Microbial adjuvant

Gut Bacteria Boost Flu vaccine

Kirill Stasevich, Science and Life (nkj.ru )

Gastrointestinal microbes communicate very closely with the immune system, helping it to work: for example, we wrote that the microflora helps to adjust the immune system so that there are no allergies and autoimmune diseases, that intestinal bacteria help the immune system to create antibodies, that they help the immune system to fight tumors. And that's not all: recently an article appeared in the journal Cell, which states that the effectiveness of the influenza vaccine also partly depends on the gastrointestinal microflora (Hagan et al., Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans).

In fact, the first suspicions that microflora plays a role in vaccination appeared relatively long ago: back in 2011, Stanford researchers noticed that the effectiveness of the flu vaccine depends on the activity of one immune gene that encodes a receptor that recognizes the bacterial protein flagellin. A vaccine is either a killed (or weakened) pathogen, or its molecules: the immune system gets acquainted with how the pathogen looks, and subsequently, when an infection appears in the body, it will be able to get rid of it quickly. The fact that the acquaintance took place can be judged by the level of specific antibodies that immune cells must construct against pathogen molecules from the vaccine. If there are few such antibodies, it means that the vaccine was ineffective. So, experiments on mice have shown that if they turn off that receptor against bacterial protein, then the flu vaccination will go badly – there will be few antibodies against the virus.

But who should this receptor react to? The researchers suggested that on intestinal bacteria. Then, if we eliminate the bacteria, the effect will be the same – the immune system will react poorly to the vaccine. And so it turned out: when the mice were destroyed with antibiotics by their microflora, there were much fewer antiviral antibodies after vaccination.

In a new article in Cell, we are already talking about people. Eleven volunteers were given broad–spectrum antibiotics for five days - to kill their intestinal bacteria. On the fourth day, they were given the flu vaccine (for comparison, it was administered to eleven more participants who were not given antibiotics). The reaction to the vaccine was the same for those who received antibiotics and those who did not.

However, the level of antibodies against influenza was initially high in both of them. Most likely, this was due to the fact that they either had the flu recently or were regularly vaccinated against it. Then the researchers invited new volunteers who had not been ill with the flu for the last three years, nor had they received a vaccine against it. And now the effect of the loss of microflora appeared: those who were given antibiotics had a noticeably weaker reaction to the vaccine. Moreover, those whose microflora was destroyed with antibiotics had immunity that did not respond well to the vaccine for another three months.

That is, the microflora is important for the immune system when the virus is relatively new to it. Perhaps the same is the case with other viruses, not just the flu virus, and perhaps the same bacterial protein flagellin, which was necessary for mouse immunity, is important here. However, exactly how intestinal bacteria stimulate the antiviral response remains to be understood. On the other hand, if the results are confirmed in the following clinical trials with a large number of participants, then a warning about antibiotics and the effectiveness of the vaccine may appear in the recommendations for annual influenza vaccination.

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