Mix-and-match COVID vaccines trigger potent immune response

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Preliminary results from a trial of more than 600 people are the first to show the benefits of combining different vaccines.

Empty vials of COVID-19 vaccines.
Countries with fluctuating supplies of COVID-19 vaccines could benefit from using different vaccines for the first and second dose.Credit: Christof Stache/AFP/Getty

According to researchers performing a study in Spain, both the Oxford–AstraZeneca and Pfizer–BioNTech COVID-19 vaccines produce a robust immune response against the virus SARS-CoV-2. The benefits of mixing multiple coronavirus vaccines are the first to be shown, according to preliminary data from a trial of more than 600 people, which were disclosed in an online presentation on May 181. Last week, a UK trial using a similar technique reported2 safety data, and further information on immune responses is due soon. Several European governments are already suggesting that some or all persons who received a first dosage of the vaccine developed by the University of Oxford and AstraZeneca in Cambridge, UK, receive a second dose of the vaccine due to safety concerns. Researchers expect that mixing and matching COVID-19 vaccine regimens would result in greater, more robust immune responses than two doses of a single vaccine, while also simplifying immunisation efforts for nations with erratic vaccine supplies.

Prime and boost

The Spanish CombivacS trial, which began in April, involved 663 people who had already received a first dose of the Oxford–AstraZeneca vaccine, which employs a harmless chimpanzee ‘adenovirus’ to transmit instructions for cells to create SARS-CoV-2 protein. At least eight weeks after their first dose, two-thirds of the patients were chosen at random to get the mRNA-based vaccination developed by Pfizer, based in New York City, and BioNTech, based in Mainz, Germany. A 232-person control group has yet to get a booster. The Carlos III Health Institute in Madrid led the research. According to Magdalena Campins, a CombivacS research investigator at the Vall d’Hebron University Hospital in Barcelona, Spain, the Pfizer–BioNTech booster seemed to startle the immune systems of the Oxford–AstraZeneca-dosed patients. Participants produced substantially larger amounts of antibodies after the second dosage, and these antibodies were able to detect and inactivate SARS-CoV-2 in laboratory tests. There was no difference in antibody levels in control subjects who did not receive a booster immunisation. That is what researchers hoped and expected from combining multiple vaccinations, an approach known as a heterologous prime and boost, which has been used to develop vaccines for other diseases like Ebola. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, Massachusetts, says, “These responses look promising and highlight the promise of heterologous prime–boost regimens.” According to Altmann, giving patients alternative vaccines for the first and second doses is probably a good idea. However, he is concerned about what will happen if a third dose is required to maintain immunity or protect against new coronavirus strains. Because the immune system generates a response against the adenovirus, repeated doses of virus-based vaccinations, such as the Oxford–AstraZeneca vaccine, become gradually less effective. With increased doses, RNA vaccines, on the other hand, tend to cause more serious adverse effects. “I believe there is a beautiful new world of vaccination to be explored in all of this,” adds Altmann.

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