This evidence synthesis has been compiled by members of the CITF Secretariat and does not necessarily represent the views of all CITF members.

By Mariana Bego

It has been proposed that immunization with different vaccine products for the first and second dose may increase the intensity and breadth of immune responses, while simplifying vaccine availability and delivery logistics. The U.K. COVID-19 Heterologous Prime-boost study released their initial report on adverse reactions observed with this vaccine regimen in The Lancet last week. Although adverse reactions were reported more frequently, they were mild and short-lived.

Key points:

  • Feverishness, chills, headaches, and muscle pain were reported more frequently when different vaccine products were combined.
  • Most adverse reactions were mild and were observed 48 hours after immunization.

COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. All vaccines currently used in Canada follow a two-dose schedule, with a “prime” shot followed by a “booster” shot some weeks later, with the same vaccine. It has been proposed that prime-booster immunization schemes using different vaccines may increase the intensity and breadth of immune responses. These ‘mix and match’ vaccine strategies could also have some practical benefits as vaccine delivery logistics would be greatly simplified.

Researchers at Oxford University in the U.K. launched a study in early February to evaluate the possible benefits of a ‘mix and match’ COVID-19 vaccine regimen. The U.K. COVID-19 Heterologous Prime-boost study is collecting data to determine the breath of the immune response generated after receiving two different vaccine products versus receiving the same vaccine twice. The researchers are evaluating the effects of combining the Oxford-AstraZeneca and Pfizer-BioNTech vaccines, with either as the first or second shot. A second study includes the vaccine products from Moderna and Novavax (not currently approved in Canada) as booster shots. A preliminary report on the expected adverse reactions and safety data was released last week and the initial immunological results are expected by June 2021.

The recorded adverse reactions with either the Oxford-AstraZeneca or Pfizer-BioNTech vaccines were self-reported as local (such as pain at the injection site) or systemic symptoms (such as fever or fatigue) within seven days after either the first and second doses. Participants received the vaccines at 28-day intervals. Most of the adverse reactions were mild, observed within 48 hours after immunization, and there were no hospitalizations following vaccination. However, those who received a different vaccine for their second dose did report more adverse events after the booster than people who had received a booster with the same vaccine as for their first dose. For example, 34% of the participants who received Oxford-AstraZeneca first and Pfizer-BioNTech second and 47% of the participants who received Pfizer-BioNTech first and Oxford-AstraZeneca second, reported feverishness. This was compared with 10% of participants who received Oxford-AstraZeneca twice and compared to 21% of participants who received Pfizer-BioNTech twice. Similar trends were observed for chills, fatigue, headache, joint pain, malaise, and muscle ache.

Shaw RH, Stuart A, Greenland M, Liu X, Nguyen Van-Tam JS, Snape MD and the Com-COV Study Group. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. The Lancet. 2021. doi: 10.1016/S0140-6736(21)01115-6.