Antibiotics hinder vaccine response in infants

Australian researchers have found that giving antibiotics to newborns can reduce their immune response to vaccines, likely due to changes in gut bacteria.

Published in Nature, the team’s study followed 191 healthy babies from birth to 15 months, tracking how their immune systems responded to vaccines. The project brought together collaborators from a dozen institutions around Australia, co-led by Professor David Lynn, a program director at the South Australian Health and Medical Research Institute (SAHMRI) and Professor of Systems Immunology at Flinders University, and Professor Helen Marshall, Medical Director of the Vaccinology and Immunology Research Trials Unit (VIRTU) at the Women’s and Children’s Hospital.

According to Lynn, infants who received antibiotics in the first few weeks of life had significantly lower levels of antibodies against multiple different vaccine antigens at seven and 15 months.

“We’ve known for some time that gut bacteria play an important role in shaping the immune system, but this study provides strong evidence that early-life antibiotics can disrupt that process in a way that weakens vaccine responses,” he said.

“This raises important questions about how we use antibiotics in newborns and what we can do to reduce any unintended consequences.”

The research team found that babies given antibiotics had fewer beneficial gut bacteria, particularly Bifidobacterium, at the time of vaccination. This reduction was linked to weaker immune responses when researchers measured antibody levels six and 14 months later.

“What’s really interesting is that babies who had fewer Bifidobacterium in their gut before vaccination had lower antibody levels months later,” Lynn said. “This suggests that these gut bacteria play a key role in helping the immune system respond optimally to vaccines.”

The study went on to investigate the effects of Bifidobacterium on vaccine responses in germ-free mice, mice with no microbiota that are kept in special sterile isolators, and demonstrated the critical role that these, but not other, bacteria had in supporting optimal immune responses to vaccination in these mice. SAHMRI has one of only three fully equipped germ-free mouse facilities in Australia that enables such work to be done.

The researchers found that babies whose mothers received antibiotics during labour did not have reduced vaccine responses. It’s believed this may be because direct antibiotic treatment in the first few weeks of life has a more persistent impact on gut bacteria than exposure during labour.

“This is an important distinction because it suggests that not all antibiotic exposure carries the same risks when it comes to the impact on the infant’s immune responses,” Marshall said.

The study highlights the need to consider the broader impact of antibiotic use in early life, beyond just concerns about antibiotic resistance, as well as the need to discern whether other factors play a role in shaping immune responses to vaccines. Future studies will look more closely at how antibiotics affect different types of vaccines, as some vaccines seem more dependent on gut bacteria than others.

"Antibiotics are essential, and we absolutely need to use them when necessary, but our research suggests we should be more mindful of their potential long-term effects on the immune system,” Lynn said.

“If we can find ways to mitigate those effects, such as through targeted probiotic use, we could improve vaccine responses and overall health in infants.”

The study has resulted in what is being described as a first-of-a-kind human trial, also being led by Lynn and Marshall, which will investigate if the infant immune response to vaccines can be improved by giving probiotics to babies treated with antibiotics in the first week of life.

As part of the trial, newborns will be randomised to receive either a daily probiotic or placebo for two weeks before they have their first immunisations. The probiotic is already used in preterm infants for protection against necrotising enterocolitis (NEC) and has been proven safe for consumption. Blood and stool samples will be collected to assess how the probiotics impact the infants’ microbiome and subsequent vaccine responsiveness.

“This will provide evidence as to whether this simple probiotic intervention can support optimal immune responses to vaccination in early life, and we’ll also be able to identify the molecular mechanisms governing the differences in vaccine efficacy,” Lynn said.

The trial could have broader implications for infants whose microbiome may be disrupted for other reasons, such as those born by C-section, or for those infants in low-income countries who incur repeated gastrointestinal tract infections and malnutrition which can similarly deleteriously impact the infant’s microbiome. Trial recruitment is set to start in the coming months.

“Our findings could also be relevant to long-term child health, given prior associations between antibiotic exposure and an increased propensity to develop conditions such as allergies, asthma and obesity,” Lynn said.

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