible: in a preprint published in bioRxiv January 292, the researchers reported that a combination of an RNA coronavirus vaccine and the AstraZeneca vaccine aroused CD8+ Better T cells in mice than any single vaccine.
Viral Vectors
Other combinations could produce similar results. Immunologist Jae-Hwan Nam from the Catholic University of Korea in Bucheon is particularly interested in seeing trials of the AstraZeneca vaccine in conjunction with a protein-based vaccine manufactured by Novavax in Gaithersburg, Maryland. Protein vaccines elicit immune responses similar to RNA vaccines, he says, and Novavax’s vaccine may be easier to manufacture and distribute than RNA vaccines.
Unlike RNA vaccines, Sputnik V works by combining two vaccines, each of which places DNA that encodes a crucial coronavirus protein, called a pico, into a harmless virus. The virus enters human cells, where DNA is expressed. The immune system then generates a response to the spike protein.
But if the same virus is used in subsequent injections, an immune response against the harmless virus itself could slow the response to the spike. Sputnik V solves this problem by using two different transport viruses, one in each shot. AstraZeneca’s vaccine uses only one, which makes heterologous primary booster studies with the Pfizer and Sputnik V vaccine particularly attractive.
If all goes well, the results of the test group testing the four-week regimen should be available in June, in time to inform the UK’s ongoing vaccination campaign, says Matthew Snape, a University of Oxford pediatrician and researcher. main test. .
Snape says the team hopes to add more vaccines to their study as they become available. The combined studies are made possible by the rapid development of multiple coronavirus vaccine options, Xing says. “We are in a strong position to seek the best immunologically considered strategies,” he says.
