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During the COVID-19 pandemic, vast amounts of time and resources were allocated to vaccine research including identifying factors that may increase or decrease the immunogenic potential of vaccines. Although vaccine research has grown in recent years in conjunction with the COVID-19 outbreak, scientists have been researching the link between vaccines and the gut microbiota for decades and there is now a well-established a link between the infant gut microbiota and vaccine efficacy [1]. With infants receiving a substantial number of vaccines and having a lower functioning immune system than adults, it is imperative that vaccines perform to their highest potential, hence why they are often the cohort for gut microbiome and vaccine studies. In infants, the gut microbiota promotes the humoral and cellular immune responses to vaccines using many different mechanisms; it is key in the development and maturation of B cells that produce immunoglobulin (IgA) and memory plasma cells [1]. The gut microbiota also promotes antigen-specific T-cell responses via type I interferon production by plasmacytoid dendritic cells [1].
Previous research has demonstrated that in vivo models (subjects who had their normal gut microbiome disrupted by antibiotic-treatment) had poorer humoral responses to vaccine treatment due to a reduction in Th1 and Th1 responses as well as lower production of IgM and IgG [1]. Interestingly, after the subjects subsequently received faecal microbiota transplants, this impairment was reversable and immunogenic function was restored [1]. More specifically, the abundance of certain bacteria has been linked to different immune responses to vaccines; in a cohort of Bangladeshi infants, positive tetanus, hepatitis B and oral polio vaccine effects were observed in those with a high abundance of Actinobacteria, but a poor response was seen in those with a high abundance of Enterobacteriaceae [1]. These children were studied 2 years later, and it was found that those with a high abundance of Bifidobacterium sp., a common gut commensal in infants, had positive vaccine effects and had detectable CD4+ T-cell responses as well as IgG and IgA [1].
As previously mentioned, the rise of the COVID-19 pandemic saw a rise in vaccine research, but recently, a review written by Rossouw et al. investigated the role of the gut microbiota in vaccine response – including, COVID-19 vaccines [2]. Studies have identified a link between the gut microbiota and COVID-19 vaccine efficacy, with Bifidobacterium, Bilophila, Roseburia and Alistipes all having a strong association with COVID-19 vaccine immunogenicity [2]. In addition, research has investigated the effect of antibiotics, which disrupt the gut microbiome, and COVID-19 vaccine efficacy, and it was reported that subjects exposed to antibiotics within a 6-month period exhibited reduced seroconversion rates post-vaccine – however it was important to note that seroconversion rates were restored after the second COVID-19 vaccine dose, suggesting that the pre-existing gut microbiome disruption, caused by the antibiotic treatment, may have hindered antibody development [2]. With different aspects of the gut microbiota having such an impact on vaccine immunogenicity, it is a key subject area to study further, to understand the immunogenic process to a deeper level. In addition, the gut microbiota now lends itself as a possible treatment target to enhance vaccine potential, for example, using prebiotics and probiotics to alter the gut microbiome is a probable avenue to explore.
Pandemic outbreaks, such as COVID-19, are a huge health burden, so successful vaccination is vital to keep illness and fatalities at bay. To maximise vaccine efficacy, scientists have been able to identify potential microbiological and physiological markers that can enhance vaccine potential. It is hoped that vaccination programmes can take on board the effect of the gut microbiome on vaccine efficacy and provide interventions for those whose immunogenicity potential is not what it could be. Ultimately, research of this kind will be able to better public health – which is a goal we all strive for.
Written by DWS Microbiologist, Kirsty McTear
References
1. Jordan A, Carding SR, Hall LJ. The early-life gut microbiome and vaccine efficacy. The Lancet. 2022 Oct;3(10):E787–94.
2. Rossouw C, Ryan FJ, Lynn DJ. The role of the gut microbiota in regulating responses to vaccination: current knowledge and future directions. FEBS Journal. 2024 Aug 5;292:1480–99.
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