Scientists observe surprising link between mindset and vaccine outcomes

New research published in Brain, Behavior, & Immunity – Health suggests that how people think about the COVID-19 vaccine might shape their experience—both psychologically and biologically. Individuals with a more positive mindset about the vaccine reported fewer side effects, less anxiety on the day of vaccination, and greater happiness in the days that followed. One specific belief—that side effects signal the vaccine is working—was linked with stronger immune responses, as measured by neutralizing antibody levels, even months after vaccination.

“We were interested in this topic because there’s increasing evidence that how people think about health interventions—like vaccines—can influence how they experience them,” explained study author Darwin A. Guevarra, an assistant professor of psychology at Miami University.

“Given the global rollout of COVID-19 vaccines and the variability in people’s reactions, we wanted to know whether psychological factors, like mindsets, might help explain differences in both biological and emotional responses.”

“This study adds to growing evidence that our minds and bodies are deeply connected. Even small shifts in mindset—how we frame what we’re experiencing—can potentially make a big difference in how we respond to medical interventions. That’s both exciting and empowering.”

The researchers conducted a prospective study involving 534 healthy adults in the San Francisco Bay Area. These participants had not yet been infected with COVID-19 and had not received a vaccine at the start of the study. They were enrolled between March and April 2021, just as vaccination campaigns were expanding. Each participant received one of three vaccines—Johnson & Johnson, Moderna, or Pfizer—and was tracked over time to see how their beliefs about the vaccine related to their biological and emotional responses.

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Participants answered surveys about their beliefs and feelings on the day of their vaccination and in the days afterward. These surveys assessed general optimism, anxiety, and emotional well-being, as well as more specific beliefs, such as whether they thought the vaccine would protect them, whether they believed their body would respond well, and whether they saw side effects as a sign the vaccine was working.

Blood samples were collected at three time points: before vaccination, about one month after, and again at six months. These blood samples were analyzed to measure levels of neutralizing antibodies—proteins the body produces to fight the virus.

When researchers analyzed the data, they found that participants who had a more positive overall mindset about the vaccine reported fewer side effects and less anxiety on the day they were vaccinated. They also reported feeling less stressed and sad, and more joyful in the days that followed. These effects were strongest on the day of vaccination and gradually declined over the next five days.

Importantly, these results remained even after accounting for other factors like general optimism, suggesting that specific beliefs about the vaccine played a unique role.

In more targeted analyses, the researchers found that people who believed their body would respond well to the vaccine or who believed the vaccine would protect them also tended to experience fewer side effects and less anxiety. They also reported better emotional outcomes.

Interestingly, however, these specific beliefs did not predict a stronger antibody response. The only belief that did was the mindset that side effects are a sign the vaccine is working. People who held this belief had higher neutralizing antibody levels at both the one-month and six-month follow-ups, suggesting a possible link between this specific expectation and the body’s immune response.

“What you believe about a vaccine before getting it might shape your reaction to it,” Guevarra told PsyPost. “People with a more positive mindset about the vaccine––such as believing it would work or that their body would respond well––reported fewer side effects, less anxiety, and better mood after vaccination. In some cases, specific beliefs, such as viewing side effects as a sign that the vaccine is working, were even linked to stronger antibody responses.”

This pattern raises the possibility that interpreting side effects as a positive sign could alter how the body reacts at a biological level. While the exact mechanisms remain unclear, one explanation is that this mindset reduces stress responses, which have been shown in previous studies to influence immune functioning. Another possibility is that the belief encourages greater engagement with the experience—people may be more likely to rest, hydrate, or otherwise care for themselves if they see symptoms as meaningful rather than threatening.

But the study, like all research, has limitations to consider. While the study design was prospective—meaning beliefs were measured before outcomes—it was not an experimental study. This means that the researchers cannot say for sure that mindsets caused the observed effects. It’s possible that other unmeasured factors played a role.

“Also, our sample generally had very positive vaccine mindsets to begin with, which might limit the range of effects we could observe,” Guevarra noted. “We need more research in groups with more varied beliefs about vaccination.”

Despite these caveats, the findings align with a growing body of research showing that how people think about treatments can influence how effective those treatments feel—and even how the body responds. Studies of non-deceptive placebos, for example, have shown that people can experience real emotional and physical benefits even when they know they are not receiving an active drug.

In one such study published in Nature Communications, people who were told a saline nasal spray was a placebo still experienced less emotional distress when shown upsetting images, and brain scans confirmed changes in neural markers of distress.

“Many people might find these results surprising, but they actually align with what we already know from decades of research,” Guevarra explained. “The brain communicates with every major physiological system, including the immune system. Studies in placebo science and psychoneuroimmunology have shown that our beliefs and expectations can influence how our bodies respond to illness and treatment. What’s new here is applying that framework to vaccine response—an area that hasn’t been thoroughly studied before. More work is needed to replicate these findings and uncover the biological pathways involved.”

The implications are wide-ranging. If mindset interventions can reliably improve how people experience vaccination, they could be used to ease fear, reduce side effects, and even boost immunity.

“Our goal is to better understand how mindset interventions could be used alongside medical treatments to improve health outcomes,” Guevarra told PsyPost. “If we can identify simple, scalable ways to shift people’s beliefs—like short videos or messages delivered before treatment—we might be able to reduce side effects, improve emotional well-being, and even enhance physiological responses.”

The study, “Examining the association of vaccine-related mindsets and post-vaccination antibody response, side effects, and affective outcomes,” was authored by Darwin A. Guevarra, Ethan G. Dutcher, Alia J. Crum, Aric A. Prather, and Elissa S. Epel.