Early Life Antibiotics Put Vaccine Response at Risk

The first years of life are an important time for microbiome development. Antibiotics, which can wipe out the gut microbiome, have long-lasting effects on metabolism, weight, and the immune system.¹ Doctors give antibiotics during the first week of life if there are signs of infection or if the newborn is at high risk for sepsis. Various studies have shown that between one and 14 percent of late-preterm and full-term babies receive antibiotics during the neonatal period meaning that microbiome development becomes disrupted in a large number of infants.²

Now, research published in Nature found that just 48 hours of antibiotics in the first week of life can dampen an infant’s vaccine response up to 15 months later.³

The research, led by David Lynn, an immunologist at South Australian Health and Medical Research Institute and Flinders University, and Helen Marshall, a vaccinologist at the Women’s and Children’s Health Network, tracked how the immune systems of 191 healthy, full-term, vaginally delivered infants responded to vaccines. They measured antibody titers after several routine vaccines, including vaccines that protein against pneumococcal infection, meningococcal infection, rotavirus, diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b.

For several vaccine antigens, the researchers observed that antibody responses at seven and 15 months were significantly lower in infants who received antibiotics shortly after birth. However, they did not see this effect in infants exposed to maternal antibiotics before or after delivery.

To dig into these differences, the researchers examined how antibiotics affected the microbiome in the first and sixth weeks of life. “Week six is a really important time point because that's when most of the infants get their first dose of vaccines, with the exception of the hepatitis B vaccine that is given at birth,” said Lynn. They found that while infants exposed to maternal antibiotics before delivery initially showed microbiome differences, including reduced levels of several Bifidobacteria species, most of these changes had resolved by the time of the first vaccine doses in week six. This could explain why they don’t see a difference in vaccine response after intrapartum antibiotics.

However, infants who were directly treated with antibiotics had a reduction in Bifidobacteria in their gut microbiome during immunization. Bifidobacteria are ubiquitous in the gut microbiota and are often included in probiotics, including those used in neonatal intensive care units to help reduce the risk of necrotizing enterocolitis linked to gut dysbiosis.⁴ Reduced Bifidobacteria correlated with a reduction in antibody titers against a range of vaccines. However, as Lynn noted, “In a clinical study, it’s difficult to tease apart correlation and causation.” So, the team turned to animal models to try and investigate whether the bacterium influenced the immune response to vaccines.

To do this, the team used germ-free mice, which lack a microbiome and exhibited impaired antibody responses to the pneumococcal conjugate vaccine. When they supplemented the mice with a mixture of Bifidobacterium species it restored immune responses to the vaccine. The team observed the same results when they supplemented the germ-free mice with commercially available probiotics one week before vaccination. “[These probiotics are] already used clinically in Australia in other contexts, and therefore would have strong potential for clinical translation,” said Lynn.

Vanessa Harris, an infectious disease researcher at Amsterdam University Medical Center who was not involved with the study, said that there are still a lot of unknowns about the interaction between the microbiome and vaccination responses. “Their work on Bifidobacteria is fascinating. I think they really contributed to the literature,” she added.

Harris noted that lower antibody titers don’t always translate to reduced protection, making it difficult to determine the clinical relevance. For example, most infants showed protection one month after the first vaccine doses.

Lynn and his team recently received funding to conduct a randomized control trial of probiotic intervention in infants who were exposed to antibiotics in the first week of life. They plan to give infants a probiotic or a placebo daily for two weeks before their first round of vaccines. Stool and blood samples will shed light on the infants’ microbiome and vaccine responses.

Lynn thinks probiotics could have a tremendous impact since the microbiome is easy to target. He explained, “Relatively cheap, scalable interventions like probiotics could play a beneficial role at relatively little cost in boosting protection that's mediated by vaccines.”

“If there could be a clinical benefit, it would be a fantastic intervention,” Harris added.