Despite the existence of vaccines against pneumococcal infections such as otitis media, sinusitis, and meningitis, the prevalence of pneumococcal pneumonia remains high. Currently, around 100 new serotypes of Streptococcus pneumoniae have been identified, and the increase in pneumococcal infections caused by serotypes not covered by the vaccine has become a concern. This situation underscores the need for a more versatile vaccine.

Building on their previous success in mucosal responses in 2019, in which they developed a mucosal vaccine that caninduce antigen-specific mucosal immune responses, mainly immunoglobulin A (IgA), on the target mucosal surface, a research team led by Professor Satoshi Uematsu and Associate Professor Kosuke Fujimoto from the Department of Immunology and Genomics at the Graduate School of Medicine, Osaka Metropolitan University, has this time set out to bridge the gap in pneumococcal pneumonia vaccination efficacy.

To successfully develop a novel pneumococcal vaccine, the research team combined its proprietary mucosal vaccine technology with pneumococcal surface proteins that can cover a wide range of serotypes. Experiments conducted on mice and macaques have demonstrated the vaccine’s efficacy in suppressing pneumococcal pneumonia in the target animal groups.

“This research has succeeded in developing a vaccine formulation that can potentially be used in humans, which will advance the development of this vaccine for clinical applications,” said Professor Fujimoto. “This next-generation vaccine technology is expected to contribute to the treatment of infectious diseases in the future.”

“If you’re in a resource-rich environment — meaning for a child that you’re safe, your meals are coming, someone is at home for you, you’re surrounded by adults that are protecting you — you’ll try new things,” says Seth Pollak, a University of Wisconsin-Madison professor of psychology who studies childhood adversity. “And that’s how you discover and learn about the world.”

But not every exploration will be rewarding and, according to a new study of childhood exploration and parental predictability that Pollak and collaborators today published in the Proceedings of the National Academy of Sciences, kids who don’t believe they have the support of reliable parents are less willing to risk the unknown.

“What’s unseen around that corner could be golden, but you could also end up in some bad situations,” Pollak says. “You could end up ordering a bad meal or touching something that hurts you. You could end up in a bad relationship or with an empty wallet. And so, we thought, in order to have the confidence to try something new, you have to feel like you’re supported and relatively safe — like you can afford to make a bad call.”

The researchers studied decisions that more than 150 children ages 10 to 13 made while playing games designed by C. Shawn Green, a UW-Madison psychology professor. The games offered the children opportunities to risk a little and explore for potential gains.

One game, fashioned after a pair of casino slot machines, gave players a history of payouts on just one of the machines — information that helped them understand their expected winnings if they kept pulling that machine’s handle. The other machine’s history was a mystery, and investing a pull there was more of a risk, but also potentially a bigger return.

The other game, in which the kids collected apples in virtual orchards, featured diminishing returns as players continued to pick from an individual tree. With limited time, would the players move to new trees, with unknown bounties? Or would they plug away at the tree they knew best?

The kids and their parents also participated in a battery of surveys and assessments. The researchers gauged the stress the children experience and the predictability of their lives — based on factors like parental job loss, divorce, death or illness in the family, and changing schools and homes — as well as children’s own views about whether or not their parents were reliable and predictable.

Yuyan Xu, a UW-Madison graduate student and first author of the study, asked children to respond to questions about how they’ve experienced their relationships, such as: When my parents say they’re going to pick me up, can I count on them to be there? When my parent makes a promise, do they follow through on it? Do I typically know how my parents are going to react to different kinds of situations?

The less reliable and predictable the kids felt their parents were, the less likely they were to take exploratory risks in the games they played. They were less likely to give the mysterious slot machine a chance or choose to move to a different apple tree.

“The children from more stable backgrounds, they play around and experiment in our games. They use that to get a sense of how things work, maybe earning them more money or more points,” Pollak says. “Kids from unstable backgrounds just don’t play that way. They stay within a narrower range of possibilities. They prefer to stick with what they already know, even if it’s limited, rather than taking a chance at a higher possible reward.”

The researchers found those self-imposed limits on risk were not related to the more objective measures of stress and unpredictability on the kids’ lives or even on parental reports that didn’t necessarily agree with their child’s perceptions of their relationships. There wasn’t a correlation between lack of risk-taking and levels of anxiety or neuroses, or of the kids’ feelings about the rest of the world outside their family. If they felt their parents were unreliable and unpredictable, they were less willing to explore.

