Scientifically Speaking | Considering a mix and match approach to Covid vaccines
For most vaccine-preventable diseases, two or more shots are needed for both long-lasting and strong immune protection. For example, children require up to five doses spaced over months for diphtheria, tetanus, and pertussis (DTP). Even in adults, a tetanus booster is recommended every ten years.
All currently available vaccines for Covid-19, with the exception of the single-dose adenovirus vector vaccine from Johnson & Johnson, were approved clinically with two doses — a prime to build and train the immune response, and a boost to jolt it into producing even more antibodies and immune cells.
In clinical trials for approval of two-dose vaccines, adults were administered a prime and boost regimen with exactly the same vaccine type and dose. The only approved vaccine with a slightly different prime and boost is Sputnik V, which uses different cold-causing adenoviruses in two doses to deliver instructions for the body to make and mount an immune response.
A record-number of different types of vaccines have been approved for Covid-19 already; more are on the way. Some such as Covaxin are inactivated virus vaccines created with traditional approaches. Others such as adenoviruses vector vaccines, RNA vaccines, and protein subunit vaccines use molecular approaches.
Right now, those who have received one vaccine should adhere to health guidelines for their second doses. In the United States (US), for example, the only approved two-dose vaccines are mRNA vaccines made by Pfizer and Moderna. Those who have received one dose of Pfizer are not typically given a second Moderna dose and vice versa. But the US has not faced widespread shortages of either vaccine. Additionally, the US Food and Drug Administration has unfailingly stuck with the approved clinical trial data for vaccine doses and intervals. Still since the two mRNA vaccines are quite similar, considering administering one instead of the other for a second dose if there is a dwindling supply, is not a stretch.
In other parts of the world, mixing different vaccine types for the first and second dose (known as heterologous prime-boost) has been initiated. In particular, the AstraZeneca (Covishield) vaccine, which is a viral vector vaccine, is has been associated with a rare blood clot risk in younger populations according to some studies. In addition, there is a higher risk of a rare bleeding disorder. In many European countries, high-risk individuals who received the prime of the AstraZeneca vaccine have been advised to get a boost of Pfizer’s mRNA vaccine weeks later.
Currently, most of the data that is available is with respect to mixing the AstraZeneca vaccine and Pfizer/ vaccine. A study in the Lancet published on May 29 found that those who received either vaccine first and a second dose of the other, had higher rates of common side effects such as fever and pain compared to those who received the same vaccine. Reassuringly, there were no major safety concerns.
Research from Spain presented on May 18 that has yet to be published found that those who received the Pfizer boost after a first dose of the AstraZeneca vaccine had higher levels of antibodies than those who received only the AstraZeneca prime.
More recently, Barros-Martins and researchers showed in a preprint posted on June 3 that receiving a boost of the Pfizer vaccine after a prime of the AstraZeneca vaccine raises higher levels of neutralising antibodies against tested variants of concern than receiving two doses of AstraZeneca. In addition, those who had two doses of different vaccines had boosted immune cells responses.
None of these three studies demonstrates real-world effectiveness or how long protective immunity lasts, but taken together, they show that getting a boost of Pfizer after being primed by a dose of AstraZeneca is safe and results in a robustimmune response. In this case, heterologous prime-boost is the right approach.
Countries should test different heterologous prime-boost vaccine combinations to maximise the protection of their populations.
First, if one vaccine becomes scarce, those who are partially vaccinated may need to be offered a different boost vaccine for full protection. Second, the safety and adverse effects of mix-and-match vaccines needs to be determined before rolling out broadly. Third, the immune responses and effectiveness of mixing vaccines together needs to be gauged.
For other diseases, an unexpected finding is that heterologous prime-boost often results in stronger immune responses and more effective vaccines. This strategy has been beneficial for rabies and for Ebola. And so far, it seems to be the case for some Covid-19 vaccine combinations.
To my knowledge, there are currently no published studies on heterologous prime-boost with Covishield and Covaxin, but this research is vitally necessary since these are the two most widely available vaccines in India. Safety or supply issues with either could slow down India’s vaccination drive. We urgently need systematic studies that look at safety, immune responses, and real-world effectiveness of a mix-and-match approach with vaccines.
Anirban Mahapatra, a microbiologist by training, is the author of COVID-19: Separating Fact From Fiction
The views expressed are personal