Booster vaccination strengthens existing defenses
Memory B cells play a key role in adapting to new coronavirus variants
The SARS-CoV-2 virus is constantly mutating. As a result, vaccines become less effective and require regular adaptation. This was the case in 2025 with the JN.1 variant. An interdisciplinary team from Hannover and Göttingen has now investigated how the immune system responds to adapted vaccines. The findings were published in Nature Communications.
The SARS-CoV-2 genome is subject to constant mutations. Some of these mutations reduce the effectiveness of RNA-based vaccines, which consequently require regular adaptation. Until now, however, it was unclear how the immune system reacts to new virus variants. Do mainly pre-existing memory B cells become reactivated, or are new naïve B cells also activated on a larger scale? This question is particularly relevant for individuals whose immune responses have already been shaped by previous vaccinations and infections.
An interdisciplinary team of medical and scientific researchers from TWINCORE, Centre for Experimental and Clinical Infection Research in Hannover, the Hannover Medical School (MHH) and the German Primate Centre in Göttingen has therefore investigated the antibody and B-cell responses in a cohort of pre-immunized individuals following vaccination with an mRNA vaccine adapted to the JN.1 variant.
“Following the booster vaccination, we observed increased antibody binding and improved neutralisation of JN.1 and subsequent virus variants,” says Dr. Metodi Stankov. He is a research fellow in Prof. Georg Behrens’s research group at the Department of Rheumatology and Immunology at the MHH and one of the two first authors of the study.
Initially, the researchers found only B cells that either recognized exclusively the earlier Wu01 variant or were cross-reactive against both Wu01 and JN.1. “In contrast, B cells specific only to JN.1 increased only slowly, reaching their peak 21 days after vaccination,” says Dr. Matthias Bruhn, a postdoctoral researcher at the Institute for Experimental Infection Research at TWINCORE and also a co-first author of the article.
Subsequent single-cell RNA sequencing of the antigen-specific memory B cells and functional analyses of the corresponding monoclonal antibodies revealed that so-called somatic hypermutation drives specialization towards improved binding to JN.1 and more effective neutralization.
Somatic hypermutation is a natural maturation process of the immune system. It involves targeted changes in the gene segments of antibodies responsible for antigen binding. Through the subsequent selection of antibodies with particularly strong binding affinity, the immune system can specifically refine its defense against already known pathogens.
The researchers conclude from these results that it is primarily pre-existing memory B cells that adapt to the new viral variant following a booster vaccination. The activation of naïve B cells, by contrast, does not appear to be the dominant mechanism.
“The JN.1-adapted booster vaccination is associated with the adaptation of an existing memory B-cell repertoire to JN.1, as well as with improved neutralization of circulating and antigenically closely related viral variants,” says Prof. Ulrich Kalinke, Director of the Institute for Experimental Infection Research at TWINCORE and scientist in the German Center for Infection Research (DZIF).
“This study is a first step towards better understanding how the adaptation of vaccines to new virus variant influences the immune response,” says Prof. Georg Behrens, deputy coordinator of the DZIF's HIV research area. “Using the methods available today, we can track much more precisely how adapted vaccines modulate the immune response.”
The work was supported by the RESIST Cluster of Excellence and the DZIF, among others.
Source: Press release of TWINCORE - Centre for Experimental and Clinical Infection Research
