The relationship between gut microbiota, immunoglobulin A, and vaccine efficacy

(Press-News.org) Gut microbiota may be the key factor explaining why certain individuals do not respond well to the pneumococcal vaccine-a bacterium that can cause various diseases, such as pneumonia. This conclusion is drawn from a recent study led by the B Cell Biology Research Group at the Hospital del Mar Research Institute, published in Science Advances.

Researchers analyzed vaccine responses using genetically modified mouse models to study two types of pneumococcal vaccines-one commonly used in children and another in adults. Although these vaccines function through different mechanisms, both provide broad coverage. However, in individuals with a specific type of immunodeficiency, immunoglobulin A (IgA) deficiency, the immune system does not always mount an adequate response, leaving them vulnerable to respiratory infections that can lead to severe complications. The reason: poor regulation of gut microbiota.

Immunoglobulin A plays a crucial role in controlling gut microbiota. It regulates its function and ensures that its presence remains beneficial to the body. However, in the absence of IgA, the bacteria that make up the microbiota can overgrow and spread beyond the intestines. This overgrowth triggers an immune system response to keep the bacteria in check, but this response remains persistently active over time, leading to immune cell exhaustion.

According to Dr. Andrea Cerutti, a researcher at the Hospital del Mar Research Institute and ICREA, "The vaccine may be less effective in the absence of immunoglobulin A because bacterial molecules originating from the gut overstimulate the immune system, leaving it exhausted. This phenomenon leads to the production of an excessive amount of another antibody, immunoglobulin G (IgG).

Under normal conditions, "vaccines generate a response through pneumococcus-specific IgG antibodies. However, in patients with IgA deficiency, the lack of IgA reduces the vaccine's effectiveness”, explains Mauricio Guzmán, a Ramón y Cajal researcher at the Hospital del Mar Research Institute. This finding suggests that vaccination strategies should take this factor into account.

Early intervention

The study's authors highlight that while IgA deficiency primarily affects adults, its negative impact on the immune system can begin at a very early age. The study's results indicate that the abnormally increased IgG response to components of the gut microbiota and impaired response to vaccines begin very early in life.

For this reason, "we should explore the possibility of early supplementation with recombinant IgA antibodies, as a form of immunotherapy, to counteract the excessive immune response to gut bacteria and prevent immune system exhaustion," notes Dr. Cerutti. This approach could help prevent immune cells from failing to respond to vaccines after years of continuous immune activation caused by a lack of microbiota regulation provided by immunoglobulin A.

The research team believes these findings could lead to new preventing strategies for people at higher risk of developing severe pneumococcal infections, such as individuals over 65 and individuals with pathologies weakening the immune system, for whom vaccination is recommended. Additionally, the study's conclusions may extend to other vaccines as well. The researchers also point out that research is already underway to develop immunoglobulin A formulations capable of preventing microbial penetration across the intestine and correcting IgA deficiency.

The study included researchers from the Vall d'Hebron Research Institute (VHIR) and the Sant Pau Biomedical Research Institute (IIB-Sant Pau), as well as the Icahn School of Medicine at Mount Sinai and Weill Cornell Medicine, both in New York, United States.

Reference article

Gutzeit C, Grasset EK, Matthews DB, Maglione PJ, Britton GJ, Miller H, Magri G, Tomalin L, Stapylton M, Canales-Herrerias P, Sominskaia M, Guzman M, Pybus M, Tejedor Vaquero S, Radigan L, Tachó-Piñot R, Martín Nalda A, García Prat M, Martinez Gallo M, Dieli-Crimi R, Clemente JC, Mehandru S, Suarez-Farinas M, Faith JJ, Cunningham-Rundles C, Cerutti A. Gut IgA functionally interacts with systemic IgG to enhance antipneumococcal vaccine responses. Sci Adv. 2025 Feb 14;11(7):eado9455. doi: 10.1126/sciadv.ado9455. Epub 2025 Feb 12. PMID: 39937896; PMCID: PMC11817949.

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