COVID-19 vaccines are enormously effective at warding off the deadly virus. Is there a way to make them even better?

To learn more, a major new UC San Francisco study is enlisting 600 Bay Area residents to investigate whether a range of predictors — such as age, sleep, stress and emotional wellbeing – might influence the power and persistence of our body’s defenses.

“We’re measuring factors that may lead to a more robust response, as well as factors that we believe will dampen, or weaken, the antibody response,” said UCSF psychiatry professor Elissa Epel, a co-investigator of the Building Optimal Antibodies Study project.

There might be ways to compensate for vaccine shortcomings, by enlisting emotional, behavioral or other interventions, according to the research team.

In a race against time, the U.S. is rushing to expand access to the precious COVID-19 vaccines. By Friday, about 17 percent of Americans had been inoculated.

While very good, they’re not perfect. A two-dose regimen of the Pfizer and Moderna vaccines prevents 92.6% of infections by two weeks after the second shot. The Johnson & Johnson shot is 72% effective.

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In some rare cases, people can still develop COVID-19 despite vaccination. The California Department of Public Health would not disclose the number of so-called “breakthrough cases” but said it is studying where and how frequently they occur.

Vaccines are designed to give the immune system a lasting memory of the viral components so that it can attack when confronted with the actual pathogen. It responds by deploying T cells, which identify and kill infected cells, and B cells, which produce the antibodies that bind to the virus so it can’t enter the cell.

But experience with other vaccines shows that not everyone responds equally well.  And our defenses fade at different rates. While new evidence shows that the Pfizer vaccine is effective for at least six months, its long-term durability is not known.

By measuring antibodies and T cells over time, “this study will help us understand the ‘time course’ of people’s responses,” said Aric Prather, an associate professor in the Department of Psychiatry and co-investigator of the UCSF study.

“What are the factors in our lives that can actually contribute, and create an enhanced response?” he said. “Or perhaps put people at risk, through a suboptimal response?”

For instance, age is known to play a role. The flu vaccine is about 70% to 90% effective in young adults – but less than 55% effective in the elderly, according to the U.S. Centers for Disease Control and Prevention. As we age, there’s a decline in the number, activity and diversity of the immune system’s protective T cells, a process scientists dub “immunosenescence.” By the age of 50, our T cell production is less than 10% of its peak.

Insufficient sleep is another predictor of how well our immune system responds to vaccination, according to Prather. Sleepless nights are proven to increase a person’s susceptibility to developing the common cold. It also mutes the body’s response to flu and hepatitis vaccinations.

“When people don’t get the sleep they need, they’re unable to kind of build the army of T cells that are important for protecting us against viruses,” said Prather.

Chronic stress is also known to impair the antibody response to a flu vaccine. Stress — such as the death of a loved one, financial loss, and parenting stress from school closures — can alter immune-regulating hormones.

“The adrenaline response to stress is helpful to us — but if it is too extreme during the time of vaccination, it can interfere with the molecular pathways of the immune response,” said Epel.

The team is making a specific appeal to include people of color, who have been burdened both by stress and discrimination, to see if these factors influence the response to the vaccine.

Obesity is linked to a dulled immune response to the COVID-19 virus. And vaccines for other infections often don’t work as well in overweight people, suggesting that the COVID-19 shot might not be fully protective.

A person’s genetics, or underlying health, could also play a role, according to UCSF’s Dr. Monica Gandhi. For instance, individuals who are highly immunocompromised may have a more blunted response.

All this could spell potential trouble for a COVID-19 vaccine.

Volunteers in the study will fill out questionnaires over a six-month period. They will be asked their mood, several times a day. They’ll also be asked questions such as: “What was the most stressful thing that happened to you today?” “How many hours did you sleep last night?”  “How did you feel your sleep quality was last night?”

Only unvaccinated people are eligible to participate. UCSF cannot provide the vaccine as part of the study, so volunteers must be inoculated elsewhere.

Their blood will be tested three different times: before the vaccination, one month after the second vaccination and six months after the second vaccination. They will be paid up to $300 for completing all aspects of the study.

In the blood, the scientists will measure the immune system response, counting levels of antibodies and T-cells. We don’t yet know exactly how many cells are needed to guarantee protection, said Epel. But it is possible to assess the overall vigor of an immune response.

The team will also measure the volunteers’ telomeres, the protective caps at the ends of chromosomes. Longer telomeres indicate a more youthful immune system, with cells that can go on to divide more robustly when exposed to antigens. Shorter telomere length has been linked to more severe infection with a cold virus, and poorer antibody response to flu vaccination.

This information will be kept private, according to the team. It will be “de-identified,” meaning it’s kept separate from a person’s name, phone number, or email, and no one outside of study staff will have access to records, including your employer.

The team hopes to follow the health of participants over time. This part of the study, which is optional, would collect information about medications, medical diseases and diagnoses of COVID-19 or other infections for the next five years.

“We’ll have all this information to be able to really understand someone’s immediate response, and the durability of that response, so we can correlate it with what is happening in people’s lives,” said Prather.

To learn more or to volunteer, go to: