A study published in Nature communications biology in April 2023 identifies “several factors associated with COVID-19 vaccine-induced adaptive immune responses”. Among the findings explored in the paper, “gut microbial fucose/rhamnose degradation pathway” is “positively correlated” with mRNA expression of the activation protein 1 (AP-1), a gene encoding an enzyme that promotes AP-1 expression, and “inversely correlated with BNT162b2-induced T-cell responses”. The authors use a systems biology approach to gain insight into these factors.  

COVID-19 vaccines 

The paper states that vaccines containing mRNA encoding SARS-CoV-2 spike antigen, like Pfizer’s BNT 162b2, “can effectively protect people” against COVID-19. This protection relies on “innate immune sensing of BNT162b2 by cytosolic RNA sensors after vaccination, leading to activation of “spike-specific T-cell and antibody responses”.  

Although two doses induce “detectable” levels in most people, “adaptive immune responses vary widely among individuals”. This variation is associated with a range of factors, such as SARS-CoV-2 infection history, sex, and age, but causes remain “largely unknown”.  

Systems biology 

NIH describes systems biology as a biomedical research approach that seeks to understand the “larger picture” by “putting its pieces together”. The study suggests that recent studies focused on a systems biological understanding of responses to vaccination provide “important insight into factors associated with inter-individual variation”.  

“Through comprehensive analysis of immune states of blood cells at baseline and early vaccine responses, specific immune cell populations and transcripts have been identified as correlates of antibody or T-cell responses induced by vaccination against influenza virus, hepatitis B virus, and malaria.” 

Additionally, studies have demonstrated that gut microbes are “associated with vaccine-induced adaptive immunity”. Thus, these factors can be “predictors of vaccine responses” and could be “potential therapeutic targets to improve vaccine responses”. Despite this, the “variability of immune states and gut microbes” associated with the COVID-19 mRNA vaccine responses remains “unclear”. Therefore, the study demonstrates the link between BNT162b2-induced human adaptive immune responses and “specific immune and gut microbial parameters”. 

What does the study find? 

The authors identify “various human immune cell populations and transcripts” as well as “gut bacterial taxa and functional pathways” that are associated with BNT162b2-induced vaccine responses.  

“Notably, the baseline transcription module related to the AP-1 transcription factor network was positively associated with BNT162b2-induced antibody response and negatively associated with T-cell responses.” 

Furthermore, baseline expression of AP-1 genes was “inversely correlated” with T-cell responses, and the gut microbial fucose/rhamnose degradation pathway was “inversely correlated” with T-cell responses.  

“These findings advance our understanding of the contribution of immune and microbial factors to inter-individual variations in vaccine-induced adaptive immunity.”  

The results indicate a “functional link” between the gut microbial fucose/rhamnose degradation pathway and the host immune system. However, further studies are needed to explore the “clinical significance and molecular mechanisms of interactions” between the pathway and vaccine-induced T-cell responses.  

What other factors might be at play in determining a vaccine-induced immune response? To learn about how time of vaccination might play a role, click here.

The study can be accessed at this link