This randomized, double-blind, placebo-controlled study of the influenza vaccine will shed important light on how the immune system responds to different positive and negative social experiences. Building on the nuanced animal literature showing that, while animals exposed to an inflammatory challenge show reductions in social exploration consistent with the sickness behavior of social withdrawal, they actually show increases in social engagement behavior during interactions with a cage mate or pair-bonded animal. The present study will examine if a mild inflammatory challenge (receipt of the influenza vaccine) leads to change in actual social behavior in interactions, specifically toward a stranger and separately, toward a close friend. This study will also build on foundational animal research showing that an inflammatory challenge leads to social defeat behaviors in animals.

Psychologists have long appreciated that the mind can impact the body, and that bodily changes can influence the mind. Social psychologists in particular have conducted pioneering work on connections between the mind and body, showing both that social experiences elicit changes in numerous physiological systems and that physiological changes influence social cognition and behavior. Until recently, however, little attention has been paid to the connections between social experiences and the immune system. This is a critical gap knowledge, as seminal animal work shows that there are profound relationships between social experiences and immune system functioning that have yet to be fully explored in humans. Further, there are strong theoretical reasons to suspect that the immune system matters for social psychological processes even beyond times of sickness, though many of these connections are yet to be uncovered empirically in humans. Thus, to develop a comprehensive understanding of the mind-body connections that drive social behavior, researchers must integrate the immune system.

To address this critical gap in knowledge, the present study will examine the body-to-mind connection between the immune system and positive (i.e., interacting with a close other) and negative (i.e., social defeat) social experiences.

Why does the immune system matter for social behavior? There are good theoretical reasons why the immune system would be tightly interconnected to even normative, everyday social experiences beyond times of sickness. First, despite the common belief that the immune system only comes "online" in response to pathogens or physical injury, the immune system is in fact always active and fluctuates considerably even in the absence of an acute infection. Indeed, the immune system is responsive to both real and imagined situations that may signal increased probability of injury or infection. This includes everyday social experiences and situations of greater interest to social psychologists, from falling in love to being socially ostracized. Second, the brain is constantly monitoring the physiological state of the body and integrating this interoceptive information with signals from the broader environment to anticipate current and future metabolic demands and guide adaptive behavior. Thus, even relatively minor fluctuations in immune system activation beyond times of sickness can feed back to the brain to guide social cognition and behavior. In sum, there are strong theoretical reasons why everyday, normative social experiences may affect and be affected by immune system activation.

To date, social withdrawal is considered a hallmark "sickness behavior", based on both animal and human work showing that experimentally-induced increases in inflammation lead to less social exploration and greater feelings of social disconnection. However, other animal work suggests that the effects of inflammation on social behavior may be more nuanced than uniform social withdrawal, as some research shows that animals spend more time huddling with familiar cagemates, and form pair bonds more quickly when exposed to an inflammatory challenge. Further, recent work in the field of psychoneuroimmunology with humans replicates this, showing that an inflammatory challenge causes heightened (not diminished) neural responses to reminders of social connection. Yet to date, no known human work has examined if an inflammatory challenge causes changes in actual social behavior in humans, a critical next step in this line of research. Techniques from experimental social psychology are ideally-suited to address this next step, as social psychology has been at the cutting-edge of developing tools for eliciting and quantifying social behavior, particularly in the context of dyadic interactions that are likely to be important during an inflammatory challenge. This study will bring this important perspective to bear to further understanding of how immune system activation may cause changes in social behavior.

There is a storied history in psychoneuroimmunology (PNI) of using vaccines (e.g., influenza, typhoid) as a way to study immune system functioning. In vaccine trials, researchers typically examine how individual-differences in psychological processes (e.g., depressive symptoms, social connection) influence the effectiveness of the vaccine by examining the number of antibody titers produced following vaccination as a function of the individual-difference of interest. More recently, researchers have begun to use the influenza vaccine as a way to manipulate levels of inflammation, as the vaccine produces a small, but significant, increase in inflammatory markers (e.g., interleukin-6) in the 24-hours following vaccination administration. Prior work has examined the impact of vaccine-induced increases in inflammation on psychological processes such as mood and reward processing and shown that within-subject changes in inflammation in response to the influenza vaccine predict increases in daily negative affect and increases in reward responsivity. The present project will build on this prior work by adding a placebo-controlled (saline) condition, thus allowing researchers to determine if vaccine-induced changes in inflammation cause changes in social behavior. Using the influenza vaccine as an inflammatory challenge has numerous advantages over prior approaches: 1) It provides a public health service to the local community (i.e., given that vaccinations can prevent viral outbreaks) rather than making participants temporarily ill, as in the rhinovirus studies and endotoxin studies discussed previously; 2) The change in inflammation elicited by the vaccine is relatively small, thus mirroring more normative, day-to-day fluctuations in inflammation beyond times of sickness; and 3) Experimental procedures are less resource and cost-intensive, as almost every local pharmacy provides influenza vaccinations, and the cost is often covered by insurance and is relatively low (or free) for the uninsured. Given these advantages, the present study will use the influenza vaccine to examine if an experimental manipulation of inflammation causes changes in social behavior of interest to both social psychologists and psychoneuroimmunologists. In doing so, the study will advance a method that can be widely adopted by researchers to study how immune system activation feeds back to the brain to influence social experience.

Inclusion Criteria:

• 18-35 years old
• Have a same-gender friend willing to participate in the second study session

Exclusion Criteria:

• Are not a student
• Have already received the annual influenza vaccine or had the flu this season
• Report current illness/sickness symptoms, including upper respiratory symptoms
• Report any major medical conditions (e.g., diabetes, asthma)
• Use mood or immune altering medications (e.g., anti-depressants)
• Current regular nicotine/tobacco use (i.e., daily use of cigarettes or e-cigarettes)
• Have an allergy to eggs
• Have had COVID-19 in past two weeks
• Current or history of depression or anxiety
• Have had Guillain-Barre Syndrome
• Are allergic to vaccine or ingredients present in vaccine
• Have had an adverse reaction to a blood draw, including to needles or sight or blood
• Weigh less than 110 pounds
• Are unwilling to be video/audio recorded during the social interaction tasks
• Are unwilling to be unmasked during the social interaction tasks

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Beginning immediately following publication and ending 5 years after article publication.

Researchers who provide a methodologically sound proposal.

Two Sham vaccine participants were excluded from analyses due to use of hydroxyzine before session.

From the time of signing informed consent through ~30 hours later, after completion of study procedures