(PNA file photo by Joan Bondoc)
JERUSALEM – Tel Aviv University researchers have discovered a significant link between behavioral stress and the effectiveness of vaccines. Acute stress, they found, can both enhance and impair the body’s immune response to vaccination.
Led by Ph.D. students Noam Ben-Shalom and Elad Sandbank, under the guidance of Dr. Natalia Freund and Prof. Shamgar Ben-Eliyahu, the researchers conducted experiments on mice vaccinated with two different vaccines.
Their results suggest that stress can enhance both the quantity and potency of antibodies following vaccination. The findings were published in the peer-reviewed Brain, Behavior, and Immunity.
Acute stress is a mental state caused by an immediate threat — either real or imagined — involving the secretion of adrenaline and stimulation. This physical reaction is often described as the body’s “fight or flight” mode.
“During stress, the immune system produces large quantities of antibodies and stronger antibodies, to address the immediate infection, and this large energetic investment in the here and now comes at the expense of future immunological memory,” the researchers said.
In this study, Dr. Freund and her colleagues vaccinated mice with two different vaccines. One group was given the model protein Ovalbumin, the other a fragment of the SARS-CoV-2 spike protein also used in the Covid-19 vaccine.
Nine days later, just as the adaptive immunity became active and the production of antibodies began, the mice were subjected to a widely used behavioral paradigm simulating acute stress. Two and a half weeks after exposure to stress, namely 30 days after vaccination, the level of antibodies in the blood of vaccinated animals that had experienced stress was 70 percent higher compared to the control group.
This phenomenon was observed in animals vaccinated with either type of vaccine.
The researchers also found that the immune systems of the animals that had experienced stress was not cross-reactive to variants of the protein used in the vaccine. This indicated that following stress, the immune system was focused entirely on the original vaccine, showing no response to proteins that were only slightly different – such as variants of concern (VOC) of SARS-CoV-2.
In the second part of the study, Freund’s team tested whether humans also displayed post-stress immune impairment.
“For this purpose, we cultured B cells obtained from blood of people who had contracted Covid-19 in the first wave,” Freund said. “We then induced stress in these cultures using an adrenaline-like substance that stimulates the beta2 adrenergic receptor, which was identified by us in the first part of the study as a mediator of the response to stress in cells that produce antibodies in mice.”
The result?
“We discovered that just like in mice, human cells also exhibit a zero-sum game between the intensity and breadth of the immune response,” Freund explained. “When the adrenaline receptor is activated during stress, the entire immune system is stimulated, generating antibodies that are 100-fold stronger than antibodies produced in cells that had not undergone stress.”
She added that this also resulted in a narrower production of antibodies.
“The diversity of antibodies was reduced by 20-100 percent, depending on the individual from whom the cells were taken,” Freund explained.
“From the evolutionary perspective, stress can be caused by different factors,” she said. ” We tend to think of mental stress, but physical illness also causes a form of stress. When the body contracts a virus or bacteria it experiences stress, and signals to the immune system that the top priority is getting rid of the pathogen, while investing energy in long-term immunological memory is a second priority. (TPS)
