New research reveals that influenza vaccine follows a consistent direction, but an uneven path, as it affects the immune systems of pregnant women and their developing babies 
by Tom O’Neill

Sing Sing Way, MD, PhD, and Elizabeth Schlaudecker, MD, MP.

Sing Sing Way, MD, PhD, and Elizabeth Schlaudecker, MD, MPH, have studied the maternal immune system for years, but along parallel paths. Now they are collaborating.

The medical community widely agrees that pregnant women should receive flu vaccinations, no matter how far along the pregnancy may be. The shots can prevent dangerous complications for women during pregnancy, reduce the risk of preterm birth, and even protect newborns from illness for months after birth. 

Now, after learning more about the complex ways that pregnant women and fetuses react and counter-react to each other, two researchers at Cincinnati Children’s are beginning to believe that the earlier that vaccines can be provided, the better.

Emerging research led by Elizabeth Schlaudecker, MD, MPH, and Sing Sing Way, MD, PhD, both of the Division of Infectious Diseases, takes a deeper look at how the immune systems of pregnant women and fetuses reacted to the H1N1 flu vaccine.

These investigations found that serological responsiveness to influenza vaccination in the mother declined with the progression of pregnancy. The declines were consistent, but did not follow a neat, incremental pattern. They did not track with simple trimester delineations, the usual method of distinguishing pregnancy-related changes.

A Matter of Timing

“It’s not the flu itself,” Way says, “It’s the immunological progressions that happen in the mother.” 

Way has studied for years how pregnancy changes the mother’s own immune system, so that her body will not attack the fetus as if it were a foreign invader.

This work has helped explain why pregnant women are more likely than non-pregnant women to suffer dangerous complications from flu infections.

Schlaudecker’s work explores how these concepts play out when using the H1N1 flu vaccine. Early results confirm that pregnancy-induced immunological changes in the mother are not defined by trimesters: vaccine responses are likely to be more similar between weeks 12 and 13 than between weeks 13 and 27, even though weeks 12 and 13 are in different trimesters. In fact, titers of antigen-specific IgG1 decreased by approximately 7 percent each week as pregnancy progressed to term.

“Conceptually, that makes sense,” says Way. “But no one until now has gone to the lengths Liz has in this paper to show that.” 

Based on these findings, Schlaudecker and Way agree: Women should be inoculated against the flu as soon as they learn they are pregnant.

The Key to Healthy Babies: Healthy Moms

As science reveals more about the complex ways pregnant women and fetuses inter-react, the field of reproductive immunology is enjoying a renaissance.

“There’s a lot of interest now,” Schlaudecker says, “because we’re finding that in several diseases that strike in the first few months of life, like respiratory syncytial virus, pertussis, group B strep, and influenza, infants are protected only if you can get the antibodies from mom.”

Among the complexities: pregnancy itself makes women more susceptible to severe complications from the flu. 

Schlaudecker observed this during field research in Honduras, and in re-examining medical records from the 1918 flu pandemic. However, newborn immune systems just aren’t up for fighting off influenza. One of their best immunological allies is gained from breastfeeding.

“Infants clearly receive serum antibody from mom for the first four months,” Schlaudecker points out. “However, if mom is breastfeeding, that protection lasts as long as breastfeeding continues.”

Two Researchers, Two Approaches, One Goal

This project is the first co-authorship for Schlaudecker and Way.

“She’s the technical and intellectual driving force of this project,” Way says. “My role is to serve as her mentor, her cheerleader. So she’s in a sense the first and senior author, although I will be listed last.”

The ongoing research also involves Cincinnati Children’s researchers from the divisions of Hospital Medicine, Biostatistics and Epidemiology, and Immunology.

“Our research is complimentary but not necessarily overlapping,” Way says. “We ask the same questions but use totally different model systems to answer them.”

Schlaudecker has focused more on clinical work in the past, using studies involving pregnant women. Way has focused on mouse models to study activity at the molecular level. The former is good at showing what is going on between the mother and fetus. The latter helps explore why.

“That’s why Sing Sing’s work is so interesting,” she says. “For some things like flu vaccines in pregnancy, we now know that immunological responses diminish, but other immunological components, like regulatory T cells, are enhanced. The path is not as linear and clear-cut as we used to believe it to be.” 

Now with this project, the molecular level and family level approaches appear to have found common ground: the health of moms and babies.