An article in Nature Communications in June 2023 presents research into age-associated B cells (ABCs) and how they can affect responses to COVID-19 vaccination. From the COVID-19 pandemic experience of extensive vaccination campaigns, it became evident that vaccination protects some patients better than others. Studies identify that these vaccines are less effective in patients with weakened immune systems, but not uniformly.  

The ABCs of immunity 

A statement from the University of Cambridge recognises that antibodies are produced by B cells, of which a “specific subset” is known as age-associated B cells (ABCs). Although the average proportion of ABC cells among B cells is less than 1 in 20 for a healthy individual, this increases as we age. Reasons for this increase are believed to include previous infections. 

The paper states that “although ABCs are associated with disease in autoimmunity, their role in vaccine immunity is uncertain”. Previous research gives rise to two questions for the authors:  

  • Are the ABCs found in patients treated with ICB (immune checkpoint blockade) equivalent to those found in other settings? 
  • Do these cells, when expanded through distinct mechanisms, have a positive or negative effect on humoral vaccine responses?  
Exploring the ABCs  

A team at the Medical Research Council (MRC) Toxicology Unit at the University of Cambridge examined ABCs from two patient groups. The first comprised people with an inherited condition that impairs immune system activity and the second comprised cancer patients on immunotherapy. The team also considered healthy individuals. The researchers were led by Dr James Thaventhiran.  

Emily Horner of Dr Thaventhiran’s lab stated that the aim was to learn how to “stratify vulnerable patients”. She explained that this means being able to work out “whether some patients were at greater risk from infection, even after vaccination, than others”. Thus, the work could lead to a clinical test to predict vaccine efficacy for both immunodeficient patients and the wider population, says Dr Thaventhiran.  

Using single cell RNA sequencing the researchers investigated cell activity in detail. They worked with Dr Nicholas Matheson from Cambridge’s Institute of Therapeutic Immunology and Infectious Disease to explore how the this could shape the course of a vaccinated individual’s immune response to live SARS-CoV-2.  

Surprising results 

The analysis of 4 patient groups suggests “a homogeneity of the ABC differentiation states irrespective of the specific cause”. Thus, the “pathological consequence of expanded ABCs is likely related to their increased frequency rather than an inherent difference”.  

“These results place ABC frequency as a predictive biomarker for reduced vaccine protection which could guide booster vaccination schedules for patients at risk of breakthrough infection.”  

Dr Juan Carlos Yam-Puc commented that the results were a “surprise”.  

“The age-associated B cells in these very different groups looked the same. The key difference was in the amount of these cells – the greater the proportion of ABCs in an individual’s blood, the less effective that individual was post-vaccination at neutralising the virus.”  

Dr Pehuén Pereyra Gerber says that this research could enable vaccine strength or priority differentiation between patients. Although the research considered COVID-19 vaccines it could also apply more widely, for example to the annual influenza vaccine.  

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