Could the gut microbiome be targeted to optimize Sars-CoV-2 vaccine efficacy?
By Dr. Genelle Healey
BC Children’s Hospital Research Institute University of British Columbia Vancouver, Canada
About this article
The primary goal of a successful SARS-CoV-2 vaccine, which is the main hope in controlling the Covid-19 pandemic, is to confer robust and long-lasting immunity for as many people administered the vaccine as possible. Despite several vaccines being deployed worldwide to manage the SARS-CoV-2 pandemic ongoing Covid-19 outbreaks demonstrate that the pandemic is far from over. Development of novelstrategies to help control the spread of the virus and/or enhance the efficacy of SARS-CoV-2 vaccines may prove useful in the fight against Covid-19.
SARS-COV-2 VACCINE EFFICACY
Vaccines are administered to challenge both the innate and adaptive immune systems. One common biomarker of lasting immunity and protection against SARSCoV- 2 are antibody responses. For reasons still poorly understood antibody responses to SARS-CoV-2 vaccination are highly variable between different people . Based on results from clinical trials SARS-CoV-2 vaccine efficacy for approved vaccines ranges from around 60 to 92% against the original SARS-CoV-2 strains but vaccine- induced protection towards SARSCoV- 2 variants of concern (i.e., alpha, beta, delta, and gamma) appears to be lower . Heterogenicity in vaccine responses between people, reduced vaccine efficacy with variants of concern and potential waning of vaccine efficacy over time all compromise the continued efforts to control the spread of SARS-CoV-2. Therefore, gaining a better understanding of the factors driving variations in SARS-CoV-2 vaccine efficacy in the short and long term is fundamentally important.
FACTORS THAT AFFECT VACCINE IMMUNOGENICITY
Given that everyone receives the same standardised vaccine dose, but immune responses vary widely, it is highly likely that factors other than vaccine type effect vaccine efficacy. Mounting evidence suggests that factors such as age, chronic disease, poor health behaviours, depression, and stress impact the immune system’s ability to respond to vaccines (Figure 1) [3-5]. These findings have been demonstrated across several vaccine types, so it is likely translatable to SARS-CoV-2 vaccines. Interestingly, most of the factors outlined above have also been shown to impact the composition and functional capacity of the gut microbiome. It is, therefore, plausible that gut microbiome dysbiosis driven by host factors could be implicated in the differing vaccine responses observed.
Factors influencing vaccine effectiveness.
Adapted from .
TARGETING THE GUT MICROBIOME TO ENHANCE VACCINE EFFICACY?
The gut microbiota is a collection of bacteria, fungi, viruses, and archaea that reside in the gastrointestinal tract and have co-evolved with their host over time. These microbes perform many important functions, one of which is regulating local and systemic immune responses. Interestingly, certain gut microbiota profiles (i.e., higher abundance of Actinobacteria, Clostridium cluster XI and Proteobacteria) have been associated with greater vaccine immunogenicity against viral infections such as HIV, influenza, and rotavirus [6-8]. A recent study reported that antibiotic-specific disruption of the gut microbiome (i.e., dysbiosis) led to impaired post influenza vaccine-induced antibody neutralization as well as lower concentrations of vaccine-induced antibody responses . Another study using both antibiotic treatment and germ-free mice demonstrated that sensing of a bacterial motility component (flagellin) by a receptor found on immune cells (toll-like receptor 5 [TLR5]) was necessary in promoting a robust vaccine response . This and other similar studies  provide evidence of the important role the gut microbiota plays in vaccine efficacy (Figure 1). However, to date no studies have investigated what impact the gut microbiota has on SARS-CoV-2 vaccine efficacy. Thus, future research which determines whether specific gut microbiota signatures impact SARS-CoV-2 vaccine efficacy are paramount. Additionally, microbiome-targeted therapies, i.e., prebiotics and probiotics , could be utilized as a vaccine adjuvant (an agent used to accelerate, enhance and/or prolong antibody specific immune responses) to enhance SARS-CoV-2 vaccine immunogenicity. Specifically, intranasal administration of lactic-acid bacteria (e.g., Bifidobacterium and Lactobacillus) has been shown to enhance resistance to viral infections and improve influenza vaccine efficacy [12, 13], therefore, oral delivery of live bacteria (probiotics) could boost vaccine specific immune responses if given alongside SARS-CoV-2 vaccines.
Irrespective of global vaccine deployment and targeted public health measures the Covid-19 pandemic continues to persist. Vaccines are the main hope in controlling SARSCoV- 2; however, heterogeneity in vaccine responses compromises the fight against Covid-19. Several gut microbiome factors have been implicated in altering vaccine immunogenicity. Therefore, utilisation of the gut microbiome as a vaccine adjuvant has the potential to improve SARSCoV- 2 vaccine effectiveness.
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