Breaking down the microbiology world one bite at a time
From the moment they are born, newborn babies are at high risk for bacterial infection, as their immune systems are still under development. Fortunately, mothers transfer protective antibodies to their babies both in the uterus and after birth via breast milk, providing an initial layer of protection against pathogen exposure. These transferred antibodies can effectively target pathogens that are exposed on the outside of cells (i.e. extracellular), but it is unknown whether they can fight pathogens hiding inside cells (i.e. intracellular). Hence, intracellular infections can pose significant health threats to newborns.
Recently, a study published in Nature revealed that transferred maternal antibodies can in fact protect against intracellular pathogens. Researchers in the lab of Dr. John Erickson (Cincinnati Children’s Hospital Medical Center) discovered that pregnancy triggers a specific modification to maternal antibodies that offers protection against a particular intracellular infection caused by Listeria monocytogenes (Figure 1). This pathogen can cause serious bacterial infection, leading to fever and flu-like symptoms. An estimated 1,600 people are infected with listeriosis every year, with pregnant women and newborns being the most susceptible. This study paves the way for developing infection-fighting treatments, as well as inspires advances in antibody-based therapies and vaccine development.
The research team conducted their studies using pregnant and newborn mice. They found that pregnant mice with Listeria-immunity gave birth to mice with high Listeria-antibody levels and hence greater protection against infection. These results confirmed that maternally-transferred antibodies can in fact protect against intracellular pathogens. Interestingly though, newborn mice with artificially transferred antibodies from Listeria-immune but not pregnant mice were still susceptible to infection. This revealed that pregnancy must trigger a specific antibody modification that “turns on” their immunity.
Intrigued by this result, the researchers next investigated how these antibodies gained their protective power. Turns out, a very small structural modification is responsible. This alteration occurs on a sugar molecule, known as sialic acid, found on the surface of the antibody. The research team found that during pregnancy, 6 atoms are removed from the sialic acid, in a process known as “deacylation” (Figure 2). Researchers hypothesized that this deacylation is catalyzed by an enzyme called “SIAE”, which is known to be produced more during pregnancy. Once deacylated, the antibody can then be recognized by specific receptors that activate Listeria immunity.
A new perspective on antibody-based therapies
Excitingly, lab-produced antibodies that contained the same sialic acid modification were found to protect newborn mice that were born without receiving the antibodies from their mother. Mimicking deacylation and other small structural changes on the sugars of antibodies presents a promising strategy for developing therapeutics to target not only Listeria, but a spread of other intracellular infections such as HIV and respiratory syncytial virus (RSV). This research highlights the importance of studying antibodies through the lens of pregnancy to unveil new molecular alterations for antibody-based therapies and vaccine development.
Link to the original post: Erickson, J. J.; Archer-Hartmann, S.; Yarawsky, A. E.; Miller, J. L. C.; Seveau, S.; Shao, T.-Y.; Severance, A. L.; Miller-Handley, H.; Wu, Y.; Pham, G.; Wasik, B. R.; Parrish, C. R.; Hu, Y.-C.; Lau, J. T. Y.; Azadi, P.; Herr, A. B.; Way, S. S. Pregnancy Enables Antibody Protection against Intracellular Infection. Nature 2022, 606, 769–775. https://doi.org/10.1038/s41586-022-04816-9.
Featured image: Made by author and BioRender