“I think it makes sense,” Pollak says. “Their brains are doing exactly what we want our brains to do, right? If you really feel things are not predictable and you don’t know how things are going to land, you’d stick to what works and what’s familiar. You wouldn’t waste your resources on something that could all fall apart.”

The researchers ran their experiments first with a group of nearly 80 kids, then repeated it with a second group of just over 80 more to confirm their results.

“The interesting thing here is that there seems to be a way in which our early childhood experiences are calibrating how we decide to make these decisions years and years down the line and in these really different kinds of situations,” says Xu.

Openness to exploration wouldn’t be the only important aspect of childhood enhanced by stability. Language development, sleep quality, stress regulation and other subjects of childhood development research have been tied to predictability in children’s lives. Pollak plans to delve further into the relationship between predictability and exploration to see how rifts might be healed.

“What can we do for kids who view their history of interpersonal relationships as unstable?” he says. “We might not be able to change the relationships by the time we understand them to be unpredictable. But could we change the way kids think about them, how they act on them? If that is flexible, maybe we can tune those kids into the benefits and rewards of exploration to help foster kids’ learning.”

This research was supported by grants from the National Institutes of Health (R01MH61285 and P50HD105353).

The study was published in the journal Neuropsychopharmacology.

Previous research has shown that not only are high levels of stress and depression harmful to the person experiencing them, but they can also have long-lasting effects on their children if experienced during pregnancy. In recent years, studies have also revealed that discrimination and acculturation — or the changes that occur due to migration and the subsequent balancing of multiple, different cultures — can affect the adult brain. What’s less clear is how children might be affected by their parents’ experiences of discrimination and acculturation.

For the new study, the researchers assessed the degree of discrimination, acculturation, and distress experienced by 165 people while pregnant using established questionnaires. The participants were 14 to 19 years old, mostly Hispanic (88%), and lived in or near the Washington Heights neighborhood of New York City. The researchers then performed magnetic resonance imaging (MRI) to evaluate brain connectivity in 38 of the participants’ infants after birth.

The first step, researchers said, was to determine whether discrimination and acculturation are distinct from other types of stress or depression.

“We thought that some of these experiences might go hand-in-hand or overlap, in which case it would be difficult to measure the effects of discrimination or acculturation on their own,” said Dustin Scheinost, associate professor of radiology and biomedical imaging at Yale School of Medicine and senior author of the study.

Scheinost and his colleagues from Columbia and Children’s Hospital of Los Angeles used a data analysis program that assessed all of their separate questionnaire measures of acculturation, discrimination, stress, depression, childhood trauma, and socioeconomic status, and organized them into groups by how similar the data anlaysis program determined them to be. Doing this, researchers say, helped them understand the degree to which different measures might be used to evaluate similar experiences.

“That analysis clustered measures of stress and depression and separately pulled out discrimination and acculturation measures as their own distinct variables,” said Scheinost. “That told us that while these experiences of discrimination are related to stress and depression, they are separate enough that we can look at their unique effects.”

When the research team analyzed the MRI images of the infants’ brains, they found differences in the children whose parents reported experiencing discrimination while pregnant.

The amygdala is an area of the brain associated with emotional processing and it’s very vulnerable to prenatal stress, said the researchers. Prior research has found that early experiences of adversity can have measurable impacts on amygdala connectivity in infants, children, adolescents, and adults. A growing body of evidence also suggests the amygdala is involved in ethnic and racial processing, such as differentiating faces of people from different races or ethnicities, for example.

When the researchers assessed connectivity between the amygdala and another region of the brain called the prefrontal cortex, which is associated with higher-order functioning, they found that children of people who experienced more discrimination while pregnant had weaker connectivity between the two brain regions.

“Our finding was consistent with what you expect to see in the brain of those affected by early life adversity either pre- or postnatally,” said Scheinost.

The takeaway, said Scheinost, is that while discrimination and acculturation affect the brain in ways other types of stress do, there is something unique and important about these particular experiences that should be better understood. Future research, he said, should focus on whether other populations are affected in similar ways and what underlies the effects.

“We don’t fully know why this happens,” said Scheinost. “So we need to investigate the biological mechanisms that carry these experiences of adversity from parent to offspring.”