Pfizer and Moderna boosters differ in antibody response

The booster vaccination against COVID-19 with mRNA vaccines strengthens the antibody defence against SARS-CoV-2. However, not every vaccine leads to exactly the same immune response. Researchers in Tübingen have now shown that the two most commonly used mRNA boosters – BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) – differ in the composition of the antibodies produced. Principal Investigator Peter Kresmer, Ruth Ley and Meral Esen (lead author) from CMFI were involved in the study. The Pfizer booster in particular more frequently leads to a so-called class switch in the antibody subgroups IgG2 and IgG4. The role these differences play in long-term protection is currently being intensively researched.

After vaccination or infection, the immune system produces antibodies that bind to the virus and neutralize it. These antibodies exist in different ‘versions’ – known as IgG subclasses. They have different tasks: While IgG1 and IgG3 have a strong pro-inflammatory effect and trigger a rapid immune response, IgG2 and especially IgG4 are considered to be more ‘regulatory’. IgG4 dampens excessive immune responses and typically occurs during repeated or prolonged stimulation of the immune system.

‘The fact that the composition of these antibody subclasses differs depending on the vaccine has been little studied to date. Our data show that after a Pfizer/BioNTech booster, the number of IgG2 and IgG4 antibodies increases more than after Moderna,’ explains first author Alex S. Siebner from the University Hospital of Tübingen.

Vaccines trigger different patterns

The study examined 165 healthy younger individuals (median 25 years) who had received a booster with either Pfizer/BioNTech or Moderna after two previous vaccinations. In a detailed antibody analysis, the researchers found that both vaccines significantly increased the total number of antibodies. However, the distribution within the subgroups was different.

In particular, those vaccinated with Pfizer/BioNTech showed significantly higher levels of the IgG2 and IgG4 subclasses against the virus's spike protein. In contrast, people who had previously been primed with a non-mRNA vaccine (AstraZeneca or Johnson & Johnson) did not show this effect.

Meaning for long-term protection

It is still unclear whether and how these differences influence long-term protection against severe disease progression. ‘IgG4 is associated with a more inhibitory immune response. This is not necessarily negative, but it could mean that the duration and quality of immune protection differ between vaccines,’ said Siebner.

The results show that the choice of vaccine could make a difference not only in the short term but also in the long term. ‘The immune response is more complex than can be measured by antibody levels alone. Our study provides another piece of the puzzle to better understand how the mRNA vaccines, which were rolled out on a large scale for the first time in the COVID-19 pandemic, work,’ Siebner summarises. 

(Source: Press release University Hospital Tübingen)

Original publication:
Siebner AS, Griesbaum J, Huus KE, Flügge J, Hopfensperger K, Michel T, Schneiderhan-Marra N, Sauter D, Kremsner PG, Ley RE, Dulovic A, Esen M. (2025) Class switch toward IgG2 and IgG4 is more pronounced in BNT162b2 compared to mRNA-1273 COVID-19 vaccinees. Int J Infect Dis. 159:107990. doi: 10.1016/j.ijid.2025.107990.