CEIRS Researchers Review the Effects of the Microbiome on Vaccination

NIAID CEIRS | Research Publication Commentary

de Jong SE, Olin A, Pulendran B. The Impact of the Microbiome on Immunity to Vaccination in Humans. Cell Host Microbe. 2020;28(2):169-179.

Researchers at Stanford University, part of the Emory-UGA Center of Excellence for Influenza Research and Surveillance, recently published a review focusing on how an individual’s microbiome can affect the physiologic responses to vaccination. Previous studies have found variance in vaccine response depending on geography, social status, route of vaccination, and chronic co-infections; recent work has looked at these factors while considering microbial effects as well. Here, the authors review studies assessing both human and mouse models, broad international representation, and the potential effects of age on vaccination efficacy and microbial populations. This is critically relevant work, especially in light of the race to develop and disseminate SARS-CoV-2 vaccines to the general public. The concept of herd immunity through vaccination is key element of the pandemic response, so understanding and predicting response to vaccination throughout society is critical.

Enterobacteria are a normal part of the microbiome.

The mammalian microbiota comprises bacteria, viruses, fungi, protozoa, and archaea that work symbiotically with the host to provide critical immunologic functions and are important to an individual’s personal ecosystem. The review focuses on the effects related to bacteria, as these components of the microbiome have the most research data available. It is postulated that the effects of the microbiota can be local to the digestive tract or disseminated throughout the body. Local effects in the gut may be through interactions between the products of metabolism and immune cells, and/or direct antigen presentation. These effects are especially relevant for oral vaccines, like polio or rotavirus vaccine which are often given to children. Whole-body effects are hypothesized to be related to circulation of pathogen-associated molecular proteins (PAMPs, often lipopolysaccharides from bacteria) or cytokines released based on immune detection of PAMPs. Alternatively, interaction between the immune system and bacterial antigens in immunologic hot spots like the spleen and lymph nodes can trigger antibody response into systemic circulation.

Several mouse models have assessed the role of microbiota in immune response and risk of systemic infection. While the results are not conclusive to specific bacteria or immune system function, it is becoming increasing clear that the microbiome does play a role in vaccine response. One study that demonstrated the simple presence of filamentous bacteria could prevent and/or cure rotavirus infection. Germ-free mice were used in a study relevant to vaccine response. The mice had reduced IgG and IgM production after vaccination with a non-adjuvanted influenza vaccine, and similar results were seen in mice without the ability to respond to bacterial proteins. It seems that the presence of protein in bacterial flagellin improves the antibody response to vaccination, potentially acting as a natural adjuvant.

Only a few strains of E. coli are pathogenic; most are a normal part of the microbiome.

Multiple human infant studies have assessed correlation between gut microbiota and vaccine response. In one paper, oral rotavirus vaccine efficacy was assessed in Ghanaian, Pakistani, and Dutch infants. Despite dissimilar environments, the microbiota of positive responders to the vaccine were more similar to other positive responders, even if they lived on another continent, than they were to non-responders in the same country. Another study in Bangladesh noted that infants with high levels of Bifidobacterium was correlated with a positive response to both oral and parenteral vaccines immediately and in the long-term. Antibiotic and vaccine response studies in adult humans yielded equivocal results but seem to suggest that dysbiosis (altered microbiome in response to antibiotics) decreases the response to seasonal influenza vaccine. Researchers hypothesize that this may be related to an inflammatory state secondary to bile acid decrease or bacterial metabolic products.

Finally, the authors discussed age and its implication on the microbiome. Understanding the microbiome’s role in vaccine efficacy may allow vaccines with fewer adjuvant components that are currently required for immune stimulation. This is relevant for very young individuals, as infants receive numerous vaccines during their early life. In older individuals, there is a diversity of microbiome types as well as co-morbidities like obesity and chronic infectious disease; these variables can confound research. Geriatric subjects have decreased bacterial production of short-chain fatty acids and other beneficial components in the gastrointestinal tract, generalized decreased function of immune system cells, and the breakdown of protective cellular junctions may increase an overall inflammatory state. The effect of the microbiome on this systemic “inflammaging” or “immunosenescence” is underexplored and is an emerging field in vaccine research.

Scientific research has increasing identified important roles for the microbiome in aspects of human health. This review demonstrates the breadth of mechanisms and effects associated with the microbiome on humans’ response to vaccination. Continued research in the field could reveal critical physiologic functions that will allow development of more effective vaccines, especially for young and elderly vulnerable populations. Most immediately, a greater understanding of our microbial populations may allow a safer and healthier emergence from the SARS-CoV-2 pandemic.