No, AstraZeneca can’t claim that T-cells trump antibodies in the fight against Covid-19

I was just a tad surprised when I heard Pascal Soriot, chief executive of AstraZeneca, suggesting on Tuesday that the problem of the escalating coronavirus cases in mainland Europe was down to the fact that they chose the wrong vaccine to protect their elderly.

Soriot's claim was simple. By focusing on mRNA vaccines and the antibody argument, EU countries had overlooked the greater and longer-lasting protection of T-cells; something he suggested that Oxford-AstraZeneca’s Chimpanzee Adenovirus (ChAd) vaccine was superior at delivering.

It reminded me of the early days of my own scientific career, when HIV vaccine researchers could be split into two clear camps: strong supporters for T-cell protection and those for whom antibodies were everything.

But does the science support such a bold assertion – are there fundamental differences between the immunity generated by mRNA and ChAd Covid-19 vaccines?

First, let’s dismiss one myth. That waning antibody levels mean that people have lost their antibody protection. We know that memory cells lurk within, ready to spring into action and produce copious quantities of antibody if ever they meet the virus again.

So what differences between the vaccines have been identified, especially when given to older people?

One relatively small study showed that shortly after administration of the second vaccine dose, antibody levels were greater in those receiving the Pfizer-BioNTech mRNA vaccine compared with the AZ vaccine. However, higher T-cell levels were detected in those receiving the AZ vaccine.

Both vaccines can generate T-cells and both generate antibodies. The question is, are the variations in the amount of each significant?

The first thing to consider is the type and level of immunity needed to prevent infection and, crucially, severe Covid-19. In the trade, we call these correlates of protection.

Both antibodies and T-cells are important
We know that antibodies are important in preventing initial infection of cells. However, T-cells are important, too. Some boost overall immunity, while others directly kill virus-infected cells.

We suspect that our best vaccines, like MMR, generate both types of immunity but the optimal balance of antibodies and T-cells is unknown. Assessing how able vaccines are at preventing severe disease is an effective way to measure the overall performance of the technology.

Analyses reported by the Office for National Statistics estimated that the Pfizer and AZ vaccines gave 96 per cent and 92 per cent protection against hospital admission, respectively, with Pfizer deemed better at preventing infection and mild symptomatic disease.

Clearly, a difference in T-cell number or potential durability does not impart the AZ vaccine with noticeable superiority within the UK, where both vaccines have been widely used.

And not all EU countries have relied exclusively on mRNA vaccines. The European Medicines Agency says around half of the EU member states have adopted a “mix and match” immunisation strategy, in which a different vaccine type can be used for the second dose.

Studies, including the Com-CoV trial, have shown that a second dose using an mRNA vaccine after an initial dose of AZ gives superior levels of T-cells than when using either vaccine alone.

The availability of different vaccine schedules – ChAd and mRNA used in various combinations – throughout many parts of Europe means it is difficult to make a strong link between rising cases and hospital admissions with exclusive use of one vaccine type.

So what might be at play – why are UK cases relatively stable and those in many parts of mainland Europe on a steep rise?

Certainly, vaccine uptake is relatively low, especially in many Eastern European countries. This allows the virus to spread. It also means that infections often result in serious disease and death. Overcoming vaccine hesitancy, especially in vulnerable groups, is a major challenge.

Vaccination rates in many EU countries, such as Germany for example, are comparable to those in the UK. Both have high levels in older vulnerable people, although hotspots of low vaccine uptake persist in some communities.

The most notable difference between the UK and Western European countries experiencing increasing levels of coronavirus infection was the baseline number of infections.