Should we really mix and match vaccines?

The latest data may have the answer to one of the biggest questions surrounding Covid-19 vaccine rollout.

Photo by Daniel Schludi on Unsplash

Never before has there been such a buzz around who got which type of vaccine. This hot new topic of conversation has been rising since the start of the Covid-19 vaccination programme, with some who had never before heard of Pfizer or AstraZeneca now acting like brand ambassadors. Although it may not be quite as arbitrary as car or phone brands, it certainly seems as though many more people are now aware of, and care about, where their medicine is coming from.

More recently, the conversation has shifted to whether mixing different vaccine brands, known as using a heterologous vaccine schedule, affects the efficacy and safety of the Covid-19 vaccines. Scientists have pointed out the potential benefits that combining vaccines would have in terms of manufacturing and accessibility reasons. “At any time, a pharmaceutical company can have a manufacturing issue, whether that’s a contamination problem or a shortage of a reagent, so it’s helpful to have options.” says Pedro Piedra, a professor of molecular virology at Baylor College of Medicine in Houston. However, WHO advisers had previously warned against using a combination of different vaccines until more is known about its effects.  The key metric to measure is the immunogenicity of the vaccine - the ability to stimulate an immune response against foreign antigens.

The National Institute of Health (NIH) in the US and the University of Oxford have recently published data from their studies on whether immunogenicity is affected by the mixing of vaccine candidates, so what’s the verdict? 

Recent data on mixing vaccines

The NIH set out to investigate whether the protective immunity built against Covid-19 differed between double-vaccinated people who had received a booster shot of the same brand versus a different brand. Interim data from the study demonstrates that those who had a booster shot of a different brand of vaccine had higher antibody levels against Covid-19 than those who had a booster shot of the same brand. Those who had a J&J-Moderna schedule (in that order) experienced a 76-fold increase in antibody levels, compared to the four-fold increase seen with the J&J-J&J schedule - an indisputably superior improvement in immunogenicity.

This is encouraging news that consolidates results found in August by the University of Oxford’s Com-COV study, which also looked into the efficacy of vaccine combinations with the Pfizer and AstraZeneca (AZ) vaccines. The study found that all four schedules induced concentrations of anti-spike antibodies to at least as high as an AZ-AZ schedule, but by far the biggest increase of antibodies came after an AZ-Pfizer combination. Interestingly, the second biggest increase came from those with a homologous schedule of Pfizer-Pfizer which beat out the combination Pfizer-AZ, suggesting that not all combinations of vaccines may be more effective.

However, the mix-and-match vaccine schedule is arguably superior for its effectiveness in stimulating both cellular and humoral responses against Covid-19, both of which are vital for a strong immune defence. AstraZeneca and J&J vaccines are composed of the old-school method of using attenuated adenovirus vectors (ChAd), whereas Pfizer and Moderna employ the newer method of mRNA vectors. mRNA vaccines were shown to be more effective in stimulating a high antibody response, which targets viruses by tagging them and neutralising their dangerous effects. On the other hand, ChAd vaccines are especially good at inducing a T-cell response, which is responsible for killing the infectious cells that aim to harm us. Therefore, a heterologous vaccine schedule harnesses the advantages of both of these mechanisms to give more well-rounded protection. 

What does this mean for us?

The common theme found in the data is that mRNA vaccines are the most effective booster shots, whether or not the person has had the same or different brand in the initial two doses. The data mentioned above suggests that a booster of ChAd vaccine stimulates less antibody levels in both people double-vaccinated with ChAd and mRNA vaccines, compared to a booster of the mRNA vaccine.  

Luckily for us in the UK, the vaccine booster programme was informed on the basis of these kinds of studies and is offering those eligible the option of either the Pfizer or Moderna vaccine. The programme has been in full throttle since 16 September, with over 10 million people now having received a booster. It seems as though other countries are in the same boat, as much of Europe, the US, and others use the mRNA vaccines as the primary candidates for booster shots.

The questions being asked now are how long the protection acquired from the first two doses will last, and whether people outside of vulnerable groups will also require a booster shot eventually. The government has already accepted the advice of the Joint Committee on Vaccinations and Immunisation (JCVI) this week on boosters for those in the 40-49 age group, who were not previously eligible. The ongoing decision will inevitably depend on the latest data concerning the longevity of the immune defence built by the vaccine. As for now, booster programs are primarily targeting those who are older, immunocompromised or within healthcare jobs, as they are much more prone to come into contact with or become seriously ill from Covid-19.

Despite the now constant dissensions, the fact remains that the research shows booster shots to be highly effective in strengthening immunity against Covid-19. Especially as winter rolls round the corner, boosters are going to be essential for protecting the most vulnerable among us to ensure a happier and healthier festive season for us all